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and 33&#46;1&#37; of patients with plaque psoriasis&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4</span></a> Subanalysis of the ESTEEM 1 and ESTEEM 2 trials&#44; focusing on those patients who presented with palmoplantar hyperkeratotic lesions in addition to plaques&#44; showed that 48&#37; of patients with a PGA greater than or equal to 3 achieved physician general assessment &#40;PGA&#41; 0&#47;1 after the first 16 weeks of treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> In another subanalysis of the ESTEEM clinical trials on the effectiveness of treatment in scalp psoriasis&#44; 40&#37; to 50&#37; of patients achieved PGA 0&#47;1 at 16 weeks of treatment&#44; with maintenance of response and even improvement at week 52&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> These results&#44; although derived from a subanalysis&#44; suggest that apremilast is an effective drug for treatment of hard-to-treat areas&#46; However&#44; data from clinical practice to support this suggestion are limited&#46; The objective of the present study was to assess the data obtained for persistence and safety in our clinical practice&#44; after 2<span class="elsevierStyleHsp" style=""></span>years of apremilast use in different clinical forms of psoriasis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Material and Methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">A retrospective observational study was conducted in the Hospital Universitario y Polit&#233;cnico La Fe in Valencia&#44; Spain&#46; All patients with psoriasis&#44; except for those with pustular forms&#44; were included if they had received at least 1 dose of apremilast between January 2016 and December 2017&#46; Dosing was as per the prescribing information&#46; Given the clinical practice setting&#44; use of topical treatment was permitted&#44; and apremilast could be initiated without the need for a prior washout period&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The persistence with and safety of treatment&#44; as well as the influence on these outcomes of demographic variables &#40;sex&#44; age&#44; weight&#44; height&#44; body mass index &#91;BMI&#93;&#41; and clinical variables &#40;duration of psoriasis&#44; number of prior treatments&#44; and initial PASI and PGA&#41; were analyzed&#46; A patient was considered as belonging to the subgroup with plaques predominantly on the scalp when more than 20&#37; of body area was affected and less than 3&#37; of the lesions affected the trunk and&#47;or limbs&#46; The primary reason for failure was defined as the absence of PASI 50 improvement in plaque psoriasis&#44; or the absence of a decrease of at least 2 points in PGA in palmoplantar &#40;PP&#41; and scalp presentations&#46; The secondary reason for failure was defined as an adequate initial response lost over at least 2 consecutive visits&#46; For all patients&#44; the presence&#44; seriousness&#44; and duration of adverse effects was evaluated&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Descriptive analysis of the variables was performed with absolute and relative frequencies and means and SDs&#46; Inferential analysis of the qualitative variables was performed using chi-squared based tests&#46; Survival analysis was performed using the Kaplan-Meier method and log-rank test&#44; along with the 50th and 75th percentile for calculation of time of probability of survival&#44; with a study event defined as withdrawal of treatment for any reason&#46; The statistical analyses were performed using the SPSS statistical package&#44; with the limit of significance set to <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">All medical histories of the patients were treated anonymously and in accordance with privacy and data protection laws&#46; The study was classified by the Spanish Agency for Evaluation of Medicinal Products as a postauthorization study and was approved by the ethics committee of the Hospital Universitario y Polit&#233;cnico La Fe&#44; Valencia&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">The study included 30 patients&#44; 18 women and 12 men&#44; with a mean age of 44 years &#40;range&#44; 22&#8211;71 years&#41; and a mean BMI of 28&#46;3<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> &#40;19&#8211;38<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#46; The median duration of follow-up was 9 months &#40;range&#44; 0&#46;5&#8211;18 months&#41;&#46; Ten patients presented plaque psoriasis&#44; 8 predominantly on the scalp and 12 had PP forms&#46; In 19 patients &#40;63&#37;&#41;&#44; the indication for apremilast was based solely on the clinical criterion of hard-to-treat area&#46; The remaining indications were as follows&#58; lack of control with traditional drugs or their contraindication &#40;4&#47;30&#59; 13&#37;&#41;&#44; untreated latent tuberculosis infection &#40;2&#47;30&#59; 7&#37;&#41;&#44; active hepatitis B &#40;2&#47;30&#44; 7&#37;&#41;&#44; Lynch syndrome &#40;1&#47;30&#44; 3&#37;&#41;&#44; history of spontaneous bacterial peritonitis &#40;1&#47;30&#44; 3&#37;&#41;&#44; and autoimmune hepatitis &#40;1&#47;30&#44; 3&#37;&#41;&#46; In 7 patients &#40;23&#37;&#41;&#44; apremilast was the drug used as the first systemic treatment&#46; Of the 23 patients &#40;77&#37;&#41; who had received