Research Letter
Therapeutic response and survival time of immunobiologicals in patients with moderate to severe psoriasis
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(A), Primeira linha (naïve) (p <<span class="elsevierStyleHsp" style=""></span>0,001); (B), Segunda linha (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,003) em dois anos (730 dias). Nos grupos de primeira e segunda linha, o ustequinumabe apresenta maior probabilidade de sobrevida da droga em dois anos: 89,2% e 83,3% respectivamente. O infliximabe mostra menor probabilidade de sobrevida da droga em dois anos nos grupos de primeira e segunda linha (26,1% e 12,5%, respectivamente), com mais falhas). Por meio da análise dos prontuários foi possível avaliar a sobrevida de alguns imunobiológicos pelo período de até 10 anos (3650 dias). UST, ustequinumabe; SEC, secuquinumabe; ADA, adalimumabe; ETA, etanercepte;INF, infliximabe.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Cynthia Cristina Ferreira Mota, Ricardo Romiti, Marcelo Arnone, Andre Luís da Silva Hirayama, Maria Denise Fonseca Takahashi" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Cynthia Cristina Ferreira" "apellidos" => "Mota" ] 1 => array:2 [ "nombre" => "Ricardo" "apellidos" => "Romiti" ] 2 => array:2 [ "nombre" => "Marcelo" "apellidos" => "Arnone" ] 3 => array:2 [ "nombre" => "Andre Luís da Silva" "apellidos" => "Hirayama" ] 4 => array:2 [ "nombre" => "Maria Denise Fonseca" "apellidos" => "Takahashi" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0365059621002658" "doi" => "10.1016/j.abd.2021.03.008" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059621002658?idApp=UINPBA00008Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275221002769?idApp=UINPBA00008Z" "url" => "/26662752/0000009700000001/v1_202202030913/S2666275221002769/v1_202202030913/pt/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S0365059621002646" "issn" => "03650596" "doi" => "10.1016/j.abd.2020.10.013" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "472" "copyright" => "Sociedade Brasileira de Dermatologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by/4.0/" "subdocumento" => "sco" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Research Letter</span>" "titulo" => "Trends in melanoma incidence at Hospital Italiano de Buenos Aires, 2007–2016" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "115" "paginaFinal" => "117" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2744 "Ancho" => 1681 "Tamanyo" => 304543 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Gender and age distribution of (A), Italian Hospital Medical Care Program and (B), Buenos Aires, population according to 2010 national demographic census. 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This chart reflects a better performance of secukinumab, followed by UST (second place), ADA (third place), ETA (fourth place), and INF (fifth place) over the period of 2 years (730 days). Through the analysis of the medical records, it was possible to assess the survival of some immunobiologicals for a period of up to 10 years (3,650 days).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Psoriasis is an inflammatory, chronic and recurrent disease with evident genetic influence. The intensity, extension and different manifestations associated with the disease guide therapeutic decisions. Advances in the knowledge of the disease immunopathology over the last decades have culminated in the development of new medications, called immunobiologicals, which act in a specific and precise way at different levels of the inflammatory cascade of psoriasis.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> With the introduction of anti-tumor necrosis factor-alpha (anti-TNF-α) drugs: etanercept (ETA), infliximab (INF), adalimumab (ADA), and certolizumab pegol (CP), followed by inhibitors of interleukin-12/23, ustekinumab (UST); inhibitors of interleukin 17: secukinumab (SEC) and Ixekizumab (IXE), and more recently inhibitors of interleukin 23 alone: ​​ Guselkumab (GUS) and Risankizumab (RISA), it has become possible to effectively treat severe and refractory forms of the disease, associated with a satisfactory safety profile. On the other hand, uncertainty regarding the choice of the most appropriate drug, the long-term sustained response, and the possibility of interrupting therapy has an impact on the therapeutic decision.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Drug survival is defined as the time from the beginning to the discontinuation of a certain treatment. The time interval from the start of the treatment to its discontinuation, as well as the reasons for this outcome, whether due to loss of efficacy, complications, or treatment abandonment, may vary in different populations with psoriasis.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> To date, there are no data associating the therapeutic response to the survival time of immunobiologicals in patients with psoriasis in Brazil.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Aiming to determine the time of drug survival, a total of 229 treatments with immunobiological drugs were evaluated in 110 patients with moderate to severe psoriasis at Hospital das Clínicas, Universidade de São Paulo, in the state of São Paulo, Brazil, for a period of two years and analysed regarding the response to immunobiologicals, number of previous treatments and reason for discontinuation. The analysis of medical records also allowed the collection of data in relation to previous treatments since the introduction of immunobiologicals as a therapeutic option. Drug survival was defined as the time from the start of the treatment with the immunobiological, that is, the first dose until the occurrence of the event of interest (temporary/definitive discontinuation of treatment). Kaplan-Meier curves were used to estimate each of the drug survival probabilities and the difference between the drug survival curves was verified using the logrank test.