Bimekizumab in the treatment of moderate to severe hidradenitis suppurativa – another approved indication for this biological agent
In May, the primary results of the BE HEARD I and II studies evaluating the efficacy and safety of the IL-17A and IL-17F inhibitor bimekizumab in the treatment of moderate to severe hidradenitis suppurativa (HS) in adults were published in The Lancet. This is the first publication of the results of these Phase III studies. Based on these findings, the European Medicines Agency (EMA) approved bimekizumab (which is currently approved for the treatment of plaque psoriasis, psoriatic arthritis, and axial spondyloarthritis) for the treatment of HS in adults who have not responded adequately to conventional systemic therapy.
Hidradenitis suppurativa – chronic inflammatory skin disease
HS is a chronic recurrent inflammatory skin disease accompanied by comorbidities and significantly reducing the quality of life. It manifests as inflammatory nodules and abscesses with subcutaneous fistulous connections in areas of increased skin friction (especially in the armpits and groin). The abscesses may ooze foul-smelling pus, forming open wounds that heal very slowly and may leave scars. HS affects 0.4–1.0% of the world's population, and 14.5% of those affected are disabled. The disease is associated with an increased incidence of depression and completed suicides, unemployment, and frequent sick leave.
HS is not of infectious origin and is not due to poor hygiene. It is caused by a malfunction of the immune system and is autoimmune in nature. The pathogenesis of HS is complex and involves the actions of IL-17A and IL-17F, which, along with other pro-inflammatory cytokines, induce the influx of neutrophils into skin lesions and maintain chronic inflammation. The only biological treatments approved for HS include the tumor necrosis factor-alpha (TNF-α) inhibitor adalimumab and the IL-17A inhibitor secukinumab. However, nearly half of doctors and patients express dissatisfaction with the current HS treatment options.
Bimekizumab – antibody against IL-17A and IL-17F
Bimekizumab is an IgG1 monoclonal antibody that selectively inhibits both IL-17F and IL-17A. This dual inhibition has shown in vitro effective suppression of pro-inflammatory cytokine production, which was stronger than with the inhibition of IL-17A alone. Bimekizumab has also demonstrated clinically significant benefits in HS patients in a placebo-controlled Phase II study in terms of achieving HiSCR50 (Hidradenitis Suppurativa Clinical Response 50), defined as a ≥ 50% reduction in inflammatory lesions (total abscesses and inflammatory nodules) without an increase in abscesses and draining fistulas.
Methodology and progress of the BE HEARD studies
BE HEARD I and II are 48-week randomized double-blind placebo-controlled multicenter Phase III studies with identical designs. They enrolled patients older than 18 years with moderate to severe HS who were randomized in a 2 : 2 : 2 : 1 ratio to receive bimekizumab 320 mg s.c. every 2 weeks for 48 weeks or 320 mg every 4 weeks for 48 weeks or 320 mg every 2 weeks until the 16th week (then 320 mg every 4 weeks until the 48th week) or placebo until the 16th week (then 320 mg bimekizumab every 2 weeks until the 48th week). The primary outcome was achieving HiSCR50 at week 16.
Results
A total of 505 patients were randomized in the BE HEARD I study and 509 in the BE HEARD II study. HiSCR50 was achieved at week 16 in a significantly greater proportion of patients receiving bimekizumab every 2 weeks than placebo: 48% vs. 29% in the BE HEARD I study (odds ratio [OR] 2.23; 97.5% confidence interval [CI] 1.16–4.31; p = 0.0060) and 52% vs. 32% in the BE HEARD II study (OR 2.29; 97.5% CI 1.22–4.29; p = 0.0032). In the BE HEARD II study, a significantly greater proportion of patients also achieved HiSCR50 with bimekizumab administered every 4 weeks compared to placebo: 54% vs. 32% (OR 2.42; 97.5% CI 1.22–4.80; p = 0.0038). At week 48, the response to treatment persisted or increased.
Serious adverse events during the 48 weeks of bimekizumab treatment were reported in 8% of patients in the BE HEARD I study and 5% in the BE HEARD II study. The most common adverse events, aside from COVID-19 infection, were diarrhea in the BE HEARD I study and oral candidiasis and headache in the BE HEARD II study. One death was reported in the group receiving bimekizumab every 2 weeks due to congestive heart failure in a patient with severe cardiovascular history, which was not linked to the study treatment. No new safety signals related to bimekizumab were identified.
Conclusion
As shown by the recently published results of the BE HEARD I and II studies, bimekizumab is well tolerated in adult patients with moderate to severe HS and leads to a rapid, deep, and clinically significant response to treatment that persisted for the entire 48 weeks of the study. These findings support the use of bimekizumab in this indication and were the basis for its approval in the treatment of moderate to severe HS.
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Sources: Kimball A. B., Jemec G. B. E., Sayed C. J. et al. Efficacy and safety of bimekizumab in patients with moderate-to-severe hidradenitis suppurativa (BE HEARD I and BE HEARD II): two 48-week, randomised, double-blind, placebo-controlled, multicentre phase 3 trials. Lancet 2024; 403 (10443): 2504–2519, doi: 10.1016/S0140-6736(24)00101-6.
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