RESUMO
BACKGROUND: Palmoplantar plaque psoriasis is a frequent clinical subtype of childhood psoriasis. This study evaluated the effectiveness of biologic therapies in children with palmoplantar plaque psoriasis using data from the two Biological treatments for Pediatric Psoriasis (BiPe) cohorts. METHODS: Data for all 170 patients included in the BiPe cohorts were analyzed. Data on the effectiveness (PGA, PASI between baseline and 3 months of treatment) of biologic therapies were then compared between children with palmoplantar plaque psoriasis (n = 20) and those with generalized plaque psoriasis (n = 136). Clinical and demographic data were also analyzed. RESULTS: Children in the palmoplantar group were more likely to be male (p = .04), with an earlier age of psoriasis onset (p < .001), and more frequent nail involvement (p < .001). After 3 months of biologic treatment, mean PGA scores were higher in the palmoplantar group than in the generalized plaque psoriasis group (p = .004). In the palmoplantar group, continuation rates were higher for adalimumab than for etanercept or ustekinumab (p = .01). Primary inefficacy was a more frequent reason for stopping biologic therapies in the palmoplantar group (p = .01), and disease remission was less frequent (p = .05). Combined systemic and biologic therapies were more frequently used in palmoplantar plaque psoriasis (p < .001). CONCLUSIONS: This study demonstrated the treatment-resistant nature of palmoplantar plaque psoriasis and indicated that adalimumab could be the most effective biologic treatment. Larger studies are needed to allow therapeutic algorithms for palmoplantar plaque psoriasis to be proposed in pediatric psoriasis management guidelines.
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Produtos Biológicos , Psoríase , Humanos , Masculino , Criança , Feminino , Adalimumab/uso terapêutico , Psoríase/tratamento farmacológico , Etanercepte/uso terapêutico , Ustekinumab/uso terapêutico , Terapia Biológica , Resultado do Tratamento , Produtos Biológicos/uso terapêutico , Índice de Gravidade de DoençaRESUMO
Combined therapies involve the use of multiple drugs to increase efficacy and reduce the toxicity of individual treatments. We evaluated the use of combinations of conventional systemic therapies and biologics in children with psoriasis in daily practice. This two-part study used data from the 170 children in the Franco-Italian BiPe cohorts to evaluate the use, efficacy, and safety of combined conventional systemic-biologic therapies, and from a survey carried out among French and Italian dermatologists to better understand the reasons for using or avoiding these combinations. In total, 33 children (19.4%) from 13 dermatology centers received 48 combined conventional systemic-biologic therapies (cumulative duration: 43.6 years), including three triple combination therapies (acitretin-methotrexate, with a TNF-alpha inhibitor). A total of 14 different combinations were used, most frequently etanercept-acitretin (n = 10), adalimumab-acitretin (n = 7), adalimumab-methotrexate (n = 5), and ustekinumab-methotrexate (n = 5). The combined therapies were started at biologic initiation in 41 cases (85.4%), and after a period of biologic monotherapy in the remaining 7 cases. Mean PGA and PASI scores decreased between baseline and M3 with all the combinations used. Four serious adverse events were reported, all with favorable outcomes. The survey was completed by 61 dermatologists: 39 (63.9%) had previously used or planned to use the combined therapies, most commonly TNF-alpha inhibitors with acitretin or methotrexate. The main reason for using these treatments was to improve the outcome of biologic therapies in cases of partial efficacy or loss of efficacy. Combined therapies have been used frequently in the treatment of childhood psoriasis, in a range of clinical situations and in variable drug combinations, without significant toxicity. Although the use of these combined therapies needs to be clarified in future management guidelines, these combined therapies should be considered for the treatment of children with severe psoriasis, psoriatic arthritis, and recalcitrant disease.
