Hidradenitis suppurativa: TYK2/JAK1 inhibitor shows promise

Out of 3 parallel tested kinase inhibitors, only brepocitinib met its primary efficacy endpoint of the Hidradenitis Suppurativa Clinical Response (HiSCR) score in a phase 2b study. The TYK2/JAK1 inhibitor also significantly reduced hidradenitis suppurativa (HS) flares.

“We will look back on this meeting as an important milestone in our understanding of both the treatment and pathophysiology of HS,” Prof. Alexandra Kimball (Harvard Medical School, MA, USA) opened her talk on an umbrella study in HS [1]. This study design, novel to dermatology, was used to investigate 3 experimental agents with different modes of action versus placebo in a phase 2b trial (NCT04092452) on patients with moderate-to-severe HS, i.e. Hurley stages 2 and 3. A total of 194 participants were included in the different treatment and placebo groups of this umbrella study. “This design allows you to pool the placebo groups to evaluate against all the different measures at the end,” Prof. Kimball explained. The active study drugs included the IRAK4 inhibitor PF-06650833 (400 mg/day), the TYK2 inhibitor PF-06826647 (400 mg/day), and the TYK2/JAK1 inhibitor brepocitinib (45 mg/day). The primary endpoint consisted of the percentage reaching HiSCR at week 16, which stands for a 50% reduction in abscesses and inflammatory nodules compared with baseline.

The mean participant age in the various groups ranged from 37‒40 years, BMI from 35.12 to 36.64, and 72.3‒87.5% were women. Within the ethnically diverse population, 61.5‒72.3% had Hurley stage 2, 20.8‒23.4% were previous inadequate responders to anti-TNF, and 10.6‒14.6% concomitantly used antibiotics.

The results revealed only significant outcomes for brepocitinib: 51.9% achieved HiSCR versus 33.3% on placebo (P_one-sided= 0.0298). The rate of brepocitinib responders differed according to stage with 59.4% responders in Hurley stage 2 and 40% in Hurley stage 3. In addition, brepocitinib significantly reduced the percentage of patients with ≥1 flare compared with placebo (-22.3%, P_one-sided= 0.0064). All agents were deemed generally safe and well tolerated, as most observed adverse events were mild or moderate.

“We have been able to test 3 different modalities, this tells us some things about the pathophysiology for HS, which is a very profoundly intense inflammatory process and may require multiple modalities of action to get it under control,” Prof. Kimball expressed as part of her conclusion.

1. Kimball A. Efficacy and safety of 3 different kinase inhibitors: brepocitinib (TYK2/JAK1 inhibitor), IL-1 receptor associated kinase 4 (IRAK4) inhibitor, and Tyrosine kinase 2 (TYK2) inhibitor in patients with moderate to severe hidradenitis suppurativa in a Phase 2a umbrella study. 3J, EADV Congress 2022, Milan, Italy, 7–10 September.

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Posted on 5 November 202217 May 2024