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the prevalence of psoriasis is estimated to be 2&#46;3&#37; of the general population&#44; evenly distributed between the sexes&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">3</span></a> Approximately 30&#37; of these patients have moderate to severe forms of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">4</span></a> Moderate to severe psoriasis is currently managed with systemic therapies&#44; both conventional and biologic&#46; Clinical response and adverse effects are more variable with conventional systemic treatments and such therapy may not be acceptable to patients who demand more effective solutions&#46; The advent of biologic therapies has brought about a qualitative leap in the management of psoriasis&#44; marked by an improvement in response to treatment&#46; The biologic agents with regulatory approval in Europe can be divided into 4 groups according to the mechanism of action in each case&#58; tumor necrosis factor &#40;TNF-&#945;&#41; inhibitors &#40;etanercept&#44; adalimumab&#44; infliximab&#44; and certolizumab pegol&#41;&#59; interleukin &#40;IL&#41; 12&#47;23 inhibitors &#40;ustekinumab&#41;&#59; IL-17 inhibitors &#40;secukinumab&#44; ixekizumab&#44; and brodalumab&#41;&#59; and IL-23 inhibitors &#40;guselkumab and tildrakizumab&#41;&#46; The last two groups are the most recent&#46; At the time of writing&#44; certolizumab pegol&#44; brodalumab&#44; guselkumab&#44; and tildrakizumab have not obtained marketing approval in Spain&#46; The increase in the number of biologic drugs has led to an increase in the use of these therapies&#46; This&#44; together with the need to contain health expenditure&#44; has made it essential to consider the efficiency of these treatments&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Data from randomized clinical trials that directly compare 2 or more alternatives is the highest quality of evidence for deciding on the best possible treatment option&#46; When no direct comparisons are available&#44; however&#44; statistical methods&#44; such as network meta-analysis &#40;NMA&#41; can prove very useful&#46; The NMA technique allows us to synthesize the evidence available in studies in the literature &#40;obtained from a systematic review&#41; and use it to indirectly estimate the comparative efficacy of the different treatment options&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">One of the efficacy measures used to do this is the number of patients that must be treated to achieve a specific therapeutic objective&#46; The number needed to treat &#40;NNT&#41; is the number of patients that must receive treatment with a specific therapy to achieve or avoid a result or clinical event&#44; compared to the number needed to achieve the same result with an alternative treatment option or placebo&#46; This statistical parameter is a measure of absolute risk developed in the context of evidence-based medicine as a useful tool for making clinical decisions&#46; The range of values for NNT is from 1 to infinity&#46; The ideal value is 1&#44; since this indicates that every patient treated achieves the predefined clinical benefit&#59; after that&#44; the higher the NNT&#44; the less effective the intervention&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The advantage of NNT is that it provides clinicians who are taking therapeutic decisions with a more understandable concept of the effectiveness of a treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">8</span></a> Its use is increasing in dermatology&#44; and particularly psoriasis&#44; because very similar efficacy variables are used in the different clinical trials and the populations studied are very homogeneous&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The objective of this study was to determine the efficiency&#44; in terms of cost per NNT stratified by PASI response levels&#44; of the biologic therapies available in Spain for the treatment of moderate to severe plaque psoriasis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">Details of the methodology used for the original NMA and the systematic literature review have been published previously&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">9&#44;10</span></a> This NMA provides indirect comparisons for all the biologic treatments currently used in the management of moderate to severe plaque psoriasis in Spain&#46; The literature review included all the studies published in English between January 1990 and November 2015 and all the Phase <span class="elsevierStyleSmallCaps">II</span>&#44; <span class="elsevierStyleSmallCaps">III</span>&#44; and <span class="elsevierStyleSmallCaps">IV</span> randomized clinical trials carried out with each biologic agent&#46; The primary endpoint evaluated in the NMA was the PASI 75&#44; 90&#44; and 100 response &#40;the number of patients with a 75&#37;&#44; 90&#37; or 100&#37; reduction in their baseline PASI score&#41; at the end of the first 12 weeks for most biologic agents&#44; at 10 weeks in the case of infliximab&#44; and at 16 weeks for adalimumab&#46; In this analysis&#44; the NNT to achieve PASI 75&#44; 90 and 100 responses was calculated as the difference in response between the biologic agent and placebo at the end of the interval considered&#46; NNT was calculated as the inverse of the probability of response to biologic treatment minus the probability of response to placebo &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">NNT<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#47;&#40;probability of response with biologic treatment &#8211; probability of response with placebo&#41;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The cost in Spain of the biologic agents studied was based on the manufacturer&#39;s price &#40;MP&#41; for each pharmaceutical formulation as reported in the Bot Plus 2&#46;0 database published by the General Council of Official Spanish Pharmacists Associations &#40;CGCOF&#41;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">11</span></a> applying the corresponding discount for each drug in accordance with RDL 8&#47;2010<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">12</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">The resulting value was multiplied by the number of doses required for the first year of treatment as per the Summary of Product Characteristics for each drug&#44;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">13&#8211;18</span></a> adjusted for the calculations at 52 weeks &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; The cost of infliximab was calculated for an average patient weight of 80<span class="elsevierStyleHsp" style=""></span>kg&#44; since the dosage of this drug is dependent on the patient&#39;s weight&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">The cost per NNT for each agent was obtained by multiplying the cost of the drug in the first year of treatment by the NNT for each of the levels of PASI response considered&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">We also performed a sensitivity analysis that took into account only the number of injections during the response assessment period &#40;from 10 to 16 weeks depending on the drug&#41;&#46; The number of injections and the cost of treatment during this period&#44; are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a> show the cost per NNT to achieve a PASI 75&#44; 90&#44; or 100 response during the first year of treatment for each of the biologic therapies available in Spain that are used to treat moderate to severe plaque psoriasis&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">The cost per NNT of all the biologic therapies increased with each increment in PASI response &#40;75&#47;90&#47;100&#41;&#44; taking into account the first year of treatment&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">For the PASI 75 response&#44; the order from lowest to highest cost per NNT was as follows&#58; ixekizumab &#40;&#8364;18<span class="elsevierStyleHsp" style=""></span>741&#41; &#60;<span class="elsevierStyleHsp" style=""></span>ustekinumab 45<span class="elsevierStyleHsp" style=""></span>mg &#40;&#8364;19<span class="elsevierStyleHsp" style=""></span>187&#41; &#60;<span class="elsevierStyleHsp" style=""></span>ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#40;&#8364;20<span class="elsevierStyleHsp" style=""></span>503&#41; &#60;<span class="elsevierStyleHsp" style=""></span>secukinumab &#40;&#8364;20<span class="elsevierStyleHsp" style=""></span>619&#41; &#60;<span class="elsevierStyleHsp" style=""></span>infliximab &#40;&#8364;22<span class="elsevierStyleHsp" style=""></span>481&#41; &#60;<span class="elsevierStyleHsp" style=""></span>etanercept &#40;&#8364;25<span class="elsevierStyleHsp" style=""></span>320&#41; &#60;<span class="elsevierStyleHsp" style=""></span>adalimumab &#40;&#8364;25<span class="elsevierStyleHsp" style=""></span>567&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">For the PASI 90 response&#44; the order from lowest to highest cost per NNT was as follows&#58; ixekizumab &#40;&#8364;22<span class="elsevierStyleHsp" style=""></span>394&#41; &#60;<span class="elsevierStyleHsp" style=""></span>secukinumab &#40;&#8364; 27<span class="elsevierStyleHsp" style=""></span>280&#41; &#60;<span class="elsevierStyleHsp" style=""></span>ustekinumab 45<span class="elsevierStyleHsp" style=""></span>mg &#40;&#8364; 28<span class="elsevierStyleHsp" style=""></span>844&#41; &#60;<span class="elsevierStyleHsp" style=""></span>ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#40;&#8364; 29<span class="elsevierStyleHsp" style=""></span>249&#41; &#60;<span class="elsevierStyleHsp" style=""></span>infliximab &#40;&#8364;29<span class="elsevierStyleHsp" style=""></span>860&#41;&#41; &#60;<span class="elsevierStyleHsp" style=""></span>adalimumab &#40;&#8364; 44<span class="elsevierStyleHsp" style=""></span>610&#41; &#60;<span class="elsevierStyleHsp" style=""></span>etanercept &#40;&#8364;49<span class="elsevierStyleHsp" style=""></span>667&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">For the PASI 100 response&#44; the order from lowest to highest cost per NNT was as follows&#58; ixekizumab &#40;&#8364;39<span class="elsevierStyleHsp" style=""></span>070&#41; &#60;<span class="elsevierStyleHsp" style=""></span>secukinumab &#40;&#8364;57<span class="elsevierStyleHsp" style=""></span>098&#41; &#60;<span class="elsevierStyleHsp" style=""></span>infliximab &#40;&#8364;62<span class="elsevierStyleHsp" style=""></span>981&#41; &#60;<span class="elsevierStyleHsp" style=""></span>ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#40;&#8364;69<span class="elsevierStyleHsp" style=""></span>824&#41; &#60;<span class="elsevierStyleHsp" style=""></span>ustekinumab 45<span class="elsevierStyleHsp" style=""></span>mg &#40;&#8364;73<span class="elsevierStyleHsp" style=""></span>952&#41; &#60;<span class="elsevierStyleHsp" style=""></span>adalimumab &#40;&#8364;144<span class="elsevierStyleHsp" style=""></span>083&#41; &#60;<span class="elsevierStyleHsp" style=""></span>etanercept &#40;&#8364;195<span class="elsevierStyleHsp" style=""></span>529&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The sensitivity analysis shows the cost per NNT for each drug for the period during which the PASI was actually measured&#58; week 10&#44; 12&#44; or 16 depending on the drug &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>&#44; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">For the PASI 75 response&#44; the order from lowest to highest cost per NNT was as follows&#58; ustekinumab 45<span class="elsevierStyleHsp" style=""></span>mg &#40;&#8364;6607&#41; &#60;<span class="elsevierStyleHsp" style=""></span>adalimumab &#40;&#8364;6801&#41; &#60;<span class="elsevierStyleHsp" style=""></span>etanercept &#40;&#8364;7791&#41; &#60;<span class="elsevierStyleHsp" style=""></span>infliximab &#40;&#8364;8430&#41; &#60;<span class="elsevierStyleHsp" style=""></span>ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#40;&#8364;8663&#41; &#60;<span class="elsevierStyleHsp" style=""></span>ixekizumab &#40;&#8364;8819&#41; &#60;<span class="elsevierStyleHsp" style=""></span>secukinumab &#40;&#8364;9178&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">For the PASI 90 response&#44; the order from lowest to highest cost per NNT was as follows&#58; ustekinumab 45<span class="elsevierStyleHsp" style=""></span>mg &#40;&#8364;8742&#41; &#60;<span class="elsevierStyleHsp" style=""></span>adalimumab &#40;&#8364;9702&#41; &#60;<span class="elsevierStyleHsp" style=""></span>ixekizumab &#40;&#8364;10<span