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Produtos Biológicos , Fármacos Dermatológicos , Psoríase , Criança , Humanos , Acitretina/efeitos adversos , Acitretina/uso terapêutico , Adalimumab/efeitos adversos , Adalimumab/uso terapêutico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Dermatologistas , Etanercepte/efeitos adversos , Etanercepte/uso terapêutico , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Psoríase/tratamento farmacológico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
BACKGROUND: There is currently little information on switching biologics in pediatric psoriasis. OBJECTIVE: To evaluate the real-world clinical practice and safety of switching biologics in the "Biological Treatments for Pediatric Psoriasis" (BiPe) cohort. METHODS: Data for all 134 patients included in the BiPe cohort were analyzed. A further evaluation of the subpopulation of patients who switched from a first-line biologic to a second-line biologic was then conducted. Drug survival rates were also compared between biologics given as first-line or second-line agents. RESULTS: Overall, 29 patients (female: 55%; mean age: 16.6 ± 3.0 years) switched between two biologics. Etanercept (ETN) was the first-line biologic used in 23 patients: 16 (69.6%) switched to adalimumab (ADA) and seven (30.4%) to ustekinumab (UST). Six patients received first-line ADA and switched to UST. Loss of efficacy (62.1%), primary inefficacy (20.7%), and parental choice (6.9%) were the main reasons for switching biologics. One (3.4%) of the switches was performed because of adverse events or intolerance. For UST and ADA, the 18-month drug survival rate did not differ according to whether the agent was given as a first-line or second-line biologic (UST: P = .24; ADA: P = .68). No significant differences in drug survival rates were observed between the three different switches (ADA to UST, ETN to ADA, and ETN to UST). CONCLUSION: Our study provided key insights into the real-life clinical practice of switching biologics in pediatric psoriasis patients. However, more information and guidance on switching biologics in pediatric psoriasis are needed to improve real-life practice and outcomes.
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Produtos Biológicos , Psoríase , Adalimumab/efeitos adversos , Adolescente , Adulto , Produtos Biológicos/efeitos adversos , Criança , Etanercepte/efeitos adversos , Feminino , Humanos , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Ustekinumab/uso terapêutico , Adulto JovemRESUMO
Anti-interleukin-17 agents have recently been developed for the treatment of psoriasis. This study evaluated the tolerance and effectiveness of anti-interleukin-17 agents for psoriasis in elderly patients in daily practice. A multicentre, retrospective study was performed, involving psoriatic patients aged ≥65 years who had received an anti-interleukin-17 agent, including secukinumab, ixekizumab or brodalumab. A total of 114 patients were included: 72 received secukinumab, 35 ixekizumab, and 7 brodalumab. Treatment was stopped in 32 patients (28.9%), because of relapses in 14 patients (41.2%), primary failures in 11 patients (32.4%), or adverse events in 7 patients (20.6%). The 3 most frequently reported adverse events were injection site reactions (n = 4), oral candidiasis (n = 3), and influenza-like illness (n = 3). Regarding effectiveness, 80 patients (70%) reached a Physician Global Assessment score of 0/1, 6 months after treatment initiation. In conclusion, anti-interleukin-17 therapy appears to be an effective and safe therapeutic option for psoriasis treatment in patients aged ≥ 65 years.
