Users of biologics in clinical practice: would they be eligible for phase III clinical studies? Cohort Study in the French Psoriasis Registry PSOBIOTEQ

Abstract

Background: Numerous inclusion and exclusion criteria are involved in phase III moderate to severe psoriasis trials investigating the safety and efficacy of biologics. This questions the generalization of results. Methods: In this cohort study, we applied inclusion/exclusion criteria for phase III trials from original protocols (adalimumab – REVEAL, ustekinumab – PHOENIX, brodalumab – AMAGINE, secukinumab FIXTURE) to all patients enrolled in the PsoBioTeq prospective registry who received a biological agent for the first time between July 2012 and November 2017. We then compared the efficacy, drug survival and occurrence of adverse events between patients who satisfied/did not satisfy the eligibility criteria for these phase III trials. Results: A total of 1267 patients were enrolled, of whom 993 (78.4%) were not eligible for at least one RCT (randomized controlled trial) and 251 (19.1%) did not meet the PASI/PGA severity requirements. Apart from disease severity, the most frequent criteria resulting in exclusion were as follows: non-plaque psoriasis (12.6%), significant cardiac disease (8.4%), significant liver disease (7.3%), elevated liver enzymes (4.9–9.6%) and personal history of diabetes (9.2%). There was no difference in drug survival between the two groups. The incidence ratio of adverse events was significantly lower in eligible versus non-eligible patients [0.78 (95% CI 0.62–0.97) (P = 0.03)]. Conclusion: The majority of patients treated with biologics in the PsoBioTeq real-life registry would not have been eligible for phase III moderate to severe psoriasis trials. Patients not eligible for psoriasis phase III clinical trials have a higher incidence of adverse events.