some type of prior systemic treatment&#44; 19 patients had received traditional agents &#40;63&#37;&#41;&#44; 3 had received traditional drugs and biologics &#40;10&#37;&#41;&#44; and 1 patient only biological agents &#40;3&#37;&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">At the end of the study&#44; only 15 patients remained on treatment&#46; The time to 50&#37; survival and 75&#37; survival probability was 18&#46;5 and 4 months&#44; respectively&#44; for all patients&#44; regardless of indication&#46; No patient with plaque psoriasis predominantly on the scalp completed the study period on treatment&#44; with a 50&#37; and 75&#37; survival probability of 5 and 2&#46;5 months&#44; respectively&#46; In plaque psoriasis&#44; the 75&#37; survival probability was 4 months while in the PP form it was 15&#46;6 months&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows reasons for withdrawal&#46; Overall&#44; the median time to withdrawal of the drug was 2 months &#40;range&#44; 0&#46;5&#8211;4 months&#41; for adverse reactions&#44; 5&#46;5 months &#40;range&#44; 4&#8211;8 months&#41; for primary failure&#44; and 14&#46;5 months &#40;range&#44; 11&#8211;18 months&#41; for secondary failure&#46; In the 3 types of psoriasis included&#44; we did not identify a statistically significant association between a decrease in PGA<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2 points and BMI&#44; sex&#44; age&#44; and intake of prior treatments&#46; In our study&#44; only the scalp clinical form was significantly associated with withdrawal due to primary and&#47;or secondary failure&#44; as well as lack of decrease of at least 2 points on the PGA &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;003&#41;&#46; Analysis using Kaplan-Meier curves showed a significant reduction in treatment survival in patients with scalp psoriasis &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Twenty-two out of 30 patients &#40;73&#37;&#41; experienced adverse effects related to drug administration&#59; of these&#44; 60&#37; &#40;13&#47;22&#41; had 2 or more adverse effects&#46; In total&#44; 41 adverse effects were reported &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; No patient experienced severe effects or infectious events&#46; In the 15 patients who completed the study&#44; the median duration of side effects was 3&#46;4 months &#40;range&#44; 1&#8211;10<span class="elsevierStyleHsp" style=""></span>months&#41;&#44; with resolution during the first month of treatment in 6&#47;15 cases &#40;40&#37;&#41;&#44; and in the first 2 months in 8&#47;15 &#40;53&#37;&#41;&#46; We did not find any statistically significant association between adverse effects and age&#44; BMI&#44; clinical form&#44; response to treatment&#44; or sex&#46; However&#44; of note is a trend &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;077&#41; between patients with normal weight and the onset of adverse effects&#44; such that 100&#37; of patients with normal weight had adverse effects compared with only 50&#37; of patients with obesity&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">Efficacy&#44; persistence&#44; and safety of drugs in clinical practice can be different to what is reported in clinical trials&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7&#44;8</span></a> Therefore&#44; real world studies in a clinical practice setting are necessary&#46; Our results with apremilast in plaque psoriasis were similar to those published recently by Vujic et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> who studied 48 patients in clinical practice for 2 years&#46; The authors did not find any statistically significant differences between drug survival and sex&#44; age&#44; smoking habit&#44; and presence of joint involvement&#44; initial PASI&#44; or prior treatments&#46; They did however find a trend towards an association between the probability of achieving a PASI 75 response or better and BMI less than 30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#46; In our series&#44; we only identified a trend for greater risk of adverse effects in patients with normal weight&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> In reference to the adverse effects&#44; our results are similar to those obtained both in clinical trials and other studies in clinical practice settings&#44; with diarrhea&#44; abdominal pain&#44; and headache being the most frequent&#44; occurring in 60&#37; to 80&#37; of patients&#46; It would therefore be advisable to avoid the drug or monitor closely those patients with underlying digestive problems&#44; headaches&#44; or migraines&#46; In our series&#44; we did not report any serious or potentially serious adverse effects&#44; even in patients with underlying infectious disease or neoplasms&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">This study is subject to a series of limitations&#46; First&#44; this was a retrospective study&#44; with no control group and a small number of patients&#44; particularly in view of the subsequent subdivision by clinical type&#46; In addition&#44; the concomitant use of topical corticosteroids was not appropriately quantified&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion&#44; in our experience&#44; apremilast is an effective and safe drug in plaque psoriasis and PP psoriasis&#46; In our