For hidradenitis suppurativa (HS), the major clinical benefits of targeting tumor necrosis factor-like cytokine-1A (TL1A), interleukin-1 beta (IL-1 beta) alone, or both IL-1 alpha and IL-1 beta have been shown in separate controlled trials.

Words like “exciting” and “very promising” were used to describe the findings during late-breaker presentations at the European Academy of Dermatology and Venereology (EADV) 2026 Congress in Vienna. In all three cases, phase 3 trials are already underway or planned.

In the case of tulisokibart, a monoclonal antibody that targets TL1A, a solid dose-response was observed in a three-dose study. Of those taking the highest dose, 71% achieved the primary endpoint of a 50% or greater reduction in the total count of abscesses and nodules, a commonly used endpoint known as the Hidradenitis Suppurativa Clinical Response (HiSCR50).

“This is an exciting new day. This is the first time that we have seen what TL1A inhibition can do,” reported Alexa B. Kimball, MD, MPH, professor of dermatology and a researcher at Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Tulisokibart Studied in Dose-Ranging Trial

In this multicenter phase 2b study, 149 patients with moderate to severe HS were randomized to one of three doses of tulisokibart or placebo. In the tulisokibart groups, all patients received a loading dose (960 mg in the two higher-dose groups and 480 mg in the low-dose group) followed by 480 mg every 2 weeks (high dose), 480 mg every 4 weeks (medium dose), or 240 mg every 4 weeks (low dose). 

For the primary endpoint of HiSCR50 at week 16, the 71% response rate in the high-dose group (P = .001) and the 64% response rate in the medium-dose group (P = .012) were significant relative to the 41% response rate in the placebo group. The 53% response rate in the low-dose group did not reach significance. Curves separated for the two higher doses from placebo at about 4 weeks.

For the more rigorous endpoint of HiSCR75, rates in the two highest-dose groups of 41% and 40%, respectively, were also significant relative to the 15% response rate in the placebo group.

The improvement in the Dermatology Life Quality Index (DLQI) of 5.6 points with high-dose tulisokibart was consistent with the greater activity relative to the 3.5-point improvement with the medium dose and 2.6-point improvement in the placebo group.

Consistent with other trials of tulisokibart — which is being evaluated for several other autoimmune disorders including rheumatoid arthritis, psoriatic arthritis, and inflammatory bowel disease — the safety data were “clean,” with no signals suggesting a need for closer monitoring, according to Kimball.

In the phase 2 LOTUS trial of abdakibart, a monoclonal antibody that targets IL-1 beta, 167 patients with moderate to severe HS were randomized to one of two doses or placebo. About 40% of patients had received prior biologics.

HiSCR75: Primary Endpoint for Abdakibart

For the relatively rigorous primary endpoint of HiSCR75, both the 150-mg abdakibart dose administered every 2 weeks (42.2%; P = .015) and the 300-mg dose administered every 4 weeks (42.9%; P = .015) outperformed placebo (25.6%).

“These findings validate IL-1 beta as a promising new mechanism of action for the control of HS,” reported principal investigator Martina L. Porter, MD, vice chair of research and academics in the department of dermatology at Beth Israel Deaconess.

Differences between abdakibart and placebo on the International Hidradenitis Suppurativa Severity Score (IHS4) were even greater. IHS4 activity at 16 weeks was reduced by 15.9 points with the 300-mg dose (P = .002) and 14.5 points (P = .012) with the 150-mg dose relative to the 8.2-point reduction with placebo.

For IHS4-55 and IHS4-75 (≥ 55% and ≥ 75% reductions in IHS4), the greater responses in the active therapy groups were also significant for the two abdakibart doses relative to placebo. Of those taking the 300-mg and 150-mg doses, 59.5% (P = .001) and 57.8% (P = .003) had an IHS4-55 response vs 36% with placebo. Rates of an IHS4-75 response were 40.5% (P = .013) and 44.6% (P = .002) vs 23.3% with placebo.

For IHS4-90, the numerically higher rates of 21.4% for the 300-mg dose and 25.3% for the 150-mg dose were described as a trend relative to the rate of 14% with placebo.