class="elsevierStyleHsp" style=""></span>538&#41; &#60;<span class="elsevierStyleHsp" style=""></span>infliximab &#40;&#8364;11<span class="elsevierStyleHsp" style=""></span>198&#41; &#60;<span class="elsevierStyleHsp" style=""></span>secukinumab &#40;&#8364;11 621&#41; &#60;<span class="elsevierStyleHsp" style=""></span>ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#40;&#8364;13<span class="elsevierStyleHsp" style=""></span>018&#41; &#60;<span class="elsevierStyleHsp" style=""></span>etanercept &#40;&#8364;13<span class="elsevierStyleHsp" style=""></span>593&#41;&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">For the PASI 100 response&#44; the order from lowest to highest cost per NNT was as follows&#58; ustekinumab 45<span class="elsevierStyleHsp" style=""></span>mg &#40;&#8364;18<span class="elsevierStyleHsp" style=""></span>297&#41; &#60;<span class="elsevierStyleHsp" style=""></span>ixekizumab &#40;&#8364;18<span class="elsevierStyleHsp" style=""></span>396&#41; &#60;<span class="elsevierStyleHsp" style=""></span>secukinumab &#40;&#8364;22<span class="elsevierStyleHsp" style=""></span>575&#41; &#60;<span class="elsevierStyleHsp" style=""></span>adalimumab &#40;&#8364;23<span class="elsevierStyleHsp" style=""></span>161&#41; &#60;<span class="elsevierStyleHsp" style=""></span>infliximab &#40;&#8364;23<span class="elsevierStyleHsp" style=""></span>618&#41; &#60;<span class="elsevierStyleHsp" style=""></span>ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#40;&#8364;33<span class="elsevierStyleHsp" style=""></span>378&#41; &#60;<span class="elsevierStyleHsp" style=""></span>etanercept &#40;&#8364;43<span class="elsevierStyleHsp" style=""></span>905&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">In recent years&#44; the advent of biologic therapies has led to improved clinical outcomes in patients with moderate to severe plaque psoriasis&#46; However&#44; the increasing expenditure on these drugs makes it necessary to analyze the efficiency of the available treatments&#46; Our findings show that the more effective drugs are also the most efficient&#46; The order from lowest to highest cost per NNT of the biologic agents studied evidences the greater efficiency of the therapies with more recent mechanisms of action&#44; such as the IL-17 and IL-12&#47;23 inhibitors&#44; which obtained higher response levels than TNF-&#945; inhibitors in clinical trials&#46; Moreover&#44; the cost per NNT increases when the treatment objective requires more complete skin clearance &#40;a higher PASI response level&#41;&#46; However&#44; given the overlapping credible intervals for most of the biologic agents and PASI response levels studied&#44; these sequences are only indicative and the differences observed are not statistically significant&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">This is the first study to compare the cost per NNT of all the biologic treatments currently available in Spain for the treatment of moderate to severe plaque psoriasis&#46; The more recently developed biologic agents &#40;certolizumab pegol&#44; brodalumab&#44; guselkumab&#44; and tildrakizumab&#41; were not included in this study for 2 reasons&#58; first&#44; because the results of clinical trials were not available when the NMA was performed&#59; and&#44; second&#44; because the official price had not been established&#46; However NNT values for these drugs have since been published&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">20&#8211;22</span></a> Our findings are consistent with those of earlier studies&#44; which reported very similar NNT values for biologic therapies&#44; likewise obtained through indirect comparison methods&#44; such as NMA&#44;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">22&#44;23</span></a> and similar sequences from lowest to highest cost per NNT&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">10&#44;19&#44;24&#8211;26</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">While a PASI 75 response has traditionally been considered the treatment objective of reference in this setting&#44;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">27&#44;28</span></a> patients who achieve a PASI 90 response or higher have a score of 0 to 1 on the Dermatology Quality of Life Index &#40;DLQI&#41; in a significantly higher percentage than those whose response is PASI 75&#46; This score of 0 to 1 on the DLQI scale signifies that the disease has a zero or minimal impact on the patient&#39;s quality of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">29&#8211;31</span></a> This improvement in patient quality of life arising from an improved response to treatment&#44; together with the availability of new therapies that can achieve a PASI 90 response in a sizable percentage of patients&#44; has led to a PASI 90 or higher response being considered the most important treatment objective&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">32&#8211;34</span></a> It is interesting to note that&#44; for most of the biologic therapies&#44; the cost increase per NNT required to achieve a PASI 90 as compared to a PASI 75 response is less than the cost increase per NNT to achieve a PASI 100 compared to a PASI 90 response&#46; This is a consequence of the skin clearance results achieved by the biologic agents during clinical development&#58; the newer biologics achieved PASI 90 responses in a higher proportion of patients and also achieved higher PASI 100 response rates than those achieved by earlier biologic treatments&#44; such as the TNF-&#945; inhibitors&#46; These differences are reflected in the cost per NNT results reported in this study&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Analysis of cost per NNT differs from complete economic evaluations&#44; such as cost-effectiveness analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">35</span></a> That methodology&#44; endorsed by scientific societies and commonly used to assess health technologies&#44; models outcome and cost variables over a considerable period&#44; taking into account not only the pharmacological cost of therapies but also the consumption of other types of resources involved in the management of the disease&#44; an important consideration when making decisions on how to allocate the health care budget&#46; However&#44; calculating the cost per unit of clinical efficacy &#40;NNT&#41; may be another approach that can provide very comprehensible information for clinicians and others involved in making health care decisions&#46; Cost per NNT is not&#44; however&#44; a useful measure for establishing a threshold to inform decisions on how much should reasonably be invested in achieving a health outcome&#44; unlike cost-effectiveness analysis&#44; which does provide information that can inform such decisions&#46; It may&#44; therefore&#44; be useful to have both methods in order to provide information to inform different types of decisions&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">One of the limitations of this study is the lack of data from clinical trials that directly compare the different drugs&#46; This lack of data led us to combine the evidence available and to carry out indirect comparisons by means of an NMA of all the studies on the biologic therapies available in Spain published in the current literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">9&#44;10</span></a> Our NMA was based on a systematic literature review of clinical trials published before the end of November 2015 and&#44; given the high level of activity in this area&#44; other studies using a similar methodology &#40;NMA&#41; and including clinical trials after that date have been carried out&#46; However&#44; the findings reported by the later NMA corroborate the results of our study&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">20&#44;26</span></a> The NNT obtained in our NMA were used to calculate the cost of the first year of treatment&#46; In the methodology used&#44; it was assumed that all the drugs studied maintained the efficacy observed in the short term &#40;during the induction period&#41; through to the end of the first year of treatment&#46; This approach provides the best possible approximation of the actual situation as we found no clinical trials with homogeneous designs providing data on the maintenance of response over a longer period to facilitate indirect comparisons &#40;and the calculation of cost per NNT&#41;&#46; Basing the analysis on the assumption that the response was maintained over a longer period than the induction phase is not a new approach&#58; the same assumption has been made by the authors of most studies that compare the cost of biologic therapies over longer periods&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">19&#44;24&#44;25</span></a> We also performed a sensitivity analysis including only the data from the period during which the PASI response was assessed in the clinical trials included in the NMA&#46; In that analysis&#44; ustekinumab was the most efficient treatment for all levels of PASI response&#44; both because of the clinical response obtained and the dosage regimen used&#46; The cost per NNT of the new IL-17 inhibitors decreases with each increment in PASI response &#40;75&#47;90&#47;100&#41;&#46; Another limitation of this study is the use of the manufacturer&#39;s catalogue price &#40;MP&#41; to calculate the cost of treatment&#46; In the current Spanish system&#44; the official MP may be discounted by the vendor to ensure that the treatment is covered by the National Health System &#40;giving rise to a subsidized price&#41;&#46; This reduced price more closely reflects the actual cost of the drug&#46; It is&#44; however&#44; extremely difficult to obtain precise data on the actual prices paid&#46; Moreover&#44; the final price of biologic agents in Spain is also subject to additional discounts in hospitals&#44; giving rise to even greater variability&#46; For all these reasons&#44; we opted to base our analysis on the MP&#46; This study provides information on the efficiency&#44; in terms of cost per NNT&#44; of the biologic treatments currently available in Spain for the treatment of moderate to severe plaque psoriasis&#44; stratified by level of treatment response &#40;PASI 75&#44; 90 and 100&#41;&#46; The results show that the more effective biologic treatments are also more efficient&#46; Of the therapies studied&#44; ixekizumab was the biologic agent with the lowest cost per NNT and&#44; therefore&#44; the most efficient treatment for moderate to severe plaque psoriasis at all PASI response levels over a 1-year treatment period&#46; Ustekinumab was the most efficient treatment when only the response assessment period was taken into account &#40;10 to 16 weeks depending on the drug&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Funding</span><p id="par0140" class="elsevierStylePara elsevierViewall">This study was funded by Eli Lilly and Company&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflicts of Interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">P&#46; de la Cueva has participated in clinical trials or received consultancy or lecture fees from Abbvie&#44; Almirall&#44; Biogen&#44; Boehringer-Ingelhaim&#44; Celgene&#44; Gebro&#44; Janssen&#44; Leo Pharma&#44; MSD&#44; Novartis&#44; Pfizer&#44; Lilly&#44; Sanofi&#44; and UDC Pharma&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">M&#46; Nu&#241;ez&#44; T&#46; Huete&#44; JA Sacrist&#225;n&#44; S&#46; Hartz and T&#46; Dilla are employees of Eli Lilly and Company&#46;</p></span></span>"
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    "fechaRecibido" => "2018-07-04"
    "fechaAceptado" => "2018-10-01"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1149014"
          "palabras" => array:5 [
            0 => "Biologic therapy"
            1 => "Effectiveness"
            2 => "Psoriasis Area and Severity Index"
            3 => "Induction"
            4 => "Cost-effectiveness"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1149015"
          "palabras" => array:5 [
            0 => "Terapia biol&#243;gica"
            1 => "Efectividad"
            2 => "<span class="elsevierStyleItalic">Psoriasis Area and Severity Index</span>"
            3 => "Inducci&#243;n"
