番茄社区

More than twice as many patients with moderate or severe hidradenitis suppurativa (HS) responded to the interleukin (IL)-17 inhibitor bimekizumab versus placebo, a preliminary trial showed.

After 12 weeks of treatment, 57.3% of patients treated with bimekizumab had at least a 50% improvement in baseline lesions compared with 26.1% of patients randomized to placebo.

Additionally, 46% of bimekizumab patients had at least a 75% improvement from baseline and 32% had at least a 90% improvement versus 10% and 0% for placebo, respectively, reported Gregor Jemec, MD, of Zealand University Hospital in Roskilde, Denmark, and co-authors.

Among patients in an adalimumab (Humira) reference group, 35% had at least a 75% improvement from baseline and 15% had a 90% or greater improvement, they noted in .

Serious adverse events occurred infrequently in all three treatment groups.

"These data suggest that dual inhibition of IL-17A and IL-17F by bimekizumab may be a viable treatment approach for HS, with the potential to achieve deep responses in clinical outcomes," Jemec and colleagues concluded. "Although data are encouraging, the sample size was limited, and longer studies are needed to understand response durability. Further dose regimen elucidation is required because only a single dose regimen was studied. The inflammatory burden of the disease and current pharmacologic treatment outcomes suggest an intensive dosing regimen ... may be needed for optimal treatment."

"The efficacy and safety findings in this study warrant confirmation with large phase III studies," they added.

Patients with moderate or severe HS have few effective treatment options beyond surgery. No new HS-specific drugs have become available since 2015, when the FDA made adalimumab the first approved therapy for HS.

IL-17A and IL-17F are recognized drivers of chronic joint and skin inflammation, and inhibitors of IL-17A have demonstrated efficacy in the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis, the authors noted. However, benefits with inhibition of IL-17A alone are inadequate or nonexistent for many patients.

"We hypothesize that dual-cytokine blockade may profoundly affect chronic tissue inflammation," they wrote. "Blocking both cytokines may confer additional efficacy in immune-mediated diseases, such as HS, in which IL-17-producing T_H cells infiltrate the lesional dermis."

Trial Design and Findings

Jemec and co-authors reported findings from an international, phase II, randomized (2:1:1) trial that compared bimekizumab and placebo, with an adalimumab reference arm, in patients with moderate or severe HS. The primary efficacy endpoint was Hidradenitis Suppurative Clinical Response (HiSCR), defined as at least a 50% reduction in total abscess and nodule count with no increase in abscess or draining fistula count at 12 weeks, in the bimekizumab and placebo groups. The proportion of patients achieving a 75% and 90% improvement from baseline (HiSCR₇₅, HiSCR₉₀) were exploratory endpoints.

Investigators employed Bayesian analysis to incorporate historical data to increase the power to detect meaningful differences between groups with smaller numbers of patients.

Data analysis included 88 randomized patients. The patients had a median age of 36, and women accounted for 69% of the study population. Baseline characteristics were similar among treatment groups, with the exception of C-reactive protein levels and quality-of-life scores, which were numerically higher in the adalimumab arm.

The primary analysis showed that 25 of 40 patients in the bimekizumab arm met criteria for clinical response as compared with five of 18 in the placebo group. The posterior probability of superiority for bimekizumab was 0.998. In the adalimumab arm, 12 of 18 evaluable patients achieved clinical response.

The exploratory analysis showed HiSCR₇₅ responses in 20 of 40 patients in the bimekizumab arm, two of 18 in the placebo group, and seven of 18 in the adalimumab arm. HiSCR₉₀ responses occurred in 14 of 40 patients in the bimekizumab arm, none of the placebo-treated patients, and three of 18 patients in the adalimumab arm. Modeled posterior probability of superiority analyses showed that bimekizumab met superiority criteria versus placebo.

Data from the Patient Global Assessment of Pain showed that 27 of 42 evaluable patients in the bimekizumab arm had at least a 30% improvement and at least a 1-point reduction in score at 12 weeks, as compared with seven of 19 in the placebo group and nine of 18 in the adalimumab group. The proportion of patients who achieved a Dermatology Life Quality Index score of 0/1 (remission) was 36% with bimekizumab, 0% with placebo, and 14% with adalimumab. Bimekizumab and adalimumab achieved similar response rates on the International Hidradenitis Suppurativa Severity Score and both were more than 50% better than placebo.

Key Takeaway

"The key takeaway is that bimekizumab showed clear efficacy over placebo for all important study endpoints, including the primary endpoint of HiSCR response that is used in most clinical trials examining treatment of HS," co-author Christopher Sayed, MD, of the University of North Carolina at Chapel Hill, told 番茄社区 via email. "It was well tolerated overall with a side effect profile similar to placebo and adalimumab, including oral candidiasis, which was seen at higher rates in recent psoriasis trials."

The study was notable for its analyses of HiSCR₇₅ and HiSCR₉₀, which were not incorporated into the pivotal trials of adalimumab.

"HiSCR₇₅ and HiSCR₉₀ are much more difficult to achieve clinically," Sayed said. "Placebo response rates for these measures were also much lower than what is typically seen for the standard HiSCR₅₀, and there was clear superiority of bimekizumab compared to placebo. One of the biggest challenges with current treatments is that patients partially respond, but still carry a high burden of disease. These deeper responses will be much more clinically meaningful for patients."

Comment