The study also compared reductions in abscesses, inflammatory nodules, and draining tunnels (ANdT) count in the three groups. ANdT count fell by 6.0 points with placebo, 9.1 points (P = .42) with the 150-mg dose, and 10.4 points (P = .004) with the 300-mg dose of abdakibart. When assessed individually, the reductions relative to placebo for  inflammatory nodules (P = .006) and draining tunnels (P = .008), but not abscesses, were highly significant.

Again, like tulisokibart, the safety profile of abdakibart was characterized by Porter as “clean.” There were no substantial differences in the number or types of adverse events, and discontinuations due to an adverse event were lower with the 300-mg dose than placebo (1.2% vs 2.3%).

Phase 2 data for lutikizumab, a combined IL-1 alpha and IL-1 beta inhibitor, were published earlier this year. A new analysis of that 153-patient study combined with data from a 14-patient open-label biologic-naïve study was presented as a late-breaker during the congress. The results not only reinforce the benefit of this target in HS but also provide new insights on the mechanism of action.

Neutrophil Invasion Characterizes Lesional HS Skin

“In our analysis of these patients with moderate to severe HS, we were able to show that lesional skin relative to nonlesional skin is characterized by elevated neutrophil counts and pathogenic fibroblast subsets as well as IL-1 alpha/beta expression,” reported Johann E. Gudjonsson, MD, PhD, professor of dermatology at the University of Michigan, Ann Arbor.

The smaller 14-patient study showed lesional skin in patients with HS has a dramatic increase in neutrophil infiltration relative to nonlesional skin. Neutrophils are a primary source of IL-1 alpha/beta expression, as shown by this study and others, Gudjonsson explained.

When lesional skin was evaluated after treatment with lutikizumab in the larger dataset, neutrophil counts were substantially reduced, reaching 40% (P < .0001) at the highest dose, with an even greater 81.3% (P < .0001) reduction in IL-1 beta expression.

Other cytokines in the inflammatory pathway, such as IL-6 and high-sensitivity C-reactive protein (hsCRP) were also significantly reduced.

When placebo was compared to active therapy or when nonresponders were compared to lutikizumab responders, neutrophil counts and IL-1 alpha/beta expression were greatly reduced, supporting a correlation between reduction in neutrophils, inhibition of IL-1 alpha/beta expression, and the clinical benefit of lutikizumab.

Moreover, this correlation might be particularly important for some disease symptoms, according to Gudjonsson.

“By reducing neutrophil and pathogenic fibroblast activity, lutikizumab may mitigate aberrant extracellular matrix remodeling, thereby reducing fibrosis and tunnel formation in HS,” he said.

Despite the growth in approved therapeutic options for HS, Jo L.W. Lambert, MD, PhD, a professor of dermatology and venerology at Ghent University Hospital in Belgium, emphasized the still unmet need for patients with HS. A chair for one of the late-breaking sessions during which these data were presented, she emphasized the promise and excitement generated by the growing number of ways to target the disease.

Kimball has reported financial relationships with AbbVie, Acelyrin, AnaptysBio, Avalo, Boehringer Ingelheim, Bristol Myers Squibb, Cellarity, Citryll, CuraGen, Eli Lilly, Insight, Insmed, Janssen, Merck, MoonLake, Navigator, Neurocrine, Novartis, Nurix, Oruka, Pfizer, Propeller, Regeneron, Sanofi, Sonoma, Takeda, and UCB. Porter has reported financial relationships with AbbVie, Acelyrin, Alumis, AnaptysBio, Aristea, Bayer, Bristol Myers Squibb, Eli Lilly, Incyte, Janssen, MoonLake, Novartis, Pfizer, Prometheus Laboratories, Regeneron, Sanofi, Trifecta Clinical, Sonoma Bio, and UCB. Gudjonsson has reported financial relationships with AbbVie, Almirall, Anaptys Bio, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, Janssen, Kyowa Kirin, MiRagen, Novartis, Prometheus/Merck, Sun Pharma, and Timber Pharmaceuticals. Lambert has reported no potential conflicts of interest.

Ted Bosworth, a career medical writer based in New York City, has been covering advances in clinical medicine, including dermatology and oncology, for several decades.