            4 => "Coste-efectividad"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Psoriasis is a chronic inflammatory skin disease with an estimated prevalence in Spain of 2&#46;3&#37; of the population&#46; Approximately 30&#37; of patients have moderate-to-severe forms&#46; Treatment with biologic agents is proving to be a step forward in the management of the disease&#44; although these treatments are very expensive&#46; The objective of this study was to determine the efficiency&#44; in terms of cost per number needed to treat &#40;NNT&#41;&#44; of the biologic drugs available in Spain for the treatment of moderate to severe plaque psoriasis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">NNT data were obtained from a network meta-analysis that included all randomized clinical trials of biologic drugs sold in Spain&#46; The cost of each treatment was calculated based on the approved dosage for the first year of treatment&#44; as indicated in the Summary of Product Characteristics&#46; These data were used to calculate the cost per NNT of the drugs for various PASI scores &#40;75&#44; 90&#44; and 100&#41;&#46; A sensitivity analysis was performed taking into consideration only the PASI-response measurement time &#40;after 10&#44; 12&#44; or 16 weeks&#44; depending on the drug&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The order of efficiency&#44; from most to least efficient&#44; in the case of a PASI 75 response was ixekizumab &#62; ustekinumab 45<span class="elsevierStyleHsp" style=""></span>mg &#62; ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#62; secukinumab &#62; infliximab &#62; etanercept &#62; adalimumab&#46; The order for PASI 90 was ixekizumab &#62;secukinumab &#62;ustekinumab 45<span class="elsevierStyleHsp" style=""></span>mg &#62; ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#62; infliximab &#62; adalimumab &#62; etanercept&#46; The order for PASI 100 was ixekizumab &#62; secukinumab &#62; infliximab &#62; ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#62; ustekinumab 45<span class="elsevierStyleHsp" style=""></span>mg &#62; adalimumab &#62; etanercept&#46; The sensitivity analysis showed some changes in the order&#44; depending on the response-assessment period&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The findings show a link between the efficacy of the biologic therapies available in Spain for the treatment of moderate-to-severe plaque psoriasis and their efficiency&#46; Ixekizumab had the lowest cost per NNT for all PASI-response scores &#40;75&#44; 90&#44; and 100&#41; during the first year of treatment&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background and objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La psoriasis es una enfermedad inflamatoria cr&#243;nica de la piel cuya prevalencia en Espa&#241;a se estima en el 2&#44;3&#37; de la poblaci&#243;n y en la que alrededor del 30&#37; de los pacientes tienen formas moderadas a graves&#46; El tratamiento con agentes biol&#243;gicos est&#225; suponiendo un avance en el manejo de la enfermedad&#44; aunque tambi&#233;n representa un reto econ&#243;mico&#46; El objetivo de este estudio es determinar la eficiencia&#44; en t&#233;rminos de coste por n&#250;mero necesario a tratar &#40;NNT&#41;&#44; de las terapias biol&#243;gicas disponibles en Espa&#241;a para el tratamiento de la psoriasis en placas moderada a grave&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Los datos de NNT se obtuvieron de un metaan&#225;lisis en red que inclu&#237;a todos los ensayos cl&#237;nicos aleatorizados con medicamentos biol&#243;gicos comercializados en Espa&#241;a&#46; Los costes de cada terapia se calcularon seg&#250;n las posolog&#237;as aprobadas en las fichas t&#233;cnicas para el primer a&#241;o de tratamiento&#46; A partir de estos datos se calcul&#243; el coste por NNT de los f&#225;rmacos para los distintos niveles de PASI &#40;75&#44; 90 y 100&#41;&#46; Se realiz&#243; un an&#225;lisis de sensibilidad considerando solamente el periodo de medici&#243;n de la respuesta PASI &#40;de 10 a 16 semanas&#41; seg&#250;n el tratamiento&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Para la respuesta PASI 75&#44; el orden de terapias de mayor a menor eficiencia es ixekizumab &#62; ustekinumab 45<span class="elsevierStyleHsp" style=""></span>mg &#62; ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#62; secukinumab &#62; infliximab &#62; etanercept &#62; adalimumab&#46; Para la respuesta PASI 90&#44; el orden es ixekizumab &#62; secukinumab &#62; ustekinumab 45<span class="elsevierStyleHsp" style=""></span>mg &#62; ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#62; infliximab &#62; adalimumab &#62; etanercept&#46; Para la respuesta PASI 100 el orden es ixekizumab &#62; secukinumab &#62; infliximab &#62; ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#62; ustekinumab 45<span class="elsevierStyleHsp" style=""></span>mg &#62; adalimumab &#62; etanercept&#46; El an&#225;lisis de sensibilidad mostr&#243; alg&#250;n cambio en el orden de las secuencias para el periodo de evaluaci&#243;n de la respuesta&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este an&#225;lisis muestra una relaci&#243;n entre la eficacia de los tratamientos biol&#243;gicos disponibles en Espa&#241;a para el tratamiento de la psoriasis en placas moderada a grave y su eficiencia&#44; siendo ixekizumab el que mostr&#243; un menor coste por NNT en todos los niveles de respuesta PASI alcanzados &#40;75&#44; 90 y 100&#41; para el primer a&#241;o de tratamiento&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Antecedentes y objetivos"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; N&#250;&#241;ez M&#44; Huete T&#44; de la Cueva P&#44; Sacrist&#225;n JA&#44; Hartz S&#44; Dilla T&#46; Evaluaci&#243;n de la eficiencia de los tratamientos biol&#243;gicos en la psoriasis moderada a grave en Espa&#241;a&#58; an&#225;lisis de coste por n&#250;mero necesario a tratar &#40;NNT&#41;&#46; Actas Dermosifiliogr&#46; 2019&#59;110&#58;546&#8211;553&#46;</p>"
      ]
    ]
    "multimedia" => array:8 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1285
            "Ancho" => 2500
            "Tamanyo" => 122176
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Cost per NNT for the first year of treatment with biologic therapies&#44; stratified by response level &#40;PASI 75&#44; 90 and 100&#41;&#46; The error bars represent credible intervals &#40;2&#46;5&#37;&#8722;97&#46;5&#37;&#41;&#46; Q2W indicates every 2 weeks&#59; Q1W&#44; weekly&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1479
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            "Tamanyo" => 137731
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Cost per NNT for the period in which response was actually measured &#40;from 10 to 16 weeks depending on the drug&#41;&#44; stratified by response level &#40;PASI 75&#44; 90 and 100&#41;&#46; The error bars represent credible intervals &#40;2&#46;5&#37; -97&#44; 5&#37;&#41;&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; EOW&#44; every other week&#59; CrI&#44; credible interval&#59; NNT&#44; number needed to treat&#59; PASI&#44; Psoriasis Area and Severity Index&#59; QIW&#44; weekly&#59; Q2W&#44; every 2 weeks&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NNT PASI 75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CrI 2&#46;5&#37;-97&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NNT PASI 90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CrI 2&#46;5&#37;-97&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NNT PASI 100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CrI 2&#46;5&#37;-97&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ixekizumab 80<span class="elsevierStyleHsp" style=""></span>mg Q2W&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;13-1&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;26-1&#46;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;93-3&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Secukinumab 300 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;21-1&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;47-2&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;64-4&#46;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustekinumab 45 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;37-1&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;85-2&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;04-8&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustekinumab 90 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;30-1&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;68-2&#46;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">3&#46;40-7&#46;01&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Adalimumab 80&#47;40&#160;mg EOW&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;92&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;60-2&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">6&#46;42-17&#46;85&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Etanercept 50&#160;mg QIW&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#46;70-54&#46;87&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Infliximab 5 mg&#47;kg&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;44-2&#46;14&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#46;67&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;53-5&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2114501.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">NNT per PASI Response Level With Placebo as the Comparator &#40;CrI 2&#46;5-97&#46;5&#37;&#41;&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose per Pen or Vial&#44; mg&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MP per Pen or Vial After Discount&#44; &#8364;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RDL 8&#47;2010 discount&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Ixekizumab&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1010&#46;00&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">934&#46;25&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Secukinumab&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1143&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">528&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustekinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">2747&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2541&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustekinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3100&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2867&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adalimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1028&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">475&#46;58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanercept<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">676&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">169&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Infliximab<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">536&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">536&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2114502.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Approved biosimilars already exist for these drugs&#46; The price of these on PVL BOT Plus ranges from &#8364;676&#46;29 to &#8364;760&#46;84 for etanercept biosimilars and from &#8364;439&#46;75 to 482&#46;65 for infliximab biosimilars&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Official Manufacturer&#39;s Price &#40;MP&#41; for the Biologic Agents&#44; Showing Applicable Discounts&#44; Number of Pens or Vials per Pack&#44; and Dose per Pen or Vial&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Mean patient weight&#58; 80<span class="elsevierStyleHsp" style=""></span>kg&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dosage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No&#46; of injections per year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Annual Cost&#44; &#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ixekizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">160&#160;mg in wk 0&#44; followed by 80<span class="elsevierStyleHsp" style=""></span>mg in wks 2&#44; 4&#44; 6&#44; 8&#44; 10 and 12&#44; and then a maintenance dose of 80&#160;mg every 4 wks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15<span class="elsevierStyleHsp" style=""></span>882&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Secukinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300&#160;mg in wks 0&#44; 1&#44; 2 and 3 followed by 300<span class="elsevierStyleHsp" style=""></span>mg monthly from wk 4 onwards&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15<span class="elsevierStyleHsp" style=""></span>861&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustekinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">In patients weighing &#60; 100&#160;kg&#44; 45<span class="elsevierStyleHsp" style=""></span>mg followed by a second dose of 45&#160;mg 4 wks later and then 45&#160;mg every 12 wks thereafter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12<span class="elsevierStyleHsp" style=""></span>707&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">In patients weighing &#62; 100&#160;kg&#44; 90&#160;mg followed by an additional dose of 90&#160;mg 4 wks later and then 90&#160;mg every 12 wks thereafter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14<span class="elsevierStyleHsp" style=""></span>338&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adalimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80&#160;mg&#44; followed by 40&#160;mg every 2 wks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13<span class="elsevierStyleHsp" style=""></span>316&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanercept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#160;mg twice weekly for 12 wks&#44; followed by a maintenance regimen of 50&#160;mg&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10<span class="elsevierStyleHsp" style=""></span>821&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Infliximab<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg&#47;kg followed by additional doses of 5 mg&#47;kg at wks 2 and 6 and every 8 wks thereafter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17<span class="elsevierStyleHsp" style=""></span>161&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2114505.