Bimekizumab shows promise for hidradenitis suppurativa

The monoclonal IgG1 antibody bimekizumab, which selectively inhibits both interleukin(IL)-17A and 17F, demonstrated clinically meaningful improvements for moderate-to-severe hidradenitis suppurativa (HS) or acne inversa, a phase II study suggests.

“[Our] initial clinical efficacy and safety data suggest that dual inhibition of IL-17A and 17F by bimekizumab may be a viable treatment approach for HS, with the potential to achieve deep responses in clinical outcome measures, and support further evaluation,” said the researchers.

A chronic inflammatory disease, HS manifests as painful, deep-seated lesions in sensitive body areas*, which may rupture and form sinus tracts that may eventually warrant surgical removal. [N Engl J Med 2012;366:158-164; J Eur Acad Dermatol Venereol 2015;29:619-644] “[The] extensive scarring and fibrosis can lead to contractures and limb mobility limitations. Because of the pain, sensitive location, and malodorous discharge, patients’ quality of life (QoL) is negatively affected, and considerable psychological distress occurs,” they explained.

Moreover, limited therapeutic options exist for moderate-to-severe HS, with adalimumab being the only currently approved biologic therapy. [Expert Rev Clin Immunol 2016;12:1015-1026]

Ninety participants (median age 36 years, 69 percent female) were randomized 2:1:1 to receive bimekizumab 320 mg Q2W (after a 640-mg loading dose at baseline), placebo, or adalimumab 40 mg weekly from week 4 (after a 160-mg loading dose at baseline and 80 mg at week 2). [JAMA Dermatol 2021;doi:10.1001/jamadermatol.2021.2905]

Week 12 saw greater improvements with bimekizumab vs placebo in terms of HiSCR** rate (mean, 57 percent vs 26 percent; posterior probability of superiority=0.998) and IHS4*** (mean, 16.0 vs 40.2). A non-Bayesian sensitivity analysis indicated superiority of bimekizumab over placebo in terms of HiSCR response (odds ratio, 3.95).

Using more stringent outcomes that have not been evaluated in previous studies, nearly half of bimekizumab recipients were HiSCR₇₅** responders as opposed to placebo (46 percent vs 10 percent), while a third were HiSCR₉₀** responders (32 percent vs 0 percent). “[These] provide preliminary evidence that bimekizumab has the potential for greater lesion clearance and thereby benefit to participants.”

Week 12 also saw more bimekizumab vs placebo recipients experiencing remission (DLQI^# 0/1, 36 percent vs 0 percent), with greater improvements in skin pain (≥30 percent and ≥1-unit reduction, 64 percent vs 37 percent).

Those on adalimumab exhibited either similar or smaller improvements vs those on bimekizumab in terms of improvements in IHS4 (16.5), as well as proportions of case responders with improvements in skin pain (50 percent) and those achieving DLQI 0/1 (14 percent), HiSCR75 (35 percent), and HiSCR90 (15 percent).

There were similar treatment-emergent adverse event (TEAE) rates across the bimekizumab, placebo, and adalimumab arms (70, 62, and 71 percent, respectively), with most being mild or moderate. Only two serious AEs occurred with bimekizumab, and one case of study withdrawal owing to a TEAE (worsening HS). The most frequent TEAEs with bimekizumab use were infections/infestations (44 percent), skin/subcutaneous tissue disorders (28 percent), and general disorders/administration site conditions (22 percent).

“Overall, there were no unexpected safety findings. The initial safety profile in HS was consistent with bimekizumab trials for other indications under development,” said the researchers.

Why dual inhibition?

Not all patients with rheumatologic conditions^## respond to anti-IL-17A inhibitors despite their reported efficacy. [Curr Rheumatol Rep 2015;17:55; Arthritis Res Ther 2017;19:51] “IL-17A and IL-17F have been identified as drivers of chronic joint and skin inflammation, share approximately half their structural homology, and have overlapping pro-inflammatory functions,” the researchers said.

“We hypothesized that dual-cytokine blockade may profoundly affect chronic tissue inflammation. Blocking both cytokines may confer additional efficacy in immune-mediated diseases … [As such,] dual inhibition of IL-17A and IL-17F [may be] a potential treatment opportunity,” they continued.

Bimekizumab’s novel mechanism of action has been seen in several studies on psoriasis and psoriatic arthritis, thereby supporting the theory that inhibition of both IL-17A and IL-17F can lead to deep responses. [Lancet 2020;395:427-440; N Engl J Med 2021;385:142-152; N Engl J Med 2021;385:130-141; Lancet 2021;397:475-486; Lancet 2021;397:487-498] The researchers called for longer and larger phase III studies to further ascertain the efficacy and safety of bimekizumab, as well as dosing and durability of the responses for HS patients.