JAK1 inhibition successful in hidradenitis suppurativa

The results of two phase 2 trials with a novel Janus kinase (JAK) 1 inhibitor showed a good safety profile in patients with moderate-to-severe hidradenitis suppurativa (HS).

Patient with HS experience painful inflammatory lesions and have a markedly reduced quality of life. The rationale for using a JAK inhibitor in this indication is that treatments targeting pro-inflammatory cytokine signalling may influence disease pathology and ameliorate symptoms of HS. “There is an unmet medical need for an oral treatment for these patients,” said Dr Afsaneh Alavi (Mayo Clinic, USA) during the presentation of the results from two phase 2 studies with the JAK1 inhibitor INCB054707 [1]. INCB054707 is an oral, small-molecule, JAK1 inhibitor with 52-fold greater selectivity for JAK1 versus JAK2.

Study 1 was an open-label, single-arm study (NCT03569371), and study 2 was a placebo-controlled, dose-escalation study (NCT03607487) in which 3 doses of the JAK inhibitor were tested (i.e. 30 mg, 60 mg, and 90 mg). The primary endpoint of both studies was safety and tolerability, but efficacy endpoints were assessed as secondary study outcomes. All 45 participants (age 18-75) had moderate-to-severe HS (i.e. Hurley stage II/III) for at least 6 months. They had lesions in at least 2 different anatomic locations and a total abscess and inflammatory nodule (AN) count of ≥3.

Regarding safety, all occurring treatment-emergent adverse events were mild or moderate. One patient in study 1 discontinued due to upper respiratory tract infection and fibromyalgia. In study 2, 4 patients (15.4%) treated with the highest dose of the JAK inhibitor experienced thrombocytopenia (defined as platelet count <150 x 10⁹/L), a known JAK inhibitor-related side effect. These patients interrupted their dose for up to 2 weeks. However, all platelet counts returned to levels above 150 x 10⁹/L, and the drug was restarted in these patients without sequelae.

In addition, the JAK1 inhibitor showed remarkable efficacy. An HS complete response was achieved by 43% of patients in study 1 and 88% of patients who received the highest dose in study 2. An HS complete response is defined as a ≥50% reduction in AN count with no increase in either abscess or draining fistula counts relative to baseline. “With regard to the AN count, we could even show a better dose-dependent response,” said Dr Alavi. An AN count of 0-2 was achieved by 63% of patients in the highest dose group. “All quality-of-life measures improved very nicely and significantly in a dose-dependent way,” according to Dr Alavi.

The researchers also performed a biomarker analysis of inflammatory mediators. According to this analysis, a significant drop in inflammatory markers was seen with increasing doses of the JAK inhibitor. “An improvement was seen as early as week 1,” Dr Alavi concluded. Further larger studies are warranted to back these preliminary results.

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   1. Alavi A. INCB054707, a Janus Kinase 1 inhibitor, for patients with moderate-to-severe hidradenitis suppurativa: Results from two 52-week phase 2 studies. Abstract 2665, EADV 2020 Virtual Congress, 29-31 Oct.

Posted on 17 December 202017 May 2024