Broad spectrum of emerging