An IL-1 blocker helped hard-to-treat hidradenitis — but its lowest dose lost to placebo

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease — painful, recurring abscesses and tunnels in the armpits, groin and other skin folds — with few effective treatments. For patients whose disease keeps flaring after a tumour necrosis factor (TNF) inhibitor stops working, the options run out quickly. A phase 2 trial has now tested lutikizumab, an antibody that blocks two inflammatory signals at once, in exactly that hard-to-treat group, and the results are genuinely mixed: two of three doses beat placebo, one did not, and placebo itself performed better than the word "placebo" might suggest [s1].

The drug and the trial

Lutikizumab is a dual-variable-domain antibody that neutralises both interleukin-1 alpha and interleukin-1 beta, cytokines implicated in the inflammation of HS [s1]. The trial, registered as NCT05139602 and funded by AbbVie, which is developing the drug, was a phase 2, double-blind, placebo-controlled study run at 45 sites across eight countries or territories — Australia, Canada, Germany, Greece, Japan, Puerto Rico, Spain and the United States — between December 2021 and November 2023 [s1][s2].

Adults with HS for at least 12 months who had failed anti-TNF therapy were randomised 1:1:1:1 to one of four arms: lutikizumab 300 mg weekly; lutikizumab 300 mg every other week; lutikizumab 100 mg every other week; or placebo weekly, each given through week 16 [s1]. The primary endpoint was the Hidradenitis Suppurativa Clinical Response at the 50% threshold — HiSCR50 — at week 16, meaning at least a halving of abscess and inflammatory-nodule counts without new abscesses or draining tunnels [s1].

What it found

In all, 153 participants received at least one dose; 61.4% were women, the mean age was 40.5 years (range 19 to 75), and 70.6% had Hurley stage III disease, the most severe form [s1]. This was, in other words, a sick and treatment-refractory population.

At week 16, HiSCR50 was reached by 48.7% of patients on 300 mg weekly, 59.5% on 300 mg every other week, and 27.0% on 100 mg every other week, compared with 35.0% on placebo [s1]. Using a Bayesian analysis, the trial estimated the posterior probability of a positive treatment effect versus placebo at 89.3% for the 300 mg weekly dose, 98.5% for the 300 mg every-other-week dose, and just 22.8% for the 100 mg dose [s1]. On a secondary measure of skin pain, among patients who started with at least moderate pain, 34.5% on the 300 mg every-other-week dose and 34.8% on the 300 mg weekly dose achieved a meaningful pain reduction, versus 12.9% on placebo [s1].

On safety, the trial reported no deaths and no treatment-emergent events of neutropenia, serious hypersensitivity reactions, major adverse cardiovascular events, or opportunistic infections [s1]. That clean short-term safety picture matters for a drug that blocks interleukin-1 signalling, where infection and blood-count effects are the standing concerns — though 16 weeks is far too short to rule them out.

How to read it

Two things stand out, and they pull in opposite directions. The higher doses produced a clinically plausible and statistically supported benefit in a population with almost nothing left to try, which is the encouraging half [s1]. But the lowest dose barely differed from placebo, and the placebo arm itself reached HiSCR50 in just over a third of patients — a high bar that reflects both the fluctuating natural course of HS and the attention patients receive in a trial [s1]. A large placebo response makes it harder to be sure how much of the drug effect is the drug.

The limits are those of an early trial. This was phase 2, sized to detect a signal rather than to settle efficacy, and it leaned on a Bayesian framework that reports probabilities of benefit rather than a single pass-or-fail p-value [s1]. Follow-up ran only to week 16, so durability is unknown, and the trial was funded and run by the drug's manufacturer [s1][s2]. None of this is disqualifying for a phase 2 study — it is what phase 2 is for — but it means the result is a reason to run a larger phase 3 trial, not to draw conclusions about where lutikizumab belongs in treatment.

What to watch

The questions now are whether a phase 3 trial confirms the every-other-week 300 mg dose as the one to carry forward, how long responses last, and whether the drug holds up against an unusually responsive placebo group [s1][s2]. This article describes research and is not medical advice; treatment of hidradenitis suppurativa is a decision for a dermatologist.

Sources

• Lutikizumab in Adults With Moderate to Severe Hidradenitis Suppurativa After Anti-TNF Therapy Failure: A Phase 2 Randomized Clinical Trial — JAMA Dermatology, 1 May 2026
• A Study to Assess Lutikizumab (ABT-981) in Moderate to Severe Hidradenitis Suppurativa After Anti-TNF Failure (NCT05139602) — ClinicalTrials.gov