🔍 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