Emerging JAK1 and C5a Inhibitors Show Promise in Hidradenitis Suppurativa Network Meta-Analysis
A systematic review and network meta-analysis suggests that emerging targeted therapies—particularly JAK1 and C5a inhibitors—may offer improved efficacy and tolerability for patients with moderate-to-severe hidradenitis suppurativa (HS), a population with substantial unmet treatment needs.
“Despite current treatments, approximately 50% of patients remain refractory at 12 to 16 weeks,” the investigators noted, emphasizing the limitations of existing therapies such as TNF-α and IL-17 inhibitors. This study aimed to evaluate investigational biologics and small-molecule therapies relative to approved treatments.
Following PRISMA guidelines, databases, including Embase, Medline, PubMed, and ClinicalTrials.gov, were searched for phase II to IV randomized controlled trials evaluating systemic immunomodulatory therapies in adults with moderate-to-severe HS. A total of 31 studies (n=6129) were included, with efficacy assessed by Hidradenitis Suppurativa Clinical Response 50 (HiSCR50) at 12 to 16 weeks and safety evaluated by adverse event rates.
Several investigational therapies demonstrated improved efficacy compared with approved treatments. Brepocitinib (OR 1.30; 95% CI, 1.04–1.62) and porvocitinib (OR 1.37; 95% CI, 1.10–1.71) showed superior HiSCR50 response rates compared with secukinumab. In terms of safety, upadacitinib (OR 0.43; 95% CI, 0.33–0.57) and vilobelimab (OR 0.76; 95% CI, 0.59–0.97) demonstrated better tolerability compared with adalimumab, with fewer adverse events.
These findings suggest a potential shift in the treatment landscape, particularly for patients who do not respond to current biologics.
“JAK1 (porvocitinib, brepocitinib, and upadacitinib) and C5a (vilobelimab) inhibitors…offer promising potential future treatment alternatives for patients refractory to or intolerant of current therapies,” the authors concluded.
“However, the small-to-moderate sample sizes and short-term follow up… highlight the need for future larger, longer-term trials,” the authors added.
These results underscore the evolving therapeutic pipeline in HS and the importance of continued clinical investigation to validate these early signals.
Reference
Simpson RS, Cirone K, Akrout M, et al. Comparative efficacy and safety of novel biologics and small-molecule therapies for moderate-to-severe hidradenitis suppurativa: a systematic review and network meta-analysis. Presented at: American Academy of Dermatology Annual Meeting; March 27–31, 2026; Denver, Colorado.