series&#44; the clinical forms with predominantly scalp involvement did not respond well to treatment&#46; Adverse effects were reported in nearly two-thirds of the patients&#44; mainly in the form of gastrointestinal conditions or headache&#44; and although most of these were mild or moderate in intensity&#44; they may compromise persistence with treatment&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conflicts of Interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">A&#46; Sahuquillo-Torralba and R&#46; Botella Estrada have worked as consultants and&#47;or received honoraria as speakers and&#47;or participated in clinical trials sponsored by companies that develop drugs used in the treatment of psoriasis&#44; including AbbVie&#44; Celgene&#44; Janssen-Cilag&#44; LEO Pharma&#44; Lilly&#44; Novartis&#44; and Pfizer&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">E&#46; Monte Boquet has worked as a consultant and&#47;or received honoraria as a speaker for companies that develop drugs used in the treatment of psoriasis&#44; including AbbVie&#44; Celgene&#44; Janssen-Cilag&#44; LEO Pharma&#44; Lilly&#44; Novartis&#44; and Pfizer&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The remaining authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Apremilast is a phosphodiesterase-4 inhibitor taken orally&#46; Little information about its use in routine clinical practice is available&#46; We aimed to assess treatment safety and persistence rates in patients on apremilast for different forms of plaque psoriasis&#46; This observational retrospective study included 30 patients with psoriasis who were treated with apremilast between January 2016 and December 2017 in our hospital&#46; Twelve patients had palmar-plantar psoriasis&#44; 8 had plaque psoriasis mainly on the scalp&#44; and 10 had plaque psoriasis in other locations&#46; The probable period of treatment persistence in patients in the 50th percentile was 18&#46;5 months according to survival analysis of the series overall&#46; Our experience suggests that apremilast is effective and safe for treating palmar-plantar psoriasis and plaques at other locations but not for treating scalp psoriasis&#46; Adverse effects that compromise treatment occur in nearly two-thirds of the patients&#46;</p></span>"
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        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">El apremilast es un inhibidor v&#237;a oral de la fosfodiesterasa-4 con pocos datos de pr&#225;ctica cl&#237;nica habitual&#46; Nuestro objetivo fue evaluar la persistencia y la seguridad del apremilast en la pr&#225;ctica cl&#237;nica en distintas formas cl&#237;nicas de psoriasis&#46; Se realiz&#243; un estudio observacional retrospectivo de los 30 pacientes con psoriasis que recibieron el f&#225;rmaco entre enero de 2016 y diciembre de 2017 en nuestro centro&#44; 10 con psoriasis en placas&#44; 8 con placas predominantemente en el cuero cabelludo y 12 palmo-plantares&#46; El tiempo global de probabilidad de supervivencia del 50&#37; fue de 18&#44;5<span class="elsevierStyleHsp" style=""></span>meses&#46; En nuestra experiencia&#44; el apremilast es un f&#225;rmaco efectivo y seguro para la psoriasis en placas y palmo-plantar&#44; no as&#237; para la afectaci&#243;n del cuero cabelludo&#46; Los efectos secundarios ocurren en casi dos tercios de los pacientes comprometiendo la persistencia del tratamiento&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Sahuquillo-Torralba A&#44; de Unamuno Bustos B&#44; Rodr&#237;guez Serna M&#44; Monte Boquet E&#44; Botella Estrada R&#46; Persistencia y seguridad del apremilast en el tratamiento de la psoriasis en la pr&#225;ctica cl&#237;nica habitual&#58; experiencia en 30 pacientes&#46; Actas Dermosifiliogr&#46; 2020&#59;111&#58;415&#8211;418&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier survival analysis&#46; Abbreviations&#58; Plaque&#44; plaque psoriasis&#59; PP&#44; palmoplantar psoriasis&#59; SC&#44; scalp psoriasis&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Headache&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11 &#40;37&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5 &#40;42&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;40&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;27&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;10&#37;&#41;&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">3 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Asthenia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6 &#40;20&#37;&#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
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                  \t\t\t\t">4 &#40;40&#37;&#41;&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">2 &#40;17&#37;&#41;&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">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;10&#37;&#41;&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">0&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">1 &#40;8&#37;&#41;&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">2 &#40;25&#37;&#41;&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"><span class="elsevierStyleHsp" style=""></span>Myalgia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;7&#37;&#41;&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">2 &#40;20&#37;&#41;&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">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;3&#37;&#41;&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">0&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 &#40;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                        "tituloSerie" => "Br J Pharmacol"