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Anticorpos Monoclonais , Psoríase , Idoso , Anticorpos Monoclonais/efeitos adversos , Humanos , Imunoterapia , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis. This is the baseline update of a Cochrane Review first published in 2017, in preparation for this Cochrane Review becoming a living systematic review. OBJECTIVES: To compare the efficacy and safety of conventional systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis, and to provide a ranking of these treatments according to their efficacy and safety. SEARCH METHODS: We updated our research using the following databases to January 2019: the Cochrane Skin Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS and the conference proceedings of a number of dermatology meetings. We also searched five trials registers and the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) reports (until June 2019). We checked the reference lists of included and excluded studies for further references to relevant RCTs. SELECTION CRITERIA: Randomised controlled trials (RCTs) of systemic treatments in adults (over 18 years of age) with moderate-to-severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate-to-severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. The primary outcomes of this review were: the proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90 at induction phase (from 8 to 24 weeks after the randomisation), and the proportion of participants with serious adverse effects (SAEs) at induction phase. We did not evaluate differences in specific adverse effects. DATA COLLECTION AND ANALYSIS: Several groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the PASI 90 score) and acceptability (the inverse of serious adverse effects). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes, according to GRADE, as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing. MAIN RESULTS: We included 140 studies (31 new studies for the update) in our review (51,749 randomised participants, 68% men, mainly recruited from hospitals). The overall average age was 45 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo-controlled (59%), 30% were head-to-head studies, and 11% were multi-armed studies with both an active comparator and a placebo. We have assessed a total of 19 treatments. In all, 117 trials were multicentric (two to 231 centres). All but two of the outcomes included in this review were limited to the induction phase (assessment from 8 to 24 weeks after randomisation). We assessed many studies (57/140) as being at high risk of bias; 42 were at an unclear risk, and 41 at low risk. Most studies (107/140) declared funding by a pharmaceutical company, and 22 studies did not report the source of funding. Network meta-analysis at class level showed that all of the interventions (conventional systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in terms of reaching PASI 90. At class level, in terms of reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents. At drug level, in terms of reaching PASI 90, infliximab, all of the anti-IL17 drugs (ixekizumab, secukinumab, bimekizumab and brodalumab) and the anti-IL23 drugs (risankizumab and guselkumab, but not tildrakizumab) were significantly more effective in reaching PASI 90 than ustekinumab and 3 anti-TNF alpha agents: adalimumab, certolizumab and etanercept. Adalimumab and ustekinumab were significantly more effective in reaching PASI 90 than certolizumab and etanercept. There was no significant difference between tofacitinib or apremilast and between two conventional drugs: ciclosporin and methotrexate. Network meta-analysis also showed that infliximab, ixekizumab, risankizumab, bimekizumab, guselkumab, secukinumab and brodalumab outperformed other drugs when compared to placebo in reaching PASI 90. The clinical effectiveness for these seven drugs was similar: infliximab (versus placebo): risk ratio (RR) 29.52, 95% confidence interval (CI) 19.94 to 43.70, Surface Under the Cumulative Ranking (SUCRA) = 88.5; moderate-certainty evidence; ixekizumab (versus placebo): RR 28.12, 95% CI 23.17 to 34.12, SUCRA = 88.3, moderate-certainty evidence; risankizumab (versus placebo): RR 27.67, 95% CI 22.86 to 33.49, SUCRA = 87.5, high-certainty evidence; bimekizumab (versus placebo): RR 58.64, 95% CI 3.72 to 923.86, SUCRA = 83.5, low-certainty evidence; guselkumab (versus placebo): RR 25.84, 95% CI 20.90 to 31.95; SUCRA = 81; moderate-certainty evidence; secukinumab (versus placebo): RR 23.97, 95% CI 20.03 to 28.70, SUCRA = 75.4; high-certainty evidence; and brodalumab (versus placebo): RR 21.96, 95% CI 18.17 to 26.53, SUCRA = 68.7; moderate-certainty evidence. Conservative interpretation is warranted for the results for bimekizumab (as well as tyrosine kinase 2 inhibitor, acitretin, ciclosporin, fumaric acid esters, and methotrexate), as these drugs, in the NMA, have been evaluated in few trials. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. Nevertheless, the SAE analyses were based on a very low number of events with low to very low certainty for just under half of the treatment estimates in total, and moderate for the others. Thus, the results have to be viewed with caution and we cannot be sure of the ranking. