Can JAK inhibitors effectively treat hidradenitis suppurativa? A promising new approach.

by Haroon Ahmad, MD 2025-03-17 00:00

PhysicianMedical

🔍 Key Finding

Upadacitinib, a selective JAK1 inhibitor, significantly improved hidradenitis suppurativa symptoms compared to placebo, with efficacy maintained through 40 weeks of treatment.

🔬 Methodology Overview

Phase 2, randomized, placebo-controlled, double-blind trial (NCT04430855)
68 adults with moderate-to-severe HS (47 received upadacitinib 30mg; 21 received placebo)
Patients randomized 2:1 to once-daily upadacitinib 30mg or placebo for 12 weeks
At week 12, placebo patients switched to upadacitinib 15mg, while 30mg group continued through week 48
Primary endpoint: ≥50% reduction in total abscess and inflammatory nodule count with no increase in abscess or draining fistula count (HiSCR50) at week 12

📊 Evidence

38.3% of upadacitinib patients achieved HiSCR50 at week 12 vs 25.0% historical placebo rate (difference=13.3%, p=.018)
Compared to in-trial placebo (23.8%), adjusted difference was 14.7% (nominal p=.087)
HiSCR50 response with upadacitinib was consistent across baseline Hurley stages and prior TNFi exposure
Response rates continued to improve through week 40
Among patients with baseline skin pain NRS ≥3, 36.4% achieved NRS30 (≥30% reduction in pain) with upadacitinib vs 22.5% historical placebo

💡 Clinical Impact

This study validates JAK1 as a potential therapeutic target for HS, offering a new mechanism that may more comprehensively address HS pathophysiology by targeting upstream JAK-STAT signaling rather than downstream cytokines. Notably, upadacitinib showed efficacy in patients with inadequate response to TNF inhibitors.

🤔 Limitations

Small sample size (68 patients)
Historical placebo comparison from earlier studies may not reflect current patient populations
Limited data on long-term safety beyond 48 weeks
The waxing and waning nature of HS may contribute to variability in reported outcom

Consider JAK inhibitors as a potential future option for moderate-to-severe HS patients, particularly those who have failed TNF inhibitor therapy. An ongoing phase 3 trial (NCT05889182) is investigating upadacitinib for adults and adolescents with moderate-to-severe HS who have failed anti-TNF therapy, which may provide more definitive evidence for clinical use.

Ackerman LS, Schlosser BJ, Zhan T, Prajapati VH, Fretzin S, Takahashi H, Huang X, Camp HS, Kimball AB. Improvements in moderate-to-severe hidradenitis suppurativa with upadacitinib: Results from a phase 2, randomized, placebo-controlled study. J Am Acad Dermatol. 2025 Feb 25. https://doi.org/10.1016/j.jaad.2024.12.046.