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                      "titulo" => "The pharmacodynamic impact of apremilast&#44; an oral phosphodiesterase 4 inhibitor&#44; on circulating levels of inflammatory biomarkers in patients with psoriatic arthritis&#58; substudy results from a phase III&#44; randomized&#44; placebo-controlled trial &#40;PALACE 1&#41;"
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                      "titulo" => "Apremilast&#44; an oral phosphodiesterase 4 &#40;PDE4&#41; inhibitor&#44; in patients with moderate to severe plaque psoriasis&#58; results of a phase III&#44; randomized&#44; controlled trial &#40;Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis &#91;ESTEEM&#93; 1&#41;"
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                      "titulo" => "Apremilast&#44; an oral phosphodiesterase 4 inhibitor&#44; in patients with difficult-to-treat nail and scalp psoriasis&#58; results of 2 phase III randomized&#44; controlled trials &#40;ESTEEM 1 and ESTEEM 2&#41;"
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                          "autores" => array:6 [
                            0 => "K&#46; Martin"
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                        "numero" => "Suppl&#46; 15"
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Brief Communication
Treatment Persistence and Safety of Apremilast in Psoriasis: Experience With 30 Patients in Routine Clinical Practice
Persistencia y seguridad del apremilast en el tratamiento de la psoriasis en la práctica clínica habitual: experiencia en 30 pacientes
A. Sahuquillo-Torralbaa,
Autor para correspondencia
saucodos@gmail.com

Corresponding author.
, B. de Unamuno Bustosa, M. Rodríguez Sernaa, E. Monte Boquetb, R. Botella Estradaa,c
a Servicio de Dermatología, Hospital Universitari i Politècnic La Fe, Valencia, Spain
b Servicio de Farmacia Hospitalaria, Hospital Universitari i Politècnic La Fe, Valencia, Spain
c Facultad de Medicina, Universidad de Valencia, Valencia, Spain
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and 33&#46;1&#37; of patients with plaque psoriasis&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4</span></a> Subanalysis of the ESTEEM 1 and ESTEEM 2 trials&#44; focusing on those patients who presented with palmoplantar hyperkeratotic lesions in addition to plaques&#44; showed that 48&#37; of patients with a PGA greater than or equal to 3 achieved physician general assessment &#40;PGA&#41; 0&#47;1 after the first 16 weeks of treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> In another subanalysis of the ESTEEM clinical trials on the effectiveness of treatment in scalp psoriasis&#44; 40&#37; to 50&#37; of patients achieved PGA 0&#47;1 at 16 weeks of treatment&#44; with maintenance of response and even improvement at week 52&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> These results&#44; although derived from a subanalysis&#44; suggest that apremilast is an effective drug for treatment of hard-to-treat areas&#46; However&#44; data from clinical practice to support this suggestion are limited&#46; The objective of the present study was to assess the data obtained for persistence and safety in our clinical practice&#44; after 2<span class="elsevierStyleHsp" style=""></span>years of apremilast use in different clinical forms of psoriasis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Material and Methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">A retrospective observational study was conducted in the Hospital Universitario y Polit&#233;cnico La Fe in Valencia&#44; Spain&#46; All patients with psoriasis&#44; except for those with pustular forms&#44; were included if they had received at least 1 dose of apremilast between January 2016 and December 2017&#46; Dosing was as per the prescribing information&#46; Given the clinical practice setting&#44; use of topical treatment was permitted&#44; and apremilast could be initiated without the need for a prior washout period&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The persistence with and safety of treatment&#44; as well as the influence on these outcomes of demographic variables &#40;sex&#44; age&#44; weight&#44; height&#44; body mass index &#91;BMI&#93;&#41; and clinical variables &#40;duration of psoriasis&#44; number of prior treatments&#44; and initial PASI and PGA&#41; were analyzed&#46; A patient was considered as belonging to the subgroup with plaques predominantly on the scalp when more than 20&#37; of body area was affected and less than 3&#37; of the lesions affected the trunk and&#47;or limbs&#46; The primary reason for failure was defined as the absence of PASI 50 improvement in plaque psoriasis&#44; or the absence of a decrease of at least 2 points in PGA in palmoplantar &#40;PP&#41; and scalp presentations&#46; The secondary reason for failure was defined as an adequate initial response lost over at least 2 consecutive visits&#46; For all patients&#44; the