15716 The high rate of placebo response in hidradenitis suppurativa clinical trials: Recommendations for future clinical trials

Abstract

The authors recently published a systematic review showing a robust placebo response in randomized clinical trials (RCTs) for hidradenitis suppurativa (HS), especially for physical signs. Three additional international/US-based RCTs for moderate-severe HS patients have been reported that did not meet the primary end point and demonstrated high placebo responses (n = 66-179). Four active doses of IFX-1 (IV anti–human complement factor C5a monoclonal antibody; InflaRx) were compared with placebo. IFX-1 treatment achieved a maximum HS Clinical Response (HiSCR) rate of 51.5% while placebo resulted in HiSCR of 47.1%. An RCT investigated MEDI8968 (subcutaneous interleukin-1 receptor 1 inhibitor, AstraZeneca). 23.6% of participants were responders in the active arm (PGA score of 0, 1 or 2 at week 12) compared with 18.5% of those receiving placebo. The study was terminated early. The third RCT compared CJM112 (subcutaneous anti–IL-17A monoclonal antibody; Novartis) versus placebo. Of those receiving active treatment, 32% were responders (decrease in HS-PGA of at least 2 points), while 12.5% of those receiving placebo met this definition. In order to accommodate the large and variable placebo response in HS, the following should be considered: recruit HS patients from well established HS practices, stratify recruitment and randomization across all spectrums of disease activity, employ a trial duration which will account for the natural history of the disease, agree upon a verified set of primary and secondary outcomes; and employ diagnostic imaging techniques to mitigate subjectivity in assessing outcomes. Furthermore, publishing negative outcomes should be encouraged in order to learn from all HS RCTs.