HS: Targeting IL-1 pathway potential option after anti-TNF failure

The IL-1α/1β antagonist lutikizumab showed promising results in patients with hidradenitis suppurativa (HS) who had insufficient treatment success with TNF blockers. In 2 out of 3 different regimens tested in phase 2, an HS Clinical Response of 50% (HiSCR50) was reached more often with lutikizumab than placebo.

“We see more and more HS patients in whom TNF blockers fail,” Prof. Falk G. Bechara (Ruhr-University Bochum, Germany) stated [1]. This phenomenon contributed to the design of a phase 2 trial (NCT05139602) of lutikizumab in patients with HS with prior unsuccessful anti-TNF therapy. The study included 153 participants randomised to weekly placebo or the IL-1α/1β antagonist at dosages of 300 mg bi-weekly, 100 mg bi-weekly, or 300 mg weekly over 16 weeks.

At baseline, the mean age in the 4 groups varied between 37.0 and 39.5 years, and the rate of women ranged from 53.8% to 67.6%. The highly affected study population included 64.9% to 74.4% of participants with severe HS (i.e. Hurley stage 3).

Compared with placebo, participants in the 2 high-dosed drug arms demonstrated greater rates in reaching the primary endpoint of HiSCR50: placebo 35%, 300 mg bi-weekly 59.5% (nominal P=0.027), and 300 mg weekly 48.7% (nominal P=0.197). HiSCR75 was seen in 17.5%, 45.9% (P=0.005), and 38.5% (P=0.031), respectively.

Skin pain, measured by numerical rating scale (NRS)30, improved in 12.9% of participants on placebo, in contrast to 22.2% (100 mg bi-weekly), 34.5% (300 mg bi-weekly), and 34.8% (300 mg weekly) of those on lutikizumab. Prof. Bechara also described that the improvement in draining fistula count was greater on both 300 mg regimens than on placebo.

Lutikizumab was considered safe and well-tolerated. The percentage of treatment-related events was similar between both treatment groups and placebo, with HS, diarrhoea, and headache being the most common. There were 2 serious adverse events in each of the study drug arms and 1 in the placebo group.

“For quite a long time, the IL-1 pathway has been assessed, but we did not really have clinical data; now, with lutikizumab, we have a new molecule to address this pathway,” Prof. Bechara highlighted.

Relevant readings:

• Hidradenitis suppurativa treatment with secukinumab linked to low immunogenicity (AAD 2024)
• BTK signalling as a novel target in hidradenitis suppurativa treatment (AAD 2024)

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   1. Bechara FG. A phase 2 multicentre, randomised, double-blind placebo-controlled study to evaluate the safety and efficacy of lutikizumab in adult patients with moderate to severe hidradenitis suppurativa who have failed anti-TNF therapy. LB1, 2024 AAD Annual Meeting, 8–12 March, San Diego, USA.

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Posted on 22 April, 20241 May, 2024