Case and Research Letters
Response to Secukinumab after Treatment Failure with Ustekinumab in 6 Patients with Plaque Psoriasis
Respuesta a secukinumab tras fracaso terapéutico con ustekinumab en seis pacientes con psoriasis en placas
D. Morgado-Carrasco, J. Riera-Monroig, X. Fustà-Novell, M. Alsina Gibert
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Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain
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Morgado-Carrasco, J. Riera-Monroig, X. Fustà-Novell, M. Alsina Gibert" "autores" => array:4 [ 0 => array:2 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Riera-Monroig" ] 2 => array:2 [ "nombre" => "X." "apellidos" => "Fustà-Novell" ] 3 => array:4 [ "nombre" => "M." "apellidos" => "Alsina Gibert" "email" => array:1 [ 0 => "malsina@clinic.cat" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Respuesta a secukinumab tras fracaso terapéutico con ustekinumab en seis pacientes con psoriasis en placas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 828 "Ancho" => 2185 "Tamanyo" => 151810 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Response to treatment with secukinumab in patients with an unacceptable response to treatment with ustekinumab.PASI, Psoriasis Area and Severity Index; SEC, secukinumab.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Secukinumab (SEC) and ustekinumab (UST) are monoclonal antibodies that have both been shown to be highly effective in the treatment of psoriasis,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">1</span></a> although in pivotal studies SEC achieved higher rates of efficacy.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">2</span></a> Their mechanisms of action differ in the target each one blocks in the inflammatory cascade: SEC is an interleukin (IL)-17 inhibitor, while UST blocks IL-12 and IL-23. Clinical trials have demonstrated the efficacy of SEC in patients previously treated with other systemic drugs, including monoclonal antibodies that inhibit tumor necrosis factor (TNF).<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">3</span></a> However, to date there have been no publications about its effectiveness following treatment failure with UST.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Our aim in this study was to assess the efficacy of SEC in patients who had experienced primary or secondary treatment failure with UST, defined respectively as a failure to achieve a 75% reduction in baseline Psoriasis Area and Severity Index (PASI 75) at week 12 or the subsequent loss of such a response. The primary objective was to assess whether patients on SEC had achieved, by week 12, a 90% reduction in baseline PASI (a PASI 90 response), a Physician Global Assessment (PGA) of 1 or less (clear or almost clear), and a Dermatology Life Quality Index (DLQI) of 5 or less. The secondary objective was to assess whether the response was maintained at week 24.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We retrospectively evaluated 6 cases of patients with plaque psoriasis and an inadequate response to prior treatment with UST who were treated with the SEC regimen specified in the Summary of Product Characteristics (complete induction and maintenance with 300<span class="elsevierStyleHsp" style=""></span>mg every 4 weeks). PASI, PGA, and DLQI were measured at baseline and at weeks 12 and 24.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The clinical and epidemiological characteristics of the patients are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. We studied 6 men aged between 32 and 61 years (median, 51 years) with a history of psoriasis of more than 10 years duration (median, 16 years).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the response to treatment with UST and SEC. Treatment failure with UST was primary in 4 patients and secondary in 2. The patients’ PASI scores before starting treatment with SEC ranged from 3.2 to 21 (median, 12.6), the PGA from 3 to 4 (median, 3) and the DLQI from 2 to 25 (median, 13.5). None of the patients received concomitant treatments in addition to SEC. All of the patients presented a reduction in disease activity at week 12 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>): PASI 90 in 66.7% (4/6), and PGA and DLQI of 1 or less in 83.3% (5/6). SEC was withdrawn in 1 patient who did not achieve a PASI 50 response. At week 24, 33.3% (2/6) of the patients had a PASI 90 response, 66.6% (4/6) achieved PASI 75, 50% (3/6) had an absolute PASI of less than 3, and 66.6% (4/6) a PGA and DLQI of less than 1. No significant adverse events were observed during the 24 weeks of treatment with SEC.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In this series of 6 patients in whom treatment with UST had not achieved an acceptable response, 4 patients achieved the primary treatment goal with SEC at week 12. Only 2 patients maintained a PASI 90 response at week 24 (the secondary objective). We used a PASI 90 response as an indicator in line with the current trend towards setting more demanding goals with new biologic therapies. However, most of the patients achieved a PASI 75 response and a PGA 1 or less at weeks 12 and 24, and reported significant improvement in quality of life, reflected by a reduction in DLQI in almost all cases.