Comparative Efficacy of Hidradenitis Suppurativa Drugs Examined in Absence of Head-to-Head Trials

The efficacy and safety of both approved and investigational drugs for moderate to severe hidradenitis suppurativa offer valuable evidence to guide clinical decision-making in a field where head-to-head trials are largely absent. | Image Credit: JPC-PROD - stock.adobe.com

In a significant step toward improving treatment options for hidradenitis suppurativa, crucial comparative efficacy and safety data for both approved and pipeline medications offer valuable evidence for clinicians and patients in the absence of direct head-to-head clinical trials, according to a study published in JAMA Dermatology.1

Currently, only 3 medications have been approved in the US and Europe to treat hidradenitis suppurativa, marking a significant shift from the past where patients relied mainly on surgery and antibiotics. Adalimumab (Humira; AbbVie) was the first to receive FDA approval in 2015. It wasn't until 2023 that a second drug, secukinumab (Cosentyx; Novartis Pharmaceuticals), was approved, followed a year later by bimekizumab (Bimzelx; UCB) for moderate to severe cases.2

Lutikizumab (ABT-981; AbbVie) and sonelokimab (MoonLake Immunotherapeutics) are 2 potentially new treatments for hidradenitis suppurativa, currently in phase 3 clinical trials.3,4 Neither has received regulatory approval yet, but they represent significant advancements in the drug development pipeline for adult patients with moderate to severe forms of the condition.

This timeline highlights a long period with limited treatment options. However, with 20 phase 2 and 3 clinical trials currently recruiting patients, the future of drug development for this condition looks promising.1

Researchers conducted a network meta-analysis that extracted data, and risk of bias assessments were performed independently by 2 reviewers.1

“The objective of this living systematic review and network meta-analysis was to synthesize and compare efficacy and safety results with the goal of informing treatment guidelines and partnered decision-making on medical management of moderate to severe HS [hidradenitis suppurativa],” study authors stated.1

After screening 26 unique trials, researchers included 25 studies in their analysis, which encompassed 5757 participants, 74 treatment groups, and 39 unique treatments. Placebo was the most frequently studied treatment (n = 25 studies), followed by adalimumab (n = 7), bimekizumab (n = 2 or 3 depending on dose), and secukinumab (n = 2). The median age of participants was 36.9 years, and 63% were women.1

For the Hidradenitis Suppurativa Clinical Response (HiSCR)-50 analysis, 11 of the studies were eligible, including 3384 patients and 17 unique treatments. The most common treatment in this subset was placebo (n = 11), followed by adalimumab (n = 4), bimekizumab (n = 2 or 3 depending on dose), and secukinumab (n = 2). The overall risk of bias was a concern due to high rates of missing data. Among the 11 studies with HiSCR-75 data, 7 were rated as low risk of bias, 3 had some concerns, and 1 was rated as high risk.1

Based on a network meta-analysis, several treatments demonstrated significantly higher odds of achieving a HiSCR-50 response compared with placebo. The most effective of these, ranked by odds ratio, were 120 mg of sonelokimab every 4 weeks (OR, 4.44; 95% CI, 2.29-8.61), 300 mg of lutikizumab every 2 weeks (OR, 2.72; 95% CI, 1.08-6.86), and 40 mg of adalimumab once per week (OR, 2.63; 95% CI, 2.06-3.36).1

While no other treatments showed a significantly greater HiSCR-50 response than adalimumab, adalimumab was found to have similar efficacy to bimekizumab (320 mg every 2 weeks) and was associated with a greater response than secukinumab (300 mg every 4 weeks).1

In the analysis of treatments compared with a placebo, the most significant improvements in the HiSCR-75 response were seen with 120 mg of sonelokimab every 4 weeks (OR, 4.12; 95% CI, 2.00-8.51) and 300 mg of lutikizumab every 2 weeks (OR, 4.01; 95%CI, 1.40-11.47).1

When comparing approved medications, adalimumab demonstrated similar efficacy to bimekizumab. Adalimumab also showed a numerically higher, but not statistically significant, response rate when compared with secukinumab.1

The analysis identified sonelokimab, lutikizumab, bimekizumab, and adalimumab among the top-performing treatments for achieving a HiSCR-75 response, although most differences compared with adalimumab were not statistically significant. In terms of safety, the rates of serious adverse events (AEs) and treatment discontinuations due to AEs were low and comparable across all treatment groups, including placebo, adalimumab, and other therapies.1

For a higher treatment response (HiSCR-75), the study found that sonelokimab, lutikizumab, bimekizumab, and adalimumab were the most effective treatments. However, there were no significant statistical differences between adalimumab and most of the other treatments. Safety data showed that serious adverse events and treatment discontinuation rates were low for all groups, including those on placebo, adalimumab, and other medications.1

The study's findings should be interpreted with caution due to several limitations. The analysis was based on a small, sparsely connected network of only 26 studies, with very few directly comparing different medications. Small sample sizes within treatment groups reduced the precision of the results, and the study could only assess short-term efficacy (12-16 weeks) rather than long-term effects. Therefore, the rankings of treatments are tentative and do not necessarily prove one is superior to another.1

“Phase 2 results for several cytokine and small-molecule treatments are promising and require confirmation in larger phase 3 trials,” study authors concluded.

References

1. Garg A, Cohn E, Midgette B, Frasier K, Strunk A. Efficacy and safety of medical interventions for moderate to severe hidradenitis suppurativa. JAMA Dermatol. 2025. doi:10.1001/jamadermatol.2025.1976
2. Santoro C. Approved hidradenitis suppurativa treatments and pipeline show similar efficacy, safety without head-to-head trials. The American Journal of Managed Care®. July 2, 2025. Accessed August 4, 2025. https://www.ajmc.com/view/approved-hidradenitis-suppurativa-treatments-and-pipeline-show-similar-efficacy-safety-without-head-to-head-trials
3. Andrus E. Lutikizumab demonstrates positive results in phase 2 trial for hidradenitis suppurativa. Dermatology Times®. January 8, 2024. Accessed August 4, 2025. https://www.dermatologytimes.com/view/lutikizumab-demonstrates-positive-results-in-phase-2-trial-for-hidradenitis-suppurativa
4. Bader K. MoonLake’s sonelokimab trial for HS advances to phase 3. Dermatology Times®. May 16, 2024. Accessed August 4, 2025. https://www.dermatologytimes.com/view/moonlake-s-sonelokimab-trial-for-hs-advances-to-phase-3