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Dosage&#44; Number of Injections&#44; and Cost per Patient for the First Year of Treatment&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Mean patient weight&#58; 80<span class="elsevierStyleHsp" style=""></span>kg&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Time to Response&#44; wks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No&#46; of Injections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cost&#44; &#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ixekizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7474&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Secukinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7402&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustekinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5083&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5735&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adalimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4756&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanercept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4058&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Infliximab<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6435&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Data on Actual Response Used in Sensitivity Analysis&#44; With Number of Injections During the Assessment Period and Cost per Patient&#46;</p>"
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          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; EOW&#44; every other week&#59; CrI&#44; credible interval&#59; NNT&#44; number needed to treat&#59; PASI&#44; Psoriasis Area and Severity Index&#59; QIW&#44; weekly&#59; Q2W&#44; every 2 weeks&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Cost per NNT&#44; &#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Cost per NNT&#44; &#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Cost per NNT&#44; &#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PASI 75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CrI 2&#46;5&#37;-97&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PASI 90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CrI 2&#46;5&#37;-97&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PASI 100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CrI <a class="elsevierStyleCrossRef" href="#bib0185">2</a>&#46;5&#37;-97&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ixekizumab 80<span class="elsevierStyleHsp" style=""></span>mg Q2W&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18<span class="elsevierStyleHsp" style=""></span>741&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17<span class="elsevierStyleHsp" style=""></span>947-19<span class="elsevierStyleHsp" style=""></span>853&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22<span class="elsevierStyleHsp" style=""></span>394&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20<span class="elsevierStyleHsp" style=""></span>012-25<span class="elsevierStyleHsp" style=""></span>570&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39<span class="elsevierStyleHsp" style=""></span>070&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30<span class="elsevierStyleHsp" style=""></span>653-50<span class="elsevierStyleHsp" style=""></span>664&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Secukinumab 300 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20<span class="elsevierStyleHsp" style=""></span>619&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19<span class="elsevierStyleHsp" style=""></span>191-22<span class="elsevierStyleHsp" style=""></span>364&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27<span class="elsevierStyleHsp" style=""></span>280&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23<span class="elsevierStyleHsp" style=""></span>315-32<span class="elsevierStyleHsp" style=""></span>356&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57<span class="elsevierStyleHsp" style=""></span>098&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41<span class="elsevierStyleHsp" style=""></span>872-77<span class="elsevierStyleHsp" style=""></span>241&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustekinumab 45 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19<span class="elsevierStyleHsp" style=""></span>187&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17<span class="elsevierStyleHsp" style=""></span>408-21<span class="elsevierStyleHsp" style=""></span>728&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28<span class="elsevierStyleHsp" style=""></span>844&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23<span class="elsevierStyleHsp" style=""></span>507-36<span class="elsevierStyleHsp" style=""></span>087&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73<span class="elsevierStyleHsp" style=""></span>952&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51<span class="elsevierStyleHsp" style=""></span>334-106<span class="elsevierStyleHsp" style=""></span>354&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustekinumab 90 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20<span class="elsevierStyleHsp" style=""></span>503&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18<span class="elsevierStyleHsp" style=""></span>639-22<span class="elsevierStyleHsp" style=""></span>940&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29<span class="elsevierStyleHsp" style=""></span>249&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24<span class="elsevierStyleHsp" style=""></span>087-36<span class="elsevierStyleHsp" style=""></span>417&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69<span class="elsevierStyleHsp" style=""></span>824&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48<span class="elsevierStyleHsp" style=""></span>748-100<span class="elsevierStyleHsp" style=""></span>506&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adalimumab 80&#47;40&#160;mg EOW&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25<span class="elsevierStyleHsp" style=""></span>567&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21<span class="elsevierStyleHsp" style=""></span>306-31<span class="elsevierStyleHsp" style=""></span>427&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44<span class="elsevierStyleHsp" style=""></span>610&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32<span class="elsevierStyleHsp" style=""></span>359-62<span class="elsevierStyleHsp" style=""></span>054&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">144<span class="elsevierStyleHsp" style=""></span>083&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85<span class="elsevierStyleHsp" style=""></span>491-237<span class="elsevierStyleHsp" style=""></span>697&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanercept 50&#160;mg QIW&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25<span class="elsevierStyleHsp" style=""></span>320&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15<span class="elsevierStyleHsp" style=""></span>365-45<span class="elsevierStyleHsp" style=""></span>988&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49<span class="elsevierStyleHsp" style=""></span>667&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug</th><th class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Cost per NNT&#44; &#8364;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Cost per NNT&#44; &#8364;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Cost per NNT&#44; &#8364;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PASI 75&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CrI 2&#46;5&#37;-97&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PASI 90&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CrI 2&#46;5&#37;-97&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PASI 100&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CrI 2&#46;5&#37;-97&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Ixekizumab 80<span class="elsevierStyleHsp" style=""></span>mg Q2W&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8819&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Secukinumab 300 mg&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9178&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8<span class="elsevierStyleHsp" style=""></span>660-9918&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11<span class="elsevierStyleHsp" style=""></span>621&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10<span class="elsevierStyleHsp" style=""></span>140-13<span class="elsevierStyleHsp" style=""></span>696&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22<span class="elsevierStyleHsp" style=""></span>575&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16<span class="elsevierStyleHsp" style=""></span>950-30<span class="elsevierStyleHsp" style=""></span>347&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustekinumab 45 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6607&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6150-7166&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8742&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7471-10<span class="elsevierStyleHsp" style=""></span>369&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18<span class="elsevierStyleHsp" style=""></span>297&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13<span class="elsevierStyleHsp" style=""></span>418-24<span class="elsevierStyleHsp" style=""></span>752&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustekinumab 90 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8660&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7857-9807&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13<span class="elsevierStyleHsp" style=""></span>018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10<span class="elsevierStyleHsp" style=""></span>610-16<span class="elsevierStyleHsp" style=""></span>287&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33<span class="elsevierStyleHsp" style=""></span>378&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23<span class="elsevierStyleHsp" style=""></span>169-48<span class="elsevierStyleHsp" style=""></span>002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adalimumab 80&#47;40&#160;mg EOW&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6801&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6183-7609&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9702&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23<span class="elsevierStyleHsp" style=""></span>161&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Etanercept 50&#160;mg QIW&nbsp;\t\t\t\t\t\t\n
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Vol. 110. Núm. 7.
Páginas 546-553 (septiembre 2019)
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Vol. 110. Núm. 7.
Páginas 546-553 (septiembre 2019)
Original Article
Acceso a texto completo
A Cost-per-Number Needed to Treat Analysis Assessing the Efficiency of Biologic Drugs in Moderate to Severe Plaque Psoriasis
Evaluación de la eficiencia de los tratamientos biológicos en la psoriasis moderada a grave en España: análisis de coste por número necesario a tratar (NNT)
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M. Núñeza,
Autor para correspondencia
nunez_mercedes@lilly.com

