A living network meta-analysis evaluated the efficacy and safety of 39 drug regimens using data from 25 randomized clinical trials involving 5,767 participants with moderate to severe hidradenitis suppurativa. The analysis assessed each treatment's ability to achieve a 50% reduction in abscess and inflammatory nodule count without worsening of abscesses or draining fistulas, a measure known as the Hidradenitis Suppurativa Clinical Response. It also evaluated HiSCR-75 outcomes, serious adverse events, and treatment discontinuation due to adverse events.
Nine treatments demonstrated significantly higher HiSCR-50 response rates compared with placebo. The highest response rates were observed with sonelokimab 120 mg every 4 weeks (odds ratio [OR], 4.44; 95% CI, 2.29-8.61), corresponding to a 35.6% absolute difference versus placebo. This was followed by lutikizumab 300 mg every 2 weeks (OR, 2.72; 95% CI, 1.08-6.86; 24.2% absolute difference) and adalimumab 40 mg once per week (OR, 2.63; 95% CI, 2.06-3.36; 23.4% absolute difference).
Based on treatment rankings, the top five treatments for HiSCR-50 were: sonelokimab 120 mg every 4 weeks, adalimumab 40 mg once per week, sonelokimab 240 mg every 4 weeks, lutikizumab 300 mg every 2 weeks, and bimekizumab 320 mg every 2 weeks. Additional agents with significant HiSCR-50 benefit included povorcitinib and secukinumab.
HiSCR-75 outcomes were available from 11 trials involving 3,384 participants. Sonelokimab 120 mg every 4 weeks again demonstrated the highest OR (4.12; 95% CI, 2.00-8.51; 28.5% absolute difference), followed by lutikizumab 300 mg every 2 weeks (OR, 4.01; 95% CI, 1.40-11.47; 27.8% absolute difference), bimekizumab, and adalimumab.
Adalimumab, one of the few agents with regulatory approval for hidradenitis suppurativa in the U.S. and Europe, was the most studied treatment. Importantly, most differences between adalimumab and other targeted treatments were not statistically significant. Although point estimates for HiSCR-50 and HiSCR-75 occasionally favored newer agents such as sonelokimab and lutikizumab, no treatment demonstrated statistically significant superiority over adalimumab.
The strong effect sizes observed for sonelokimab and lutikizumab should be interpreted with consideration of their smaller sample sizes in phase 2 trials, which contribute to greater uncertainty as reflected in wide confidence intervals.
Across trials, serious adverse events occurred in up to 10% of placebo patients, up to 8% of those receiving adalimumab, and up to 6% in most other active treatment groups. Discontinuation due to adverse events was generally low but reached 15% in one trial of ropsacitinib. Discontinuation rates were also numerically higher with bimekizumab and zimlovisertib, though estimates were imprecise and confidence intervals were wide.
The majority of treatment comparisons were indirect due to a limited number of head-to-head trials. Small sample sizes and short follow-up durations (12–16 weeks) contributed to imprecision in some estimates and limited overall confidence in treatment effects. Nevertheless, the analysis offers comparative insights into short-term efficacy and tolerability of currently available and investigational treatments for hidradenitis suppurativa. Larger, longer-term randomized clinical trials are needed to confirm these findings and guide clinical decision-making.
Full disclosures are available in the published article.
Source: JAMA Dermatology