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1) the results were very similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions. AUTHORS' CONCLUSIONS: Our review shows that compared to placebo, the biologics infliximab, ixekizumab, risankizumab, bimekizumab, guselkumab, secukinumab and brodalumab were the best choices for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of moderate- to high-certainty evidence (low-certainty evidence for bimekizumab). This NMA evidence is limited to induction therapy (outcomes were measured from 8 to 24 weeks after randomisation) and is not sufficient for evaluation of longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean age of 45 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice. Another major concern is that short-term trials provide scanty and sometimes poorly-reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs, but the evidence for all the interventions was of very low to moderate quality. In order to provide long-term information on the safety of the treatments included in this review, it will also be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies. In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve participants, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunossupressores/uso terapêutico , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Doença Crônica , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Humanos , Terapia de Alvo Molecular , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresAssuntos
Dermatite/diagnóstico , Dermatologistas , Hidradenite Supurativa/diagnóstico , Psoríase/diagnóstico , Autorrelato , Vitiligo/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Dermatologistas/psicologia , Feminino , França , Humanos , Julgamento , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto JovemRESUMO
INTRODUCTION: Biological therapies are valuable treatments for severe psoriasis. Children aged under 12 years are underrepresented in therapeutic trials for these drugs. The objective of the 'BiPe Jr' cohort study was to evaluate the drug survival, effectiveness, tolerance and switching patterns of biological therapies in children under 12 years of age with psoriasis. METHODS: We conducted a multicentre retrospective study of children with psoriasis who received at least one injection of a biological agent, even off-licence, before the age of 12 years in France and Italy, collecting the data between April and August 2021. The data collected were from March 2012 up to August 2021. RESULTS: In total, 82 children (mean age: 9.1 years; females: 61.0%) received 106 treatments. The drugs administered were adalimumab (n = 49), etanercept (n = 37), ustekinumab (n = 15), anakinra (n = 2), infliximab (n = 2) and secukinumab (n = 1). The most common form of psoriasis was plaque psoriasis (62.9%). The Physician Global Assessment and the Psoriasis Area Severity Index (PASI) scores decreased significantly from baseline to 3 months after treatment initiation for the three main biological drugs; PASI went from 14.1 ± 9.4 to 4.1 ± 11.3 for adalimumab (p = 0.001), 14.9 ± 9.3 to 5.1 ± 4.0 for etanercept (p = 0.002) and 11.6 ± 8.3 to 2.6 ± 2.2 for ustekinumab (p = 0.007). A trend towards higher 2-year maintenance rates was observed for ustekinumab and adalimumab, compared with etanercept (p = 0.06). 52 children discontinued their biological therapy, most frequently due to inefficacy (n = 28) and remission (n = 14). Seven serious adverse events (SAEs) were reported, including four severe infections. DISCUSSION: Our analyses of drug survival and treatment patterns, combined with those of previous studies conducted in older children, indicate that there is a trend towards higher 2-year survival rates of ustekinumab and adalimumab. The SAEs identified were rare, but highlight the need for increased vigilance concerning infections. Overall, the biological therapies showed good effectiveness and safety profiles when used in daily practice for the treatment of young children with psoriasis.
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Psoríase , Ustekinumab , Adalimumab/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Etanercepte , Feminino , Humanos , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab/efeitos adversosAssuntos
Percevejos-de-Cama , Eosinofilia , Eritema , Mordeduras e Picadas de Insetos , Idoso , Animais , Astenia , Conjuntivite , Eosinofilia/diagnóstico , Eosinofilia/etiologia , Eosinofilia/fisiopatologia , Eritema/diagnóstico , Eritema/etiologia , Eritema/fisiopatologia , Humanos , Mordeduras e Picadas de Insetos/complicações , Mordeduras e Picadas de Insetos/diagnóstico , Mordeduras e Picadas de Insetos/fisiopatologia , MasculinoRESUMO
INTRODUCTION: Psoriasis affects about 0.5% of children and adolescents, it has a high impact of social life. Management can be difficult. The beginning of the 21st century has been an interesting period for the management of pediatric psoriasis, with access to new topical and systemic treatments including several biotherapies. AREAS COVERED: Herein, we analyze the current therapeutic strategies for managing psoriasis in young patients, ranging from infants to adolescents, in a holistic approach. Usual treatment but also new galenics, new topical associations, and biological (anti-TNF-alpha, anti-interleukin 12/23, anti-interleukin 17) recently developed are presented. Results from clinical trials are detailed, but also real-world evaluations, and recent guidelines. Practical tips for day-to-day management are finally proposed. EXPERT OPINION: Currently, we have a wide range of treatments, which we can adapt to all types of psoriasis, depending on the demands of the child and his parents. The near future also looks promising with new topical combinations, new oral therapies (apremilast) and biologics (anti-interleukin 23), as well as genetically targeted therapies for pustular psoriasis.
