Combined TYK2/JAK1 inhibition shows promise in hidradenitis suppurativa

Brepocitinib demonstrated significant efficacy in Hidradenitis Suppurativa Clinical Response (HiSCR) and flare reduction in hidradenitis suppurativa (HS).

3 experimental agents were investigated

A study design novel to dermatology was used to investigate 3 experimental agents with different modes of action versus placebo in a phase 2b study (NCT04092452) on patients with moderate-to-severe HS, i.e. Hurley stages 2 and 31. 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. Alexandra Kimball (Harvard Medical School, Boston, USA) explained.

The active study drugs included the IRAK4 inhibitor PF-06650833 (400 mg/d), the TYK2-inhibitor PF-06826647 (400 mg/d), and the TYK2/JAK 1 inhibitor brepocitinib (45 mg/d). 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 patient age in the various groups ranged from 37 to 40, Body Mass Index from 35.12 to 36.64, and 72.3% to 87.5% were women. Within the ethnically diverse population, 61.5% to 72.3% had Hurley stage 2, 20.8% to 23.4% were previous inadequate responders to anti-TNF, and 10.6% to 14.6% concomitantly used antibiotics.

The most effective agent also reduced % of patients with ≥1 flare

The results revealed the only significant results for brepocitinib: 51.9% achieved HiSCR versus 33.3% on placebo (Pone sided= 0.0298). The rate of brepocitinib responders differed according to stage with 59.4% responders in Hurley 2 and 40% in Hurley 3 stage. In addition, brepocitinib reduced the percentage of patients with ≥1 flare significantly compared with placebo (-22.3%, Pone sided= 0.0064). All agents were deemed generally safe and well tolerated, as the majority of 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. D2T01.3J, EADV Congress 2022, Milan, Italy, 7–10. September.