Corresponding author.
, T. Huetea, P. de la Cuevab, J.A. Sacristána, S. Hartzc, T. Dillaa
a Eli Lilly and Company, Madrid, Spain
b Servicio de Dermatología, Hospital Universitario Infanta Leonor, Madrid, Spain
c Eli Lilly and Company, Surrey, United Kingdom
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Tablas (6)
Table 1. NNT per PASI Response Level With Placebo as the Comparator (CrI 2.5-97.5%).
Table 2. Official Manufacturer's Price (MP) for the Biologic Agents, Showing Applicable Discounts, Number of Pens or Vials per Pack, and Dose per Pen or Vial.
Table 3. Dosage, Number of Injections, and Cost per Patient for the First Year of Treatment.
Table 4. Data on Actual Response Used in Sensitivity Analysis, With Number of Injections During the Assessment Period and Cost per Patient.
Table 5. Cost per NNT in the First Year of Treatment.
Table 6. Cost per NNT During the Treatment Response Assessment Period.
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Abstract
Background and objectives

Psoriasis is a chronic inflammatory skin disease with an estimated prevalence in Spain of 2.3% of the population. Approximately 30% of patients have moderate-to-severe forms. Treatment with biologic agents is proving to be a step forward in the management of the disease, although these treatments are very expensive. The objective of this study was to determine the efficiency, in terms of cost per number needed to treat (NNT), of the biologic drugs available in Spain for the treatment of moderate to severe plaque psoriasis.

