Efficacy and Safety of Bimekizumab in Moderate to Severe Hidradenitis Suppurativa: A Phase 2, Double-blind, Placebo-Controlled Randomized Clinical Trial

Abstract

Importance: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a high burden for patients and limited existing therapeutic options.

Objective: To evaluate the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin 17A and 17F in individuals with moderate to severe HS.

Design, setting, and participants: This phase 2, double-blind, placebo-controlled randomized clinical trial with an active reference arm was performed from September 22, 2017, to February 21, 2019. The study included a 2- to 4-week screening period, a 12-week treatment period, and a 20-week safety follow-up. Of 167 participants screened at multiple centers, 90 were enrolled. Eligible participants were 18 to 70 years of age with a diagnosis of moderate to severe HS 12 months or more before baseline.

Interventions: Participants with HS were randomized 2:1:1 to receive bimekizumab (640 mg at week 0, 320 mg every 2 weeks), placebo, or reference arm adalimumab (160 mg at week 0, 80 mg at week 2, and 40 mg every week for weeks 4-10).

Main outcomes and measures: The prespecified primary efficacy variable was the proportion of participants with a 50% or greater reduction from baseline in the total abscess and inflammatory nodule count with no increase in abscess or draining fistula count (Hidradenitis Suppurativa Clinical Response [HiSCR] at week 12. Exploratory variables included proportion achieving a modified HiSCR with 75% reduction of HiSCR criteria (HiSCR75) or a modified HiSCR with 90% reduction of HiSCR criteria (HiSCR90), change in Patient's Global Assessment of Pain, and Dermatology Life Quality Index total scores.

Results: Eighty-eight participants received at least 1 dose of study medication (61 [69%] female; median age, 36 years; range, 18-69 years). Seventy-three participants completed the study, including safety follow-up. Bimekizumab demonstrated a higher HiSCR rate vs placebo at week 12 (57.3% vs 26.1%; posterior probability of superiority equaled 0.998, calculated using bayesian analysis). Bimekizumab demonstrated greater clinical improvements compared with placebo. Improvements in the International Hidradenitis Suppurativa Severity Score (IHS4) were seen at week 12 with bimekizumab (mean [SD] IHS4, 16.0 [18.0]) compared with placebo (mean [SD] IHS4, 40.2 [32.6]). More bimekizumab-treated participants achieved positive results on stringent outcome measures compared with placebo. At week 12, 46% of bimekizumab-treated participants achieved HiSCR75 and 32% achieved HiSCR90, whereas 10% of placebo-treated participants achieved HiSCR75 and none achieved HiSCR90; in adalimumab-treated participants, 35% achieved HiSCR75 and 15% achieved HiSCR90. One participant withdrew because of adverse events. Serious adverse events occurred in 2 of 46 bimekizumab-treated participants (4%), 2 of 21 placebo-treated participants (10%), and 1 of 21 adalimumab-treated participants (5%).

Conclusions and relevance: In this phase 2 randomized clinical trial, bimekizumab demonstrated clinically meaningful improvements across all outcome measures, including stringent outcomes. Bimekizumab's safety profile was consistent with studies of other indications, supporting further evaluation in participants with HS.

Trial registration: ClinicalTrials.gov Identifier: NCT03248531.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Glatt reported receiving personal fees as an employee of UCB Pharma during the conduct of the study and outside the submitted work. Dr Jemec reported receiving grants from AbbVie, LEO Foundation, Afyx, InflaRx, Janssen-Cilag, Novartis, UCB, CSL Behring, Regeneron, Sanofi, Boehringer Ingelheim, Union Therapeutics, and Toosonix and personal fees from Coloplast, Chemocentryx, LEO Pharma, Incyte, Kymera, and VielaBio during the conduct of the study; in addition, Dr Jemec had a patent for hidradenitis suppurativa prevention issued. Dr Forman reported receiving personal fees from ForSight Consulting outside the submitted work. Dr Sayed reported receiving grants from UCB during the conduct of the study and grants from AbbVie, Novartis, Incyte, Chemocentryx, and InflaRx and personal fees from AbbVie and Novartis outside the submitted work. Dr Weisman reported receiving personal fees and grants from UCB during the conduct of the study and grants from Janssen, Pfizer, AbbVie, Eli Lilly, Boehringer Ingelheim, Bristol-Myers Squibb, Avillion, Sun, Amgen, and Novartis and personal fees from Janssen, Novartis, Bristol-Myers Squibb, and Eli Lilly outside the submitted work. Drs Rolleri, Baeten, Ionescu, and Shaw reported being employees of UCB Pharma. Dr Zouboulis reported being paid by AbbVie, InflaRx, Novartis, and UCB Pharma for participation in clinical studies and personal fees from AbbVie, Idorsia, Incyte, InflaRx, Janssen, Novartis, Regeneron, and UCB Pharma outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Study Design, Disposition, and Discontinuation

aRandomization was stratified according to Hurley stage at baseline (II or III). bBimekizumab-treated participants received a loading dose of 640 mg at baseline and then 320 mg every other week from week 2, with a final dose at week 10. cPlacebo was given at baseline, week 2, and then every week from week 4 to maintain the blinding. dAdalimumab-treated participants received a loading dose of 160 mg at baseline, 80 mg at week 2, and then 40 mg every week from week 4, with a final dose at week 10. Because of differences in dosing schedule between bimekizumab and adalimumab, placebo injections were administered along with active treatment such that all participants received the same number of injections at each visit. Owing to differences in presentation between bimekizumab and adalimumab, unblinded study personnel prepared and administered the study medication to maintain the blind. The unblinded study personnel did not have any other involvement in the study.

Figure 2.. Primary Analysis

Bayesian analysis was performed in which the posterior probability distribution for the difference in the primary end point (Hidradenitis Suppurativa Clinical Response [HiSCR] at 12 weeks) between bimekizumab-treated and placebo-treated participants confirmed that the superiority criteria for bimekizumab were met. NRI indicates nonresponder imputation.

Figure 3.. International Hidradenitis Suppurativa Severity Score (IHS4), Patient’s Global Assessment of Pain (PtGA), and Dermatology Life Quality Index (DLQI) Scores in the Full Analysis Set (Observed Data)

aIHS4 = (number of inflammatory nodules ×1) + (number of abscesses ×2) + (number of draining fistulae ×4). bMean PtGA of skin pain judged as pain at its worst in the last 24 hours (before week 12 visit) using an 11-point numeric rating scale.