presence&#44; seriousness&#44; and duration of adverse effects was evaluated&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Descriptive analysis of the variables was performed with absolute and relative frequencies and means and SDs&#46; Inferential analysis of the qualitative variables was performed using chi-squared based tests&#46; Survival analysis was performed using the Kaplan-Meier method and log-rank test&#44; along with the 50th and 75th percentile for calculation of time of probability of survival&#44; with a study event defined as withdrawal of treatment for any reason&#46; The statistical analyses were performed using the SPSS statistical package&#44; with the limit of significance set to <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">All medical histories of the patients were treated anonymously and in accordance with privacy and data protection laws&#46; The study was classified by the Spanish Agency for Evaluation of Medicinal Products as a postauthorization study and was approved by the ethics committee of the Hospital Universitario y Polit&#233;cnico La Fe&#44; Valencia&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">The study included 30 patients&#44; 18 women and 12 men&#44; with a mean age of 44 years &#40;range&#44; 22&#8211;71 years&#41; and a mean BMI of 28&#46;3<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> &#40;19&#8211;38<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#46; The median duration of follow-up was 9 months &#40;range&#44; 0&#46;5&#8211;18 months&#41;&#46; Ten patients presented plaque psoriasis&#44; 8 predominantly on the scalp and 12 had PP forms&#46; In 19 patients &#40;63&#37;&#41;&#44; the indication for apremilast was based solely on the clinical criterion of hard-to-treat area&#46; The remaining indications were as follows&#58; lack of control with traditional drugs or their contraindication &#40;4&#47;30&#59; 13&#37;&#41;&#44; untreated latent tuberculosis infection &#40;2&#47;30&#59; 7&#37;&#41;&#44; active hepatitis B &#40;2&#47;30&#44; 7&#37;&#41;&#44; Lynch syndrome &#40;1&#47;30&#44; 3&#37;&#41;&#44; history of spontaneous bacterial peritonitis &#40;1&#47;30&#44; 3&#37;&#41;&#44; and autoimmune hepatitis &#40;1&#47;30&#44; 3&#37;&#41;&#46; In 7 patients &#40;23&#37;&#41;&#44; apremilast was the drug used as the first systemic treatment&#46; Of the 23 patients &#40;77&#37;&#41; who had received some type of prior systemic treatment&#44; 19 patients had received traditional agents &#40;63&#37;&#41;&#44; 3 had received traditional drugs and biologics &#40;10&#37;&#41;&#44; and 1 patient only biological agents &#40;3&#37;&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">At the end of the study&#44; only 15 patients remained on treatment&#46; The time to 50&#37; survival and 75&#37; survival probability was 18&#46;5 and 4 months&#44; respectively&#44; for all patients&#44; regardless of indication&#46; No patient with plaque psoriasis predominantly on the scalp completed the study period on treatment&#44; with a 50&#37; and 75&#37; survival probability of 5 and 2&#46;5 months&#44; respectively&#46; In plaque psoriasis&#44; the 75&#37; survival probability was 4 months while in the PP form it was 15&#46;6 months&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows reasons for withdrawal&#46; Overall&#44; the median time to withdrawal of the drug was 2 months &#40;range&#44; 0&#46;5&#8211;4 months&#41; for adverse reactions&#44; 5&#46;5 months &#40;range&#44; 4&#8211;8 months&#41; for primary failure&#44; and 14&#46;5 months &#40;range&#44; 11&#8211;18 months&#41; for secondary failure&#46; In the 3 types of psoriasis included&#44; we did not identify a statistically significant association between a decrease in PGA<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2 points and BMI&#44; sex&#44; age&#44; and intake of prior treatments&#46; In our study&#44; only the scalp clinical form was significantly associated with withdrawal due to primary and&#47;or secondary failure&#44; as well as lack of decrease of at least 2 points on the PGA &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;003&#41;&#46; Analysis using Kaplan-Meier curves showed a significant reduction in treatment survival in patients with scalp psoriasis &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Twenty-two out of 30 patients &#40;73&#37;&#41; experienced adverse effects related to drug administration&#59; of these&#44; 60&#37; &#40;13&#47;22&#41; had 2 or more adverse effects&#46; In total&#44; 41 adverse effects were reported &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; No patient experienced severe effects or infectious events&#46; In the 15 patients who completed the study&#44; the median duration of side effects was 3&#46;4 months &#40;range&#44; 1&#8211;10<span class="elsevierStyleHsp" style=""></span>months&#41;&#44; with resolution during the first month of treatment in 6&#47;15 cases &#40;40&#37;&#41;&#44; and in the first 2 months in 8&#47;15 &#40;53&#37;&#41;&#46; We did not find any statistically significant association between adverse effects and age&#44; BMI&#44; clinical form&#44; response to treatment&#44; or sex&#46; However&#44; of note is a trend &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;077&#41; between patients with normal weight and the onset of adverse effects&#44; such that 100&#37; of