Methods

NNT data were obtained from a network meta-analysis that included all randomized clinical trials of biologic drugs sold in Spain. The cost of each treatment was calculated based on the approved dosage for the first year of treatment, as indicated in the Summary of Product Characteristics. These data were used to calculate the cost per NNT of the drugs for various PASI scores (75, 90, and 100). A sensitivity analysis was performed taking into consideration only the PASI-response measurement time (after 10, 12, or 16 weeks, depending on the drug).

Results

The order of efficiency, from most to least efficient, in the case of a PASI 75 response was ixekizumab > ustekinumab 45mg > ustekinumab 90mg > secukinumab > infliximab > etanercept > adalimumab. The order for PASI 90 was ixekizumab >secukinumab >ustekinumab 45mg > ustekinumab 90mg > infliximab > adalimumab > etanercept. The order for PASI 100 was ixekizumab > secukinumab > infliximab > ustekinumab 90mg > ustekinumab 45mg > adalimumab > etanercept. The sensitivity analysis showed some changes in the order, depending on the response-assessment period.

Conclusions

The findings show a link between the efficacy of the biologic therapies available in Spain for the treatment of moderate-to-severe plaque psoriasis and their efficiency. Ixekizumab had the lowest cost per NNT for all PASI-response scores (75, 90, and 100) during the first year of treatment.

Keywords:
Biologic therapy
Effectiveness
Psoriasis Area and Severity Index
Induction
Cost-effectiveness
Resumen
Antecedentes y objetivos

La psoriasis es una enfermedad inflamatoria crónica de la piel cuya prevalencia en España se estima en el 2,3% de la población y en la que alrededor del 30% de los pacientes tienen formas moderadas a graves. El tratamiento con agentes biológicos está suponiendo un avance en el manejo de la enfermedad, aunque también representa un reto económico. El objetivo de este estudio es determinar la eficiencia, en términos de coste por número necesario a tratar (NNT), de las terapias biológicas disponibles en España para el tratamiento de la psoriasis en placas moderada a grave.

Métodos

Los datos de NNT se obtuvieron de un metaanálisis en red que incluía todos los ensayos clínicos aleatorizados con medicamentos biológicos comercializados en España. Los costes de cada terapia se calcularon según las posologías aprobadas en las fichas técnicas para el primer año de tratamiento. A partir de estos datos se calculó el coste por NNT de los fármacos para los distintos niveles de PASI (75, 90 y 100). Se realizó un análisis de sensibilidad considerando solamente el periodo de medición de la respuesta PASI (de 10 a 16 semanas) según el tratamiento.

Resultados

Para la respuesta PASI 75, el orden de terapias de mayor a menor eficiencia es ixekizumab > ustekinumab 45mg > ustekinumab 90mg > secukinumab > infliximab > etanercept > adalimumab. Para la respuesta PASI 90, el orden es ixekizumab > secukinumab > ustekinumab 45mg > ustekinumab 90mg > infliximab > adalimumab > etanercept. Para la respuesta PASI 100 el orden es ixekizumab > secukinumab > infliximab > ustekinumab 90mg > ustekinumab 45mg > adalimumab > etanercept. El análisis de sensibilidad mostró algún cambio en el orden de las secuencias para el periodo de evaluación de la respuesta.

Conclusiones

Este análisis muestra una relación entre la eficacia de los tratamientos biológicos disponibles en España para el tratamiento de la psoriasis en placas moderada a grave y su eficiencia, siendo ixekizumab el que mostró un menor coste por NNT en todos los niveles de respuesta PASI alcanzados (75, 90 y 100) para el primer año de tratamiento.

Palabras clave:
Terapia biológica
Efectividad
Psoriasis Area and Severity Index
Inducción
Coste-efectividad
Texto completo
Background

Psoriasis is a chronic inflammatory skin disease. Its most common manifestation is the appearance of erythematous plaques on the skin. The condition has negative repercussions on the patients’ physical and emotional wellbeing and quality of life.1 Dermatologists generally assess the severity of psoriasis by measuring the percentage of total body surface area (BSA) affected or by using the Psoriasis Area Severity Index (PASI). It is generally accepted that patients with a greater than 10% affected BSA or a PASI score above 10 have moderate to severe psoriasis.2

In Spain, the prevalence of psoriasis is estimated to be 2.3% of the general population, evenly distributed between the sexes.3 Approximately 30% of these patients have moderate to severe forms of the disease.4 Moderate to severe psoriasis is currently managed with systemic therapies, both conventional and biologic. Clinical response and adverse effects are more variable with conventional systemic treatments and such therapy may not be acceptable to patients who demand more effective solutions. The advent of biologic therapies has brought about a qualitative leap in the management of psoriasis, marked by an improvement in response to treatment. The biologic agents with regulatory approval in Europe can be divided into 4 groups according to the mechanism of action in each case: tumor necrosis factor (TNF-α) inhibitors (etanercept, adalimumab, infliximab, and certolizumab pegol); interleukin (IL) 12/23 inhibitors (ustekinumab); IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab); and IL-23 inhibitors (guselkumab and tildrakizumab). The last two groups are the most recent. At the time of writing, certolizumab pegol, brodalumab, guselkumab, and tildrakizumab have not obtained marketing approval in Spain. The increase in the number of biologic drugs has led to an increase in the use of these therapies. This, together with the need to contain health expenditure, has made it essential to consider the efficiency of these treatments.5

Data from randomized clinical trials that directly compare 2 or more alternatives is the highest quality of evidence for deciding on the best possible treatment option. When no direct comparisons are available, however, statistical methods, such as network meta-analysis (NMA) can prove very useful. The NMA technique allows us to synthesize the evidence available in studies in the literature (obtained from a systematic review) and use it to indirectly estimate the comparative efficacy of the different treatment options.6

One of the efficacy measures used to do this is the number of patients that must be treated to achieve a specific therapeutic objective. The number needed to treat (NNT) is the number of patients that must receive treatment with a specific therapy to achieve or avoid a result or clinical event, compared to the number needed to achieve the same result with an alternative treatment option or placebo. This statistical parameter is a measure of absolute risk developed in the context of evidence-based medicine as a useful tool for making clinical decisions. The range of values for NNT is from 1 to infinity. The ideal value is 1, since this indicates that every patient treated achieves the predefined clinical benefit; after that, the higher the NNT, the less effective the intervention.7

The advantage of NNT is that it provides clinicians who are taking therapeutic decisions with a more understandable concept of the effectiveness of a treatment.8 Its use is increasing in dermatology, and particularly psoriasis, because very similar efficacy variables are used in the different clinical trials and the populations studied are very homogeneous.7

The objective of this study was to determine the efficiency, in terms of cost per NNT stratified by PASI response levels, of the biologic therapies available in Spain for the treatment of moderate to severe plaque psoriasis.

Methods

Details of the methodology used for the original NMA and the systematic literature review have been published previously.9,10 This NMA provides indirect comparisons for all the biologic treatments currently used in the management of moderate to severe plaque psoriasis in Spain. The literature review included all the studies published in English between January 1990 and November 2015 and all the Phase II, III, and IV randomized clinical trials carried out with each biologic agent. The primary endpoint evaluated in the NMA was the PASI 75, 90, and 100 response (the number of patients with a 75%, 90% or 100% reduction in their baseline PASI score) at the end of the first 12 weeks for most biologic agents, at 10 weeks in the case of infliximab, and at 16 weeks for adalimumab. In this analysis, the NNT to achieve PASI 75, 90 and 100 responses was calculated as the difference in response between the biologic agent and placebo at the end of the interval considered. NNT was calculated as the inverse of the probability of response to biologic treatment minus the probability of response to placebo (Table 1).

Table 1.

NNT per PASI Response Level With Placebo as the Comparator (CrI 2.5-97.5%).

