Head-to-head trials of systemic psoriasis therapies: a systematic review of study design and maximum acceptable treatment differences.

There is increasing use of head-to-head clinical trials in dermatology when establishing the efficacy of a new treatment. Active comparator trials (ACTs) can be classified into three distinct study trial designs: non-inferiority, equivalence and superiority. A better understanding of the statistical parameters, such as acceptable treatment differences (also known as the margin or delta), is necessary to properly design and interpret findings of active comparator trials (ACTs) in the field of dermatology. Therefore, the objective of this study was to summarize the maximum acceptable treatment differences in clinical trials that examine the efficacy of an oral or biologic psoriasis therapy with an active comparator. We conducted a systematic search using MEDLINE, Scopus, EMBASE, Cochrane Central Register of Controlled Trials, LILACS, Web of Science and ClinicalTrials.gov from inception to 31 August 2017. All ACTs with adult participants that had a primary outcome of the Psoriasis Area and Severity Index score were included. Bibliographies of articles were further reviewed. Two investigators independently assessed for article inclusion and separately completed data extraction of predefined data points. When there was a disagreement, a third investigator was consulted. Of the 49 ACTs included, there were 13 superiority, eight non-inferiority and seven equivalence trials. Another 21 studies had inadequate information for classification. All of the non-inferiority trials reported the margin, one of the superiority and six of the equivalence trials stated the treatment difference explicitly. For superiority trials, acceptable treatment differences ranged from 14% to 20%. The non-inferiority studies reported lower bound margins ranging from -20% to -10%. The equivalence trials reported upper and lower bound margins ranging from ±12.5% to ±18%. The results demonstrate the need for harmonization in the conduct of dermatological clinical trials and in the approaches of reporting research parameters.

Risk of depression in women with psoriasis: a cohort study.

BACKGROUND: Psoriasis is a common, chronic and inflammatory disease of the skin, which has been associated with depression in cross-sectional studies with limited adjustment for confounders. OBJECTIVES: In this prospective cohort study, we investigated the risk of incident depression among individuals with psoriasis and psoriatic arthritis (PsA). METHODS: We included 50 750 US female nurses from the Nurses' Health Study who were free of depression at baseline in 2000. Those participants who had ever self-reported clinician-diagnosed depression or regular use of antidepressants, or had a Mental Health Inventory score of ≤ 52 were excluded. In 2008, we retrospectively asked participants if they had ever received a physician's diagnosis of psoriasis or PsA. We defined depression as self-report of clinician-diagnosed depression or regular use of antidepressant medication. Time-dependent Cox proportional hazard models were used to estimate age and multivariate-adjusted relative risks (RRs) of clinical depression. RESULTS: After adjusting for covariates including body mass index, physical activity, smoking and the presence of major chronic conditions, the multivariate-adjusted RRs of clinical depression were 1·29 [95% confidence interval (CI) 1·10-1·52] for women with psoriasis and 1·52 (95% CI 1·06-2·19) for women with psoriasis and concomitant PsA, compared with women without psoriasis. CONCLUSIONS: We found an increased risk of depression in US women with psoriasis compared with those without psoriasis. This risk was higher in those who reported concomitant PsA. Future studies are needed to confirm these findings in other populations and to identify pathophysiological mechanisms linking psoriasis to depression.

Reliability, validity and responsiveness to change of the Patient Report of Extent of Psoriasis Involvement (PREPI) for measuring body surface area affected by psoriasis.

BACKGROUND: The development of a simple, reliable, valid and responsive method for measuring the extent of skin involvement in psoriasis is important for use in epidemiological studies. OBJECTIVES: We sought to investigate the psychometric characteristics of the Patient Report of Extent of Psoriasis Involvement (PREPI), a single-question method for measuring body surface area affected by psoriasis. METHODS: This was a cross-sectional study of 140 patients with psoriasis, with an exploratory prospective longitudinal cohort component. Reliability was measured via a test-retest approach and criterion validity was investigated by comparing the PREPI with an assessment of body surface area of involvement by a dermatologist. We additionally compared Skindex-29 scores with the PREPI. To demonstrate responsiveness and establish a minimally important difference in the PREPI, we created receiver operating characteristic curves for the PREPI instrument. RESULTS: The test-retest reliability of the PREPI was nearly perfect [intraclass correlation coefficient (ICC) = 0.99, 95% confidence interval (CI) 0.97-0.99], and there was substantial agreement between patient and physician assessments (ICC = 0.82, 95% CI 0.75-0.87). The PREPI showed significant correlations with all Skindex-29 domains. We found the PREPI to be responsive to change and identified changes in the PREPI score that have good discrimination between patients with and without a minimally important clinical difference. CONCLUSIONS: Our study suggests that the PREPI is a reliable, valid and responsive measure of body surface area affected by psoriasis that may be useful for future epidemiological research.