patients with normal weight had adverse effects compared with only 50&#37; of patients with obesity&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">Efficacy&#44; persistence&#44; and safety of drugs in clinical practice can be different to what is reported in clinical trials&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7&#44;8</span></a> Therefore&#44; real world studies in a clinical practice setting are necessary&#46; Our results with apremilast in plaque psoriasis were similar to those published recently by Vujic et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> who studied 48 patients in clinical practice for 2 years&#46; The authors did not find any statistically significant differences between drug survival and sex&#44; age&#44; smoking habit&#44; and presence of joint involvement&#44; initial PASI&#44; or prior treatments&#46; They did however find a trend towards an association between the probability of achieving a PASI 75 response or better and BMI less than 30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#46; In our series&#44; we only identified a trend for greater risk of adverse effects in patients with normal weight&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> In reference to the adverse effects&#44; our results are similar to those obtained both in clinical trials and other studies in clinical practice settings&#44; with diarrhea&#44; abdominal pain&#44; and headache being the most frequent&#44; occurring in 60&#37; to 80&#37; of patients&#46; It would therefore be advisable to avoid the drug or monitor closely those patients with underlying digestive problems&#44; headaches&#44; or migraines&#46; In our series&#44; we did not report any serious or potentially serious adverse effects&#44; even in patients with underlying infectious disease or neoplasms&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">This study is subject to a series of limitations&#46; First&#44; this was a retrospective study&#44; with no control group and a small number of patients&#44; particularly in view of the subsequent subdivision by clinical type&#46; In addition&#44; the concomitant use of topical corticosteroids was not appropriately quantified&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion&#44; in our experience&#44; apremilast is an effective and safe drug in plaque psoriasis and PP psoriasis&#46; In our series&#44; the clinical forms with predominantly scalp involvement did not respond well to treatment&#46; Adverse effects were reported in nearly two-thirds of the patients&#44; mainly in the form of gastrointestinal conditions or headache&#44; and although most of these were mild or moderate in intensity&#44; they may compromise persistence with treatment&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conflicts of Interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">A&#46; Sahuquillo-Torralba and R&#46; Botella Estrada have worked as consultants and&#47;or received honoraria as speakers and&#47;or participated in clinical trials sponsored by companies that develop drugs used in the treatment of psoriasis&#44; including AbbVie&#44; Celgene&#44; Janssen-Cilag&#44; LEO Pharma&#44; Lilly&#44; Novartis&#44; and Pfizer&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">E&#46; Monte Boquet has worked as a consultant and&#47;or received honoraria as a speaker for companies that develop drugs used in the treatment of psoriasis&#44; including AbbVie&#44; Celgene&#44; Janssen-Cilag&#44; LEO Pharma&#44; Lilly&#44; Novartis&#44; and Pfizer&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The remaining authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Apremilast is a phosphodiesterase-4 inhibitor taken orally&#46; Little information about its use in routine clinical practice is available&#46; We aimed to assess treatment safety and persistence rates in patients on apremilast for different forms of plaque psoriasis&#46; This observational retrospective study included 30 patients with psoriasis who were treated with apremilast between January 2016 and December 2017 in our hospital&#46; Twelve patients had palmar-plantar psoriasis&#44; 8 had plaque psoriasis mainly on the scalp&#44; and 10 had plaque psoriasis in other locations&#46; The probable period of treatment persistence in patients in the 50th percentile was 18&#46;5 months according to survival analysis of the series overall&#46; Our experience suggests that apremilast is effective and safe for treating palmar-plantar psoriasis and plaques at other locations but not for treating scalp psoriasis&#46; Adverse effects that compromise treatment occur in nearly two-thirds of the patients&#46;</p></span>"