Drug  NNT PASI 75  CrI 2.5%-97.5%  NNT PASI 90  CrI 2.5%-97.5%  NNT PASI 100  CrI 2.5%-97.5% 
Ixekizumab 80mg Q2W  1.18  1.13-1.25  1.41  1.26-1.61  2.46  1.93-3.19 
Secukinumab 300 mg  1.30  1.21-1.41  1.72  1.47-2.04  3.60  2.64-4.87 
Ustekinumab 45 mg  1.51  1.37-1.71  2.27  1.85-2.84  5.82  4.04-8.37 
Ustekinumab 90 mg  1.43  1.30-1.60  2.04  1.68-2.54  4.87  3.40-7.01 
Adalimumab 80/40 mg EOW  1.92  1.60-2.36  3.35  2.43-4.66  10.82  6.42-17.85 
Etanercept 50 mg QIW  2.34  1.42-4.25  4.59  2.02-10.47  18.07  4.70-54.87 
Infliximab 5 mg/kg  1.31  1.20-1.45  1.74  1.44-2.14  3.67  2.53-5.28 

Abbreviations: EOW, every other week; CrI, credible interval; NNT, number needed to treat; PASI, Psoriasis Area and Severity Index; QIW, weekly; Q2W, every 2 weeks.

NNT=1/(probability of response with biologic treatment – probability of response with placebo)

The cost in Spain of the biologic agents studied was based on the manufacturer's price (MP) for each pharmaceutical formulation as reported in the Bot Plus 2.0 database published by the General Council of Official Spanish Pharmacists Associations (CGCOF)11 applying the corresponding discount for each drug in accordance with RDL 8/201012 (Table 2).

Table 2.

Official Manufacturer's Price (MP) for the Biologic Agents, Showing Applicable Discounts, Number of Pens or Vials per Pack, and Dose per Pen or Vial.

Drug  Pens or Vials per Pack  Dose per Pen or Vial, mg  BOT Plus MP, €  MP per Pen or Vial After Discount, €  RDL 8/2010 discount 
Ixekizumab  80  1010.00  934.25  7.5% 
Secukinumab  150  1143.11  528.69  7.5% 
Ustekinumab  45  2747.36  2541.31  7.5% 
Ustekinumab  90  3100.00  2867.50  7.5% 
Adalimumab  40  1028.29  475.58  7.5% 
Etanercepta  50  676.29  169.07  0% 
Infliximaba  100  536.28  536.28  0% 
a

Approved biosimilars already exist for these drugs. The price of these on PVL BOT Plus ranges from €676.29 to €760.84 for etanercept biosimilars and from €439.75 to 482.65 for infliximab biosimilars.

The resulting value was multiplied by the number of doses required for the first year of treatment as per the Summary of Product Characteristics for each drug,13–18 adjusted for the calculations at 52 weeks (Table 3). The cost of infliximab was calculated for an average patient weight of 80kg, since the dosage of this drug is dependent on the patient's weight.19

Table 3.

Dosage, Number of Injections, and Cost per Patient for the First Year of Treatment.

Drug  Dosage  No. of injections per year  Annual Cost, € 
Ixekizumab  160 mg in wk 0, followed by 80mg in wks 2, 4, 6, 8, 10 and 12, and then a maintenance dose of 80 mg every 4 wks  17  15882 
Secukinumab  300 mg in wks 0, 1, 2 and 3 followed by 300mg monthly from wk 4 onwards  30  15861 
Ustekinumab  In patients weighing < 100 kg, 45mg followed by a second dose of 45 mg 4 wks later and then 45 mg every 12 wks thereafter  12707 
  In patients weighing > 100 kg, 90 mg followed by an additional dose of 90 mg 4 wks later and then 90 mg every 12 wks thereafter  14338 
Adalimumab  80 mg, followed by 40 mg every 2 wks  28  13316 
Etanercept  50 mg twice weekly for 12 wks, followed by a maintenance regimen of 50 mg/wk  64  10821 
Infliximaba  5 mg/kg followed by additional doses of 5 mg/kg at wks 2 and 6 and every 8 wks thereafter  17161 

Mean patient weight: 80kg.

The cost per NNT for each agent was obtained by multiplying the cost of the drug in the first year of treatment by the NNT for each of the levels of PASI response considered.

We also performed a sensitivity analysis that took into account only the number of injections during the response assessment period (from 10 to 16 weeks depending on the drug). The number of injections and the cost of treatment during this period, are shown in Table 4.

Table 4.

Data on Actual Response Used in Sensitivity Analysis, With Number of Injections During the Assessment Period and Cost per Patient.

Drug  Time to Response, wks  No. of Injections  Cost, € 
Ixekizumab  12  7474 
Secukinumab  12  14  7402 
Ustekinumab  12  5083 
  12  5735 
Adalimumab  16  10  4756 
Etanercept  12  24  4058 
Infliximaba  10  6435 

Mean patient weight: 80kg.

Results

Table 5 and Figure 1 show the cost per NNT to achieve a PASI 75, 90, or 100 response during the first year of treatment for each of the biologic therapies available in Spain that are used to treat moderate to severe plaque psoriasis.

Table 5.

Cost per NNT in the First Year of Treatment.

DrugCost per NNT, €    Cost per NNT, €    Cost per NNT, €   
PASI 75  CrI 2.5%-97.5%  PASI 90  CrI 2.5%-97.5%  PASI 100  CrI 2.5%-97.5% 
Ixekizumab 80mg Q2W  18741  17947-19853  22394  20012-25570  39070  30653-50664 
Secukinumab 300 mg  20619  19191-22364  27280  23315-32356  57098  41872-77241 
Ustekinumab 45 mg  19187  17408-21728  28844  23507-36087  73952  51334-106354 
Ustekinumab 90 mg  20503  18639-22940  29249  24087-36417  69824  48748-100506 
Adalimumab 80/40 mg EOW  25567  21306-31427  44610  32359-62054  144083  85491-237697 
Etanercept 50 mg QIW  25320  15365-45988  49667  21858-113292  195529  50857-593729 
Infliximab 5 mg/kg  22481  20593-24883  29860  24712-36724  62981  43417-90610 

Abbreviations: EOW, every other week; CrI, credible interval; NNT, number needed to treat; PASI, Psoriasis Area and Severity Index; QIW, weekly; Q2W, every 2 weeks.

Figure 1.

Cost per NNT for the first year of treatment with biologic therapies, stratified by response level (PASI 75, 90 and 100). The error bars represent credible intervals (2.5%−97.5%). Q2W indicates every 2 weeks; Q1W, weekly.

(0.12MB).

The cost per NNT of all the biologic therapies increased with each increment in PASI response (75/90/100), taking into account the first year of treatment.

For the PASI 75 response, the order from lowest to highest cost per NNT was as follows: ixekizumab (€18741) <ustekinumab 45mg (€19187) <ustekinumab 90mg (€20503) <secukinumab (€20619) <infliximab (€22481) <etanercept (€25320) <adalimumab (€25567).

For the PASI 90 response, the order from lowest to highest cost per NNT was as follows: ixekizumab (€22394) <secukinumab (€ 27280) <ustekinumab 45mg (€ 28844) <ustekinumab 90mg (€ 29249) <infliximab (€29860)) <adalimumab (€ 44610) <etanercept (€49667).

For the PASI 100 response, the order from lowest to highest cost per NNT was as follows: ixekizumab (€39070) <secukinumab (€57098) <infliximab (€62981) <ustekinumab 90mg (€69824) <ustekinumab 45mg (€73952) <adalimumab (€144083) <etanercept (€195529).

The sensitivity analysis shows the cost per NNT for each drug for the period during which the PASI was actually measured: week 10, 12, or 16 depending on the drug (Table 6, Fig. 2).

Table 6.

Cost per NNT During the Treatment Response Assessment Period.

DrugCost per NNT, €    Cost per NNT, €    Cost per NNT, €   
PASI 75  CrI 2.5%-97.5%  PASI 90  CrI 2.5%-97.5%  PASI 100  CrI 2.5%-97.5% 
Ixekizumab 80mg Q2W  8819  8446-9343  10538  9417-12033  18386  14425-23842 
Secukinumab 300 mg  9178  8660-9918  11621  10140-13696  22575  16950-30347 
Ustekinumab 45 mg  6607  6150-7166  8742  7471-10369  18297  13418-24752 
Ustekinumab 90 mg  8660  7857-9807  13018  10610-16287  33378  23169-48002 
Adalimumab 80/40 mg EOW  6801  6183-7609  9702  7990-12080  23161  16170-33338 
Etanercept 50 mg QIW  7791  6492-9576  13593  9860-18909  43905  26051-72431 
Infliximab 5 mg/kg  8430  7722-9331  11198  9267-13772  23618  16281-33979 

Abbreviations: EOW, Every other week; CrI, credible interval; QIW, weekly; Q2W, every 2 weeks.