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The results obtained with SEC were not as good as those reported in the pivotal studies,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">2,3</span></a> a difference that may be due to the inclusion of patients who had previously failed to respond to several systemic therapies, an indication that their condition was difficult to manage. Another possible explanation might be found in the mechanism of action since by inhibiting IL-23, UST indirectly inhibits IL-17.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">4</span></a> Consequently, patients who had failed to respond to UST had already experienced some degree of blockade of the pro-inflammatory IL targeted by SEC without an acceptable clinical response. To further explore this hypothesis, it would be important to assess the response to SEC in patients who fail to respond to treatment with TNF antagonists, which do not inhibit IL-17. However, we found no publications relating to this clinical situation. In the pivotal trials of SEC, fewer than 10% of patients had previously failed to respond to anti-TNF therapy,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">2,3</span></a> and the data relating to this subgroup was unfortunately not analyzed.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Finally, we did not identify any predictors of response to SEC following treatment failure with UST.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The main strengths of this study were the use of multiple clinical response criteria (PASI, PGA and DLQI) before and during biologic therapy and follow-up of the response at 24 weeks. The main limitations were the retrospective nature of the study and the small number of patients included.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion, SEC can be an alternative treatment option in patients who have failed to respond to treatment with UST.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "Références" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Morgado-Carrasco D, Riera-Monroig J, Fustà-Novell X, Gibert MA. Respuesta a secukinumab tras fracaso terapéutico con ustekinumab en seis pacientes con psoriasis en placas. Actas Dermosifiliogr. 2018;109:565–567.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 828 "Ancho" => 2185 "Tamanyo" => 151810 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Response to treatment with secukinumab in patients with an unacceptable response to treatment with ustekinumab.PASI, Psoriasis Area and Severity Index; SEC, secukinumab.</p>" ] ] 1 => 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="spar0015" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: ACI, acitretin; anti-TNF: monoclonal antibody targeting tumor necrosis factor; CIC: ciclosporin; M: man; MTX: methotrexate.</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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sex \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age, y \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Weight, kg \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BMI, kg/m<span class="elsevierStyleSup">2</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Smoking \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Years With Psoriasis \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Psoriatic Arthritis \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Comorbid Conditions \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Prior Systemic Treatment \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">107 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Microscopic colitis, chronic obstructive pulmonary disease, hypertension, heart failure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CIC, MTX \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CIC, MTX, ACI, anti-TNF \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High blood pressure, osteoporosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Leflunomide, anti-TNF \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CIC, MTX, ACI \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MTX \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bronchial asthma, paroxysmal positional vertigo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CIC \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1819471.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Clinical and Epidemiological Characteristics of the Patients.</p>" ] ] 2 => 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:3 [ "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: DLQI, Dermatology Life Quality Index; NT, treatment withdrawn due to lack of response. (failure to achieve PASI 50 by week 12); PASI, Psoriasis Area and Severity Index; PGA, Physician Global Assessment; SEC, secukinumab; UST, ustekinumab.