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        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">El apremilast es un inhibidor v&#237;a oral de la fosfodiesterasa-4 con pocos datos de pr&#225;ctica cl&#237;nica habitual&#46; Nuestro objetivo fue evaluar la persistencia y la seguridad del apremilast en la pr&#225;ctica cl&#237;nica en distintas formas cl&#237;nicas de psoriasis&#46; Se realiz&#243; un estudio observacional retrospectivo de los 30 pacientes con psoriasis que recibieron el f&#225;rmaco entre enero de 2016 y diciembre de 2017 en nuestro centro&#44; 10 con psoriasis en placas&#44; 8 con placas predominantemente en el cuero cabelludo y 12 palmo-plantares&#46; El tiempo global de probabilidad de supervivencia del 50&#37; fue de 18&#44;5<span class="elsevierStyleHsp" style=""></span>meses&#46; En nuestra experiencia&#44; el apremilast es un f&#225;rmaco efectivo y seguro para la psoriasis en placas y palmo-plantar&#44; no as&#237; para la afectaci&#243;n del cuero cabelludo&#46; Los efectos secundarios ocurren en casi dos tercios de los pacientes comprometiendo la persistencia del tratamiento&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Sahuquillo-Torralba A&#44; de Unamuno Bustos B&#44; Rodr&#237;guez Serna M&#44; Monte Boquet E&#44; Botella Estrada R&#46; Persistencia y seguridad del apremilast en el tratamiento de la psoriasis en la pr&#225;ctica cl&#237;nica habitual&#58; experiencia en 30 pacientes&#46; Actas Dermosifiliogr&#46; 2020&#59;111&#58;415&#8211;418&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier survival analysis&#46; Abbreviations&#58; Plaque&#44; plaque psoriasis&#59; PP&#44; palmoplantar psoriasis&#59; SC&#44; scalp psoriasis&#46;</p>"
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">All Indications&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Plaque Psoriasis&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Palmoplantar Psoriasis&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Scalp Psoriasis&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Secondary failure&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;16&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Adverse effects&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7 &#40;23&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;30&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;8&#37;&#41;&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">3 &#40;38&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11 &#40;37&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;40&#37;&#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
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                  \t\t\t\t">5 &#40;42&#37;&#41;&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">2 &#40;25&#37;&#41;&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
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                  \t\t\t\t">10 &#40;33&#37;&#41;&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">4 &#40;40&#37;&#41;&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">4 &#40;33&#37;&#41;&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">2 &#40;25&#37;&#41;&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  " align="left" valign="\n
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                  \t\t\t\t">8 &#40;27&#37;&#41;&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">1 &#40;10&#37;&#41;&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">3 &#40;25&#37;&#41;&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">4 &#40;50&#37;&#41;&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"><span class="elsevierStyleHsp" style=""></span>Asthenia&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">6 &#40;20&#37;&#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
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                  \t\t\t\t">4 &#40;40&#37;&#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
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                  \t\t\t\t">2 &#40;17&#37;&#41;&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">0&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"><span class="elsevierStyleHsp" style=""></span>Abdominal pain&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">3 &#40;10&#37;&#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
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                  \t\t\t\t">0&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 &#40;8&#37;&#41;&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">2 &#40;25&#37;&#41;&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"><span class="elsevierStyleHsp" style=""></span>Myalgia&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">2 &#40;7&#37;&#41;&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">2 &#40;20&#37;&#41;&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">0&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">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cramps&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 &#40;3&#37;&#41;&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">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                      "titulo" => "The pharmacodynamic impact of apremilast&#44; an oral phosphodiesterase 4 inhibitor&#44; on circulating levels of inflammatory biomarkers in patients with psoriatic arthritis&#58; substudy results from a phase III&#44; randomized&#44; placebo-controlled trial &#40;PALACE 1&#41;"
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                    0 => array:2 [
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                      "titulo" => "Apremilast&#44; an oral phosphodiesterase 4 &#40;PDE4&#41; inhibitor&#44; in patients with moderate to severe plaque psoriasis&#58; results of a phase III&#44; randomized&#44; controlled trial &#40;Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis &#91;ESTEEM&#93; 1&#41;"
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