Review Highlights Most Effective HS Therapies Based on HiSCR-50 Responses

The highest ranking hidradenitis suppurativa (HS) therapies based on Hidradenitis Suppurativa Clinical Response (HiSCR)-50 response are adalimumab, sonelokimab, lutikizumab, sonelokimab, and bimekizumab, according to recent findings.1

The systematic review that led to this conclusion specifically identified these treatments by HiSCR-50 response in the following dosages: adalimumab, 40 mg, once-weekly; sonelokimab, 120 mg, every 4 weeks; lutikizumab, 300 mg, every 2 weeks; sonelokimab, 240 mg, every 4 weeks; and bimekizumab, 320 mg, every 2 weeks.

This systematic review and network meta-analysis was published in JAMA and authored by such investigators as Amit Garg, MD, from the Zucker School of Medicine at Hofstra/Northwell Department of Dermatology in New York. Garg et al highlighted the robust treatment pipeline for HS therapies.2

“The objective of this living systematic review (LSR) 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,” Garg and coauthors wrote.1

Design and Notable Findings

The investigative team considered randomized controlled trials (RCTs) with a parallel-group design that assessed pharmacologic drugs for adults with moderate-to-severe HS to be eligible for inclusion in their review and meta-analysis. Interventions Garg and coauthors deemed eligible included cytokine blockers, cellular inhibitors, small molecule agents, and other innovative treatments designed to impact immune or inflammatory pathways among those with HS.

Research that would qualify for the investigators' analysis was also required to report on at least a single measure of safety, efficacy, or therapy tolerability. In order to be included in the meta-analysis, efficacy outcomes in the RCTs analyzed needed to be assessed between 12 - 16 weeks following initiation of the drug being evaluated.

The investigative team carried out their search across 2 databases—Medline and Embase—as well as 2 clinical trial registries—ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials (CENTRAL)—from their inception through June 2024. The team also implemented manual reviews of reference lists from eligible research as well as prior systematic reviews on HS therapies. Independent title/abstract and full-text screenings were done by 2 coauthors, along with standardized data extraction.

HiSCR-50, or attainment of 50% inflammatory nodule and abscess reduction, serious adverse event (SAE) incidence, and drug discontinuation resulting from AEs were the main endpoints evaluated by Garg et al. Despite the fact that HiSCR-50 was the investigators' main measure of treatment efficacy, results for HiSCR-75 were also reported.

Risk of bias (RoB) in included RCTs was independently assessed by a pair of reviewers via the Cochrane RoB-2 tool. Any notable discrepancies were then resolved through discussion. They based RoB judgments on the HiSCR-50 outcome.

Among 26 eligible analyses, Garg and coauthors found that 25 included data on HiSCR-50. These studies would encompass a total of 5,767 individuals and assess 39 distinct therapeutic agents. Overall, the investigators found that several of these agents demonstrated significantly greater HiSCR-50 response rates than those of placebo, including:

• Sonelokimab 120 mg every 4 weeks
• Adalimumab 40 mg weekly
• Lutikizumab 300 mg every 2 weeks
• Sonelokimab 240 mg every 2 weeks
• Bimekizumab 320 mg every 2 weeks
• Bimekizumab 320 mg every 4 weeks
• Povorcitinib 15 mg daily
• Secukinumab 300 mg every 2 weeks
• Secukinumab 300 mg every 4 weeks

Most head-to-head comparisons that had been made between adalimumab 40 mg each week and other targeted agents did not demonstrate statistically significant differences in rates of patient response.

The incidence of SAEs was shown by the investigative team to range from 0% - 10% in the placebo arms, 0% - 8% in those treated with adalimumab (40 mg weekly), and 0% - 6% among other active therapies. AE-related discontinuation was noted by the team as varying from 0% - 10% in placebo cohorts, 0% - 4% for adalimumab-treated individuals, and up to 15% for subjects given other active agents. The team highlighted that the highest rate was observed in the ropsacitinib group.

“This [living systematic review] and [network meta-analysis] provides evidence for the comparative efficacy and safety of currently approved cytokine inhibitors for moderate to severe HS in the absence of head-to-head trials,” the investigators wrote.1 “Phase 2 results for several cytokine and small-molecule treatments are promising and require confirmation in larger phase 3 trials.”

References

1. Garg A, Cohn E, Midgette B, Frasier K, Strunk A. Efficacy and Safety of Medical Interventions for Moderate to Severe Hidradenitis Suppurativa: A Living Systematic Review and Network Meta-Analysis. JAMA Dermatol. Published online July 02, 2025. doi:10.1001/jamadermatol.2025.1976.

2. U.S. National Library of Medicine. ClinicalTrials.gov. Updated April 14, 2025. Accessed May 5, 2025. https://clinicaltrials.gov/search?cond=hidradenitis%20suppurativa&aggFilters=phase:2%203,status:rec,studyType:int.