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The comparative analysis between the five immunobiologicals showed that SEC was the drug with the longest time of survival, including 22 treatments (9.6%), followed by UST with 64 treatments (28%), ADA with 52 treatments (22.7%), ETA with 56 treatments (24.4%), and INF with 35 treatments (15.3%) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Second-line cases showed lower drug survival compared to first-line cases, whereas third-line cases had lower survival compared to second-line cases, and so forth. Isolated analyses regarding the first and second-line drugs depicted Kaplan-Meier curves showing that UST had a higher probability of drug survival, with fewer failures. INF showed a lower probability of drug survival in two years, with more failures. These differences were shown to be statistically significant (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Among the factors that led to treatment interruption, present in 95 of a total of 229 treatments (41.5%), the most frequent cause of temporary interruption was the lack of medication supply, observed in 76 of the analyzed cases (33.2%) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), whereas among the causes of definitive interruption, observed in 123 of a total of 229 treatments (49.6%), the main cause was a secondary treatment failure, observed in 26.6% of the analyzed treatments (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Overall, the primary failure was considered when the patient did not show a PASI50 response after 24 weeks of treatment and occurred in 5.2% of cases. When analyzing the results, one should consider the small number of cases treated with SEC, a drug that was only approved in Brazil in 2016. Similarly, data from more recently approved immunobiologicals such as CP, IXE, GUS, and RISA are not included in the results of this study.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">According to the literature, one of the main causes for the discontinuation of an immunobiological is the loss of efficacy, also called secondary failure.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> Our results demonstrate in an unprecedented way that the medication supply failure was the main reason for the temporary interruption of treatments. It is noteworthy that, when resuming the immunobiological treatment after a prolonged interruption, the chance of a lower response should always be considered.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> These facts reinforce the importance and need for continuous and regular provision of these medications by the providers.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The occurrence of tuberculosis leading to treatment discontinuation was exclusive to anti-TNFs, as well as the few cases of infusion reaction, UAIs, hepatotoxicity, and cancer. The lack of medication in the Brazilian Unified Health System (SUS, <span class="elsevierStyleItalic">Sistema Único de Saúde</span>), leading to the definitive interruption of the therapy, was more frequent with UST and SEC. Regarding the main cause of discontinuation, secondary failure occurred with all immunobiologicals, with a variation only in the time of its occurrence.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The results shown here provide a regional analysis of the time of survival of immunobiological drugs and the main reasons for treatment discontinuation in a public institution, which can help in the planning and monitoring of treatments with immunobiologicals, both by the prescribing physicians and the health managers.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0045" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors’ contributions</span><p id="par0050" class="elsevierStylePara elsevierViewall">Cynthia Cristina Ferreira Mota: Terminology, conceptualization, methodology, investigation, resources, data curation, writing-original draft, visualization, project administration.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Ricardo Romiti: Methodology, investigation, writing review and editing, supervision.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Marcelo Arnone: Investigation.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Andre Luís da Silva Hirayama: Investigation.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Maria Denise Fonseca Takahashi: Investigation.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Financial support" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Authors’ contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-12-03" "fechaAceptado" => "2021-03-04" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Study conducted at the Hospital das Clínicas da Universidade de São Paulo, São Paulo, SP, Brazil.</p>" ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1285 "Ancho" => 2167 "Tamanyo" => 158334 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier curve for all treatments (p < 0.001). This chart reflects a better performance of secukinumab, followed by UST (second place), ADA (third place), ETA (fourth place), and INF (fifth place) over the period of 2 years (730 days). Through the analysis of the medical records, it was possible to assess the survival of some immunobiologicals for a period of up to 10 years (3,650 days).</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1333 "Ancho" => 3174 "Tamanyo" => 279642 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier curves for the treatments. (A), first-line (naïve) (p < 0.001); (B), Second-line (p = 0.003) in two years (730 days). In the first- and second-line groups, UST shows a higher probability of drug survival in two years; 89.2% and 83.3% respectively. INF shows a lower probability of drug survival in two years in the first and second-line groups (26.1% and 12.5%, respectively), with more failures. Through the analysis of the medical records, it was possible to assess the survival of some immunobiologicals for a period of up to 10 years (3,650 days).