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Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Administração Cutânea , Administração Oral , Adolescente , Fatores Biológicos/administração & dosagem , Fatores Biológicos/farmacologia , Criança , Pré-Escolar , Fármacos Dermatológicos/farmacologia , Humanos , Lactente , Psoríase/patologiaRESUMO
We sought to assess the quality of dermatological systematic reviews (SRs) and identify factors that predict high methodological quality. We searched for all SRs published in 2017 using PubMed, Epistemonikos, and the Cochrane Database of SRs. We included studies identified as SRs or meta-analysis in the title or abstract and dealing with a dermatological topic. Study selection and data extraction were carried out and Preferred Reporting Items for SRs and Meta-Analyses and rating by A MeaSurement Tool to Assess SRs 2 were used independently by two authors. On the basis of A MeaSurement Tool to Assess SRs 2, confidence in SRs results was classified as high, moderate, low, or very low. We included 732 studies. We described a random sample of 140. The overall rating of confidence in the results according to a tool called A MeaSurement Tool to Assess SRs 2 was high or moderate for nine reviews (6%). A total of 20 reviews (15%) had a registered protocol. Independent factors associated with moderate or high rating of A MeaSurement Tool to Assess SRs 2 were publication in a journal where Preferred Reporting Items for SRs and Meta-Analyses was mandatory (OR [95% confidence interval] = 27.0 [1.4-528]) and journal impact factor (OR of 1.9 [1.3-3]) for each increase in one more point. The observation that 90% of published dermatology SRs are of very low quality is alarming. Review registration in the International Prospective Register of SRs and full reporting according to Preferred Items for SRs and Meta-Analyses should be mandatory for publication. This study is registered in the International Prospective Register of SRs (CRD42018093856).
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Dermatologia/normas , Melhoria de Qualidade , Bases de Dados Factuais , HumanosRESUMO
INTRODUCTION: Apremilast is a drug recently developed for psoriasis. Few data are available on its use in the elderly. We evaluated the tolerance and effectiveness of apremilast used in daily practice for psoriasis treatment in older patients. METHODS: We performed a multicenter, retrospective study involving patients aged ≥ 65 years who had received apremilast as a psoriasis treatment. Demographic data and details regarding psoriasis and adverse events (AEs) were collected from patient medical records. RESULTS: 135 patients were included (mean age: 73.5 years). Treatment was stopped in 74 patients (54.8%) for AEs (n = 43, 56.6%), primary failures (n = 18, 23.4%), and relapses (n = 7, 9.2%). When patients were stratified by age at treatment initiation, the main cause of discontinuation in patients ≥ 75 years was AEs, whereas in patients aged 65-74 years it was primary failures (28.3%). Sixty-one patients reported AEs, mainly digestive (n = 49). Regarding effectiveness, 45.2% of patients reached PGA 0/1 between 3 and 6 months after treatment initiation. One-year apremilast continuation rates were better in the 65-74 and 75-84 years subgroups than in the > 85 years subgroup (p = 0.01). CONCLUSION: Apremilast seems to be an effective and safe therapeutic option for psoriasis in the elderly. The main AEs reported by patients did not seem to differ from those reported previously in younger populations. However, AEs were more frequent in patients > 75 years old leading to more frequent discontinuation of apremilast compared with younger patients, suggesting a higher level of vigilance is needed in the elderly.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Psoríase/tratamento farmacológico , Talidomida/análogos & derivados , Administração Oral , Fatores Etários , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Feminino , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Inibidores da Fosfodiesterase 4/administração & dosagem , Inibidores da Fosfodiesterase 4/efeitos adversos , Estudos Retrospectivos , Índice de Gravidade de Doença , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Phase III clinical trials of biotherapies for childhood psoriasis are designed for a selected population, which can differ from real-life patients. OBJECTIVE: Our objective was to assess the proportion of children with psoriasis that received biotherapy in the biological treatments for pediatric psoriasis (BiPe) cohort that would be excluded from phase III clinical trials of these