Guselkumab for hidradenitis suppurativa: a phase II, open-label, mode-of-action study

Abstract

Background Effectiveness of available biologics for the treatment of hidradenitis suppurativa (HS) is limited. Additional therapeutic options are highly needed. Objective To investigate the efficacy and mode of action of guselkumab (an anti-IL-23p19 monoclonal antibody) 200 mg s.c., every four weeks for 16 weeks in HS patients. Methods An open label, multicenter, phase IIa trial in patients with moderate-to-severe HS. The pharmacodynamic response in skin and blood was measured after 16 weeks of treatment. Clinical efficacy was assessed using the HS clinical response (HiSCR), the International Hidradenitis Suppurativa Severity Score System (IHS4), and the abscess and inflammatory nodule (AN) count. Results Thirteen out of 20 patients (65%) achieved HiSCR with also a significant decrease in the median IHS4-score (8.5 to 5.0, p=.002) and the median AN-count (6.5 to 4.0, p=0.002). The overall patient reported outcomes did not show a similar trend. One SAE, likely unrelated to guselkumab treatment was observed. Transcriptomic analysis revealed, in lesional skin, upregulation of various genes associated with inflammation such as immunoglobulin, S100, MMP, keratin, B cell and complement genes, which decreased after treatment in clinical responders. Immunohistochemistry revealed a marked decrease in inflammatory markers in clinical responders at week 16. Conclusions Sixty five (65) percent of moderate-to-severe HS patients achieved HiSCR after 16 weeks of treatment with guselkumab. We could not demonstrate a consistent correlation between gene and protein expression and clinical responses. The main limitations of this study are the small sample size and the absence of a placebo arm. The large placebo-controlled phase IIb NOVA-trial for guselkumab in HS patients, reported a lower HiSCR response of 45.0 to 50.8%, and 38.7% for the placebo group. Guselkumab seems of benefit to only a subgroup of HS patients, indicating that the IL-23/Th17-axis is not central to the pathophysiology of HS.

Emerging Treatments and the Clinical Trial Landscape for Hidradenitis Suppurativa Part I: Topical and Systemic Medical Therapies

“…Of participants receiving guselkumab, 45% and 50.8% met HiSCR at week 16, which was not significantly higher than the placebo group (38.7%). Prior to the phase 2b trial, an open-label phase 2a trial studied guselkumab 200 mg SQ every 4 weeks in 22 patients [ 100 ]. A total of 13 out of 20 (65%) achieved HiSCR, while 7 out of 20 (35%) achieved HiSCR75 at week 16.…”

Long-Term Efficacy of Guselkumab in an Adolescent Hidradenitis Suppurativa Patients: A Case Report

“… 19 , 20 The literature also includes several reports concerning HS, specifically encompassing two recent phase 2 studies and multiple case reports or series. Dudink et al 21 conducted a 24-week open-label, multicenter, phase IIa trial, enrolling 20 patients and divided into 16 weeks of treatment followed by an 8-week follow-up. The primary endpoint was achieving HiSCR at week 16.…”

“…19,20 The literature also includes several reports concerning HS, specifically encompassing two recent phase 2 studies and multiple case reports or series. Dudink et al 21 a follow-up four weeks after treatment cessation. Secondary endpoints involved IHS4 and AN count at these same time points.…”

Adalimumab-Induced Paradoxical Psoriasis Treated with Biologics Targeting the IL-17/IL-23 Axis in Patients with Hidradenitis Suppurativa

“…Moreover, the results from two phase III trials have demonstrated sustained efficacy and safety of secukinumab on HS for up to 52 weeks of treatment, when given every 2 weeks [16]. On the contrary, phase II studies did not provide strong evidence to support the efficacy of IL-23 inhibitors on HS, putting into question the central role of the IL-23/T-helper 17 axis in HS pathophysiology [17, 18].…”