</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="table-head " colspan="3" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment With UST</th><th class="td" title="table-head " colspan="3" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Before Start of SEC</th><th class="td" title="table-head " colspan="4" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SEC Week 12</th><th class="td" title="table-head " colspan="4" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SEC Week 24</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Prior PASI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PASI week 12 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Failure on UST \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PASI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">DLQI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PGA \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PASI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PASI 90 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">DLQI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PGA \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PASI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PASI 90 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">DLQI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PGA \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">43.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Secondary<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">**</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">9.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">22.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Secondary<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">**</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1819470.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Primary failure: failure to achieve a reduction of 75% over baseline PASI (PASI 75) at week 12.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "**" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Secondary failure: loss of PASI 75 response after week 12.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Response to Secukinumab in Patients with Plaque Psoriasis Following Treatment Failure With Ustekinumab.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "Références" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:4 [ 0 => array:3 [ "identificador" => "bib0025" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of systemic long-term treatments for moderate-to-severe psoriasis: A systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Nast" 1 => "A. Jacobs" 2 => "S. Rosumeck" 3 => "R.N. Werner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/jid.2015.206" "Revista" => array:6 [ "tituloSerie" => "J Invest Dermatol." "fecha" => "2015" "volumen" => "135" "paginaInicial" => "2641" "paginaFinal" => "2648" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26046458" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0030" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Thaçi" 1 => "A. Blauvelt" 2 => "K. Reich" 3 => "T.-F. Tsai" 4 => "F. Vanaclocha" 5 => "K. Kingo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2015.05.013" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol." "fecha" => "2015" "volumen" => "73" "paginaInicial" => "400" "paginaFinal" => "409" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26092291" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0035" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Secukinumab in plaque psoriasis —results of two phase 3 trials" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.G. Langley" 1 => "B.E. Elewski" 2 => "M. Lebwohl" 3 => "K. Reich" 4 => "C.E.M. Griffiths" 5 => "K. Papp" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1314258" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med." 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 5 | 4 | 9 |
| 2024 Octubre | 68 | 43 | 111 |
| 2024 Septiembre | 79 | 15 | 94 |
| 2024 Agosto | 99 | 59 | 158 |
| 2024 Julio | 85 | 31 | 116 |
| 2024 Junio | 89 | 25 | 114 |
| 2024 Mayo | 95 | 27 | 122 |
| 2024 Abril | 91 | 22 | 113 |
| 2024 Marzo | 79 | 23 | 102 |
| 2024 Febrero | 64 | 22 | 86 |
| 2024 Enero | 83 | 31 | 114 |
| 2023 Diciembre | 48 | 19 | 67 |
| 2023 Noviembre | 70 | 22 | 92 |
| 2023 Octubre | 66 | 33 | 99 |
| 2023 Septiembre | 47 | 48 | 95 |
| 2023 Agosto | 43 | 20 | 63 |
| 2023 Julio | 47 | 33 | 80 |
| 2023 Junio | 43 | 23 | 66 |
| 2023 Mayo | 53 | 30 | 83 |
| 2023 Abril | 26 | 22 | 48 |
| 2023 Marzo | 33 | 24 | 57 |
| 2023 Febrero | 46 | 24 | 70 |
| 2023 Enero | 27 | 18 | 45 |
| 2022 Diciembre | 40 | 43 | 83 |
| 2022 Noviembre | 32 | 29 | 61 |
| 2022 Octubre | 39 | 22 | 61 |
| 2022 Septiembre | 26 | 48 | 74 |
| 2022 Agosto | 29 | 55 | 84 |
| 2022 Julio | 26 | 47 | 73 |
| 2022 Junio | 22 | 32 | 54 |
| 2022 Mayo | 26 | 49 | 75 |
| 2022 Abril | 53 | 34 | 87 |
| 2022 Marzo | 36 | 59 | 95 |
| 2022 Febrero | 45 | 40 | 85 |
| 2022 Enero | 71 | 45 | 116 |
| 2021 Diciembre | 37 | 39 | 76 |
| 2021 Noviembre | 41 | 41 | 82 |
| 2021 Octubre | 45 | 56 | 101 |
| 2021 Septiembre | 32 | 41 | 73 |
| 2021 Agosto | 55 | 29 | 84 |
| 2021 Julio | 42 | 23 | 65 |
| 2021 Junio | 22 | 28 | 50 |
| 2021 Mayo | 44 | 41 | 85 |
| 2021 Abril | 66 | 80 | 146 |
| 2021 Marzo | 53 | 25 | 78 |
| 2021 Febrero | 56 | 23 | 79 |
| 2021 Enero | 36 | 17 | 53 |
| 2020 Diciembre | 32 | 23 | 55 |
| 2020 Noviembre | 11 | 22 | 33 |
| 2020 Octubre | 29 | 10 | 39 |
| 2020 Septiembre | 34 | 13 | 47 |
| 2020 Agosto | 33 | 23 | 56 |
| 2020 Julio | 33 | 18 | 51 |
| 2020 Junio | 23 | 31 | 54 |
| 2020 Mayo | 22 | 26 | 48 |
| 2020 Abril | 48 | 18 | 66 |
| 2020 Marzo | 19 | 10 | 29 |
| 2020 Febrero | 2 | 0 | 2 |
| 2019 Septiembre | 1 | 2 | 3 |
| 2019 Mayo | 0 | 1 | 1 |
| 2019 Abril | 1 | 0 | 1 |
| 2019 Febrero | 6 | 2 | 8 |
| 2018 Julio | 0 | 1 | 1 |
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