Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients

A systematic review of the use of quality-of-life instruments in randomized controlled trials for psoriasis

This is the peer reviewed version of the following article: F. M. Ali, A. C. Cueva, J. Vyas, A. A. Atwan, M. S. Salek, A. Y. Finlay, and V. Piguet, ‘A systematic review of the use of quality-of-life instruments in randomized controlled trials for psoriasis’, British Journal of Dermatology, Vol. 176 (3): 577-593, March 2017, which has been published in final form at https://doi.org/10.1111/bjd.14788. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Planners of interventional studies in psoriasis face the dilemma of selecting suitable quality-of-life (QoL) measures. Systematic reviews have the potential of identifying psychometrically sound measures in a given therapeutic area, while guiding the development of practice guidelines. The aim of this systematic review was to generate evidence of the use of QoL instruments in randomized controlled trials (RCTs) for interventions in psoriasis. The methodology followed the PRISMA guidelines. Six databases were searched with 388 search terms. Abstracts of articles were reviewed independently by two assessors, and a third adjudicator resolved any opinion differences. Risk of bias was assessed using the Jadad scale. Of 3646 screened publications, 99 articles (100 trials) met the eligibility criteria for inclusion, describing research on 33 215 patients. Thirty-three trials tested topical therapy, 18 systemic, 39 biologics, nine phototherapy and 10 other interventions. The Dermatology Life Quality Index (DLQI) was the most commonly used QoL instrument (83 studies, 83%), followed by the 36-Item Short Form Survey (SF-36) (31, 31%), EuroQoL-5D (EQ-5D) (15, 15%), Psoriasis Disability Index (14, 14%) and Skindex (five, 5%). There was widespread inconsistency in the way that QoL data were reported. Of the 100 trials identified, 37 reported minimal clinically important difference (MCID): 32 for DLQI, 10 for SF-36 and six for EQ-5D. QoL measurement is increasingly being reported in RCTs of psoriasis. Formal guidelines are needed for assessment and publishing of QoL data. Researchers should consider whether MCID information is available, and development of MCID data should be encouraged.Peer reviewedFinal Accepted Versio

Avaliação dos efeitos adversos clínicos e alterações laboratoriais em pacientes com acne vulgar tratados com isotretinoína oral Evaluation of clinical adverse effects and laboratory alterations in patients with acne vulgaris treated with oral isotretinoin

FUNDAMENTOS: A isotretinoína oral revolucionou o manejo da acne. Os efeitos adversos observados, durante o tratamento, são divididos em dois grupos: mucocutâneos e sistêmicos. Anormalidades laboratoriais, principalmente, as dislipidemias e aumento das enzimas hepáticas são relatados. OBJETIVO: Avaliar a tolerabilidade da isotretinoína oral, com atenção, no metabolismo lipídico, função hepática e reações adversas clínicas. MÉTODOS: Foram incluídos 150 pacientes com diagnóstico clínico de acne submetidos a tratamento com isotretinoína oral. Avaliações clínicas e laboratoriais foram feitas, após um mês e a cada três meses, até completar o tratamento. RESULTADOS: Dos 150 pacientes 48% eram do sexo feminino e 52% do sexo masculino. A idade variou de 15 a 32 anos. Quanto aos efeitos adversos cutâneos e mucosos da isotretinoína, queilite foi o mais frequente, ocorrendo em 94% pacientes. Efeitos clínicos sistêmicos foram bem menos comuns. Os níveis de colesterol, triglicerídeos, transaminases, foram avaliados e não mostraram alterações significativas, ao longo do tratamento. CONCLUSÃO: Os pacientes apresentaram efeitos adversos, compatíveis com os da literatura, e, em sua maioria, controlados com medicações sintomáticas. Podemos concluir que a isotretinoína é uma droga segura, em relação a seus efeitos adversos, tanto clínicos como laboratoriais.<br>BACKGROUND: Oral isotretinoin therapy has completely changed the treatment of acne. The clinical adverse effects of isotretinoin are classified into two groups: mucocutaneous and systemic toxic. Laboratory alterations such as dyslipidemia and increase of hepatic enzymes are reported. OBJECTIVES: To evaluate the tolerability of oral isotretinoin with special attention to lipid metabolism, hepatic function, and clinical adverse reactions. METHODS: 150 patients clinically diagnosed with acne being treated with oral isotretinoin were included in the study. Clinical and laboratory evaluations were conducted before the start of therapy, one month after, and every three months thereafter until the completion of treatment. RESULTS: Of the 150 patients evaluated, 48% were female and 52%, male. They were aged from 15 to 32 years. The most prevalent mucocutaneous adverse reaction associated with isotretinoin therapy was cheilitis, reported by 94% of the patients. Systemic clinical effects were much less common. Cholesterol, triglyceride, and transaminase levels were assessed and significant changes were not observed during treatment. CONCLUSION: Patients showed adverse effects compatible to those described in the literature, which are mostly controlled with symptomatic medication. Isotretinoin is a safe drug and adverse and laboratory effects are well tolerated