Figure 2.

Cost per NNT for the period in which response was actually measured (from 10 to 16 weeks depending on the drug), stratified by response level (PASI 75, 90 and 100). The error bars represent credible intervals (2.5% -97, 5%).

(0.13MB).

For the PASI 75 response, the order from lowest to highest cost per NNT was as follows: ustekinumab 45mg (€6607) <adalimumab (€6801) <etanercept (€7791) <infliximab (€8430) <ustekinumab 90mg (€8663) <ixekizumab (€8819) <secukinumab (€9178).

For the PASI 90 response, the order from lowest to highest cost per NNT was as follows: ustekinumab 45mg (€8742) <adalimumab (€9702) <ixekizumab (€10538) <infliximab (€11198) <secukinumab (€11 621) <ustekinumab 90mg (€13018) <etanercept (€13593)).

For the PASI 100 response, the order from lowest to highest cost per NNT was as follows: ustekinumab 45mg (€18297) <ixekizumab (€18396) <secukinumab (€22575) <adalimumab (€23161) <infliximab (€23618) <ustekinumab 90mg (€33378) <etanercept (€43905).

Discussion

In recent years, the advent of biologic therapies has led to improved clinical outcomes in patients with moderate to severe plaque psoriasis. However, the increasing expenditure on these drugs makes it necessary to analyze the efficiency of the available treatments. Our findings show that the more effective drugs are also the most efficient. The order from lowest to highest cost per NNT of the biologic agents studied evidences the greater efficiency of the therapies with more recent mechanisms of action, such as the IL-17 and IL-12/23 inhibitors, which obtained higher response levels than TNF-α inhibitors in clinical trials. Moreover, the cost per NNT increases when the treatment objective requires more complete skin clearance (a higher PASI response level). However, given the overlapping credible intervals for most of the biologic agents and PASI response levels studied, these sequences are only indicative and the differences observed are not statistically significant.

This is the first study to compare the cost per NNT of all the biologic treatments currently available in Spain for the treatment of moderate to severe plaque psoriasis. The more recently developed biologic agents (certolizumab pegol, brodalumab, guselkumab, and tildrakizumab) were not included in this study for 2 reasons: first, because the results of clinical trials were not available when the NMA was performed; and, second, because the official price had not been established. However NNT values for these drugs have since been published.20–22 Our findings are consistent with those of earlier studies, which reported very similar NNT values for biologic therapies, likewise obtained through indirect comparison methods, such as NMA,22,23 and similar sequences from lowest to highest cost per NNT.10,19,24–26

While a PASI 75 response has traditionally been considered the treatment objective of reference in this setting,27,28 patients who achieve a PASI 90 response or higher have a score of 0 to 1 on the Dermatology Quality of Life Index (DLQI) in a significantly higher percentage than those whose response is PASI 75. This score of 0 to 1 on the DLQI scale signifies that the disease has a zero or minimal impact on the patient's quality of life.29–31 This improvement in patient quality of life arising from an improved response to treatment, together with the availability of new therapies that can achieve a PASI 90 response in a sizable percentage of patients, has led to a PASI 90 or higher response being considered the most important treatment objective.32–34 It is interesting to note that, for most of the biologic therapies, the cost increase per NNT required to achieve a PASI 90 as compared to a PASI 75 response is less than the cost increase per NNT to achieve a PASI 100 compared to a PASI 90 response. This is a consequence of the skin clearance results achieved by the biologic agents during clinical development: the newer biologics achieved PASI 90 responses in a higher proportion of patients and also achieved higher PASI 100 response rates than those achieved by earlier biologic treatments, such as the TNF-α inhibitors. These differences are reflected in the cost per NNT results reported in this study.

Analysis of cost per NNT differs from complete economic evaluations, such as cost-effectiveness analysis.35 That methodology, endorsed by scientific societies and commonly used to assess health technologies, models outcome and cost variables over a considerable period, taking into account not only the pharmacological cost of therapies but also the consumption of other types of resources involved in the management of the disease, an important consideration when making decisions on how to allocate the health care budget. However, calculating the cost per unit of clinical efficacy (NNT) may be another approach that can provide very comprehensible information for clinicians and others involved in making health care decisions. Cost per NNT is not, however, a useful measure for establishing a threshold to inform decisions on how much should reasonably be invested in achieving a health outcome, unlike cost-effectiveness analysis, which does provide information that can inform such decisions. It may, therefore, be useful to have both methods in order to provide information to inform different types of decisions.

One of the limitations of this study is the lack of data from clinical trials that directly compare the different drugs. This lack of data led us to combine the evidence available and to carry out indirect comparisons by means of an NMA of all the studies on the biologic therapies available in Spain published in the current literature.9,10 Our NMA was based on a systematic literature review of clinical trials published before the end of November 2015 and, given the high level of activity in this area, other studies using a similar methodology (NMA) and including clinical trials after that date have been carried out. However, the findings reported by the later NMA corroborate the results of our study.20,26 The NNT obtained in our NMA were used to calculate the cost of the first year of treatment. In the methodology used, it was assumed that all the drugs studied maintained the efficacy observed in the short term (during the induction period) through to the end of the first year of treatment. This approach provides the best possible approximation of the actual situation as we found no clinical trials with homogeneous designs providing data on the maintenance of response over a longer period to facilitate indirect comparisons (and the calculation of cost per NNT). Basing the analysis on the assumption that the response was maintained over a longer period than the induction phase is not a new approach: the same assumption has been made by the authors of most studies that compare the cost of biologic therapies over longer periods.19,24,25 We also performed a sensitivity analysis including only the data from the period during which the PASI response was assessed in the clinical trials included in the NMA. In that analysis, ustekinumab was the most efficient treatment for all levels of PASI response, both because of the clinical response obtained and the dosage regimen used. The cost per NNT of the new IL-17 inhibitors decreases with each increment in PASI response (75/90/100). Another limitation of this study is the use of the manufacturer's catalogue price (MP) to calculate the cost of treatment. In the current Spanish system, the official MP may be discounted by the vendor to ensure that the treatment is covered by the National Health System (giving rise to a subsidized price). This reduced price more closely reflects the actual cost of the drug. It is, however, extremely difficult to obtain precise data on the actual prices paid. Moreover, the final price of biologic agents in Spain is also subject to additional discounts in hospitals, giving rise to even greater variability. For all these reasons, we opted to base our analysis on the MP. This study provides information on the efficiency, in terms of cost per NNT, of the biologic treatments currently available in Spain for the treatment of moderate to severe plaque psoriasis, stratified by level of treatment response (PASI 75, 90 and 100). The results show that the more effective biologic treatments are also more efficient. Of the therapies studied, ixekizumab was the biologic agent with the lowest cost per NNT and, therefore, the most efficient treatment for moderate to severe plaque psoriasis at all PASI response levels over a 1-year treatment period. Ustekinumab was the most efficient treatment when only the response assessment period was taken into account (10 to 16 weeks depending on the drug).

Funding

This study was funded by Eli Lilly and Company.

Conflicts of Interest

P. de la Cueva has participated in clinical trials or received consultancy or lecture fees from Abbvie, Almirall, Biogen, Boehringer-Ingelhaim, Celgene, Gebro, Janssen, Leo Pharma, MSD, Novartis, Pfizer, Lilly, Sanofi, and UDC Pharma.

M. Nuñez, T. Huete, JA Sacristán, S. Hartz and T. Dilla are employees of Eli Lilly and Company.

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Please cite this article as: Núñez M, Huete T, de la Cueva P, Sacristán JA, Hartz S, Dilla T. Evaluación de la eficiencia de los tratamientos biológicos en la psoriasis moderada a grave en España: análisis de coste por número necesario a tratar (NNT). Actas Dermosifiliogr. 2019;110:546–553.

Copyright © 2018. Elsevier España, S.L.U. and AEDV
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