treatments. METHODS: Data concerning initiation of the first biotherapy from all patients included in the BiPe cohort were analyzed. Ineligibility was assessed after applying the exclusion criteria used in the principal phase III trials of etanercept, adalimumab, and ustekinumab for childhood psoriasis. RESULTS: Of the 134 patients included, 73 (54.5%) were ineligible for at least one randomized controlled trial based on one or more exclusion criteria. Amongst the 63 children treated with etanercept, 35 (55.5%) were ineligible: 22 because of the type of psoriasis, 12 because of concomitant treatment, and six because of psoriasis severity based on psoriasis assessment severity index (PASI) and physician global assessment (PGA) scores (PASI < 12 and PGA < 3). Amongst the 44 children treated with adalimumab, 32 (72.7%) were ineligible: 17 because of the clinical type of psoriasis, 12 because of psoriasis severity (PASI < 20 and PGA < 4), and seven because of concomitant treatment. Amongst the 27 children patients treated with ustekinumab, 12 (44.4%) were ineligible: eight because of psoriasis severity (PASI < 12 and PGA < 3), five because of the clinical type of psoriasis, and one because of concomitant treatment. Drug survival and the frequency of serious adverse events did not differ between eligible and ineligible patients. CONCLUSION: The majority of children treated with biotherapies in real-life practice differ from those in phase III trials, most commonly because of the clinical type of their psoriasis, the disease severity being lower than required and the use of prior or concomitant psoriasis treatment. Efficacy and safety results from phase III clinical trials in selected populations may not sufficiently reflect what is seen in real life, thus results from real-life cohort studies are necessary.
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Terapia Biológica/métodos , Psoríase/tratamento farmacológico , Adolescente , Feminino , Humanos , Masculino , Resultado do TratamentoRESUMO
Importance: Psoriasis is a chronic inflammatory disease. The Mediterranean diet has been shown to reduce chronic inflammation and has a positive effect on the risk of metabolic syndrome and cardiovascular events. Thus, we hypothesized a positive effect on the onset and/or severity of psoriasis. Objective: To assess the association between a score that reflects the adhesion to a Mediterranean diet (MEDI-LITE) and the onset and/or severity of psoriasis. Design, Setting, and Participants: The NutriNet-Santé program is an ongoing, observational, web-based questionnaire cohort study launched in France in May 2009. The present study was performed within the framework of the NutriNet-Santé program, with data collected and analyzed between April 2017 and June 2017. Patients with psoriasis were identified via a validated online self-completed questionnaire and then categorized by disease severity: severe psoriasis, nonsevere psoriasis, and psoriasis-free. Data on dietary intake (including alcohol) were gathered during the first 2 years of participation in the cohort to calculate the MEDI-LITE score (ranging from 0 for no adherence to 18 for maximum adherence). Potentially confounding variables (eg, age, sex, physical activity, body mass index, tobacco use, and a history of cardiovascular disease) were also recorded. Analyses used adjusted multinomial logistic regression to estimate the risk of having severe psoriasis or nonsevere psoriasis compared with being psoriasis-free. Results: Of the 158â¯361 total NutriNet-Santé participants, 35â¯735 (23%) replied to the psoriasis questionnaire. The mean (SD) age of the respondents was 47.5 (14.0) years; 27â¯220 (76%) of the respondents were women. Of these 35â¯735 respondents, 3557 (10%) individuals reported having psoriasis. The condition was severe in 878 cases (24.7%), and 299 (8.4%) incident cases were recorded (those arising more than 2 years after participant inclusion in the cohort). After adjustment for confounding factors, a significant inverse relationship was found between the MEDI-LITE score and having severe psoriasis: odds ratio (OR), 0.71; 95% CI, 0.55-0.92 for the MEDI-LITE score's second tertile (score of 8 to 9); and OR, 0.78; 95% CI, 0.59-1.01 for the third tertile (score of 10 to 18). Conclusions and Relevance: Patients with severe psoriasis displayed low levels of adherence to the Mediterranean diet; this finding supports the hypothesis that the Mediterranean diet may slow the progression of psoriasis. If these findings are confirmed, adherence to a Mediterranean diet should be integrated into the routine management of moderate to severe psoriasis.