TOPLINE:

Lutikizumab, a dual interleukin (IL)-1 alpha/1 beta antagonist, improved clinical responses and pain outcomes in a phase 2 trial of adults with moderate-to-severe hidradenitis suppurativa (HS) who had failed anti-TNF therapy.

METHODOLOGY:

• A phase 2, double-blind, placebo-controlled randomized clinical trial evaluating lutikizumab was conducted at 45 sites across eight countries or territories (Australia, Canada, Germany, Greece, Japan, Puerto Rico, Spain, and the US) between December 2021 and November 2023.
• Researchers randomly assigned 153 adults (mean age, 40.5 years; 61.4% women) with moderate-to-severe HS for at least 12 months who experienced anti-TNF treatment failure 1:1:1:1 to receive 300 mg lutikizumab subcutaneously every week, 300 mg lutikizumab every other week, 100 mg lutikizumab every other week, or placebo every week for 16 weeks.
• Participants had a mean total abscess and inflammatory nodule count of 18.2 and mean draining tunnel count of 6.3, and 70.6% had Hurley stage III disease at baseline.
• The primary endpoint was achieving a Hidradenitis Suppurativa Clinical Response (HiSCR) 50 at week 16 (at least a 50% reduction from baseline in total abscess and inflammatory nodule count, with no increase in abscess or draining fistula count).
• The secondary endpoint was at least a 30% reduction and a reduction of 1 unit or more from baseline in Patient’s Global Assessment of skin pain (Numerical Rating Scale [NRS] 30) at week 16 among participants with a baseline NRS ≥ 3; other endpoints were achievement of HiSCR 75 and HiSCR 90 and changes in draining tunnels and Dermatology Life Quality Index (DLQI) scores from baseline.

TAKEAWAY:

• At week 16, 59.5% and 48.7% of participants who received 300 mg lutikizumab every other week and weekly, respectively, achieved HiSCR 50 compared with 35.0% of those on placebo. This endpoint was met by 27% of those receiving 100 mg lutikizumab every other week.
• Among those with NRS scores of at least 3, the pain response (NRS30) occurred in 34.5% and 34.8% receiving 300 mg lutikizumab every other week and weekly, respectively, compared with 12.9% of those receiving placebo.
• The proportion of patients achieving HiSCR 75 (38.5% and 45.9%, respectively, vs 17.5%) and HiSCR 90 (25.6% and 13.5%, respectively, vs 5.0%), the mean reduction in draining tunnels (-3.0 and -4.2, respectively, vs -1.5), and DLQI scores (least-squares mean difference, -3.8 and -3.4, respectively) also favored 300 mg lutikizumab weekly and every other week dosing, respectively, vs placebo.
• Treatment-emergent adverse events were similar across the treatment groups, with most being mild or moderate in severity, and there were no new safety signals.

IN PRACTICE:

The study results “suggest that lutikizumab, which neutralizes IL-1 alpha and IL-1 beta without interfering with IL-1RA [receptor antagonist]-mediated regulatory functions in the IL-1 pathway, is a therapeutic option to improve the signs and symptoms associated with HS,” the authors concluded. The results, they added, “support further clinical development of lutikizumab in HS.”

SOURCE:

The study was led by Alexa B. Kimball, MD, MPH, Harvard Medical School and the Clinical Laboratory for Epidemiology and Applied Research in Skin, Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, and was published online on March 18 in JAMA Dermatology.

LIMITATIONS:

The limitations included the relatively small sample size, short trial period, and some baseline imbalances between treatment groups.

DISCLOSURES:

This study was funded by AbbVie. Kimball and another three authors reported receiving grants, personal fees, and research support from AbbVie and several other pharmaceutical companies, Almirall, Eli Lilly, Janssen, MoonLake, Novartis, UCB, Boehringer Ingelheim, and Takeda. Some coauthors disclosed being employees of AbbVie, owning patents, or being on Foundations and Councils. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.