</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">SUS, <span class="elsevierStyleItalic">Sistema Único de Saúde</span>; UAIs, Upper Airway Infections.</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"> \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">Reasons \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">n (%) \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 rowgroup " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 229 Treatments</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">Failure of supply in SUS \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">76 (33.2) \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">Others<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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">9 (3.9) \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">Pregnancy \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 (1.3) \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">Lost to follow-up \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 (1.3) \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">Surgery \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 (0.9) \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">Repeated UAIs \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 (0.9) \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">Total \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"> \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">95 (41.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2810845.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Others: Nonspecific symptoms such as headache, myalgia, arthralgia, nausea.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Reasons for temporary interruption of treatments.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Others, Headache, nausea, myalgia, and arthralgia; SUS, Unified Health System; Protocol, Patients who used infliximab only in the induction phase to control erythrodermic psoriasis; UAI, Upper Airway Infection.</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"> \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">Reasons \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">n (%) \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 rowgroup " rowspan="12" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 229 Treatments</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">Secondary failure \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">61 (26,6) \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">Others \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 (8,3) \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">Primary failure \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 (5,2) \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">Failure of supply in SUS \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 (5,2) \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">Tuberculosis \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 (3,5) \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">Pregnancy \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 (1,7) \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">Protocol \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 (0,9) \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">Stomach cancer \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 (0,4) \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">Hernia surgery \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 (0,4) \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">Hepatotoxicity \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 (0,4) \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">UAI \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 (0.4) \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">Infusion reaction \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 (0.4) \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">Total \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"> \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">123 (53.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2810844.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Reasons for definitive interruption of treatments.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Psoriasis: from pathogenesis to targeted therapies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 2 | 9 |
| 2024 October | 94 | 69 | 163 |
| 2024 September | 143 | 92 | 235 |
| 2024 August | 147 | 114 | 261 |
| 2024 July | 148 | 103 | 251 |
| 2024 June | 119 | 63 | 182 |
| 2024 May | 112 | 59 | 171 |
| 2024 April | 125 | 82 | 207 |
| 2024 March | 107 | 65 | 172 |
| 2024 February | 109 | 75 | 184 |
| 2024 January | 76 | 47 | 123 |
| 2023 December | 66 | 55 | 121 |
| 2023 November | 81 | 80 | 161 |
| 2023 October | 64 | 83 | 147 |
| 2023 September | 79 | 72 | 151 |
| 2023 August | 62 | 37 | 99 |
| 2023 July | 58 | 41 | 99 |
| 2023 June | 78 | 55 | 133 |
| 2023 May | 63 | 19 | 82 |
| 2023 April | 46 | 19 | 65 |
| 2023 March | 71 | 54 | 125 |
| 2023 February | 43 | 38 | 81 |
| 2023 January | 55 | 58 | 113 |
| 2022 December | 63 | 43 | 106 |
| 2022 November | 79 | 59 | 138 |
| 2022 October | 163 | 73 | 236 |
| 2022 September | 58 | 64 | 122 |
| 2022 August | 48 | 42 | 90 |
| 2022 July | 56 | 60 | 116 |
| 2022 June | 53 | 57 | 110 |
| 2022 May | 75 | 61 | 136 |
| 2022 April | 54 | 61 | 115 |
| 2022 March | 67 | 76 | 143 |
| 2022 February | 94 | 52 | 146 |
| 2022 January | 130 | 92 | 222 |
| 2021 December | 30 | 53 | 83 |
| 2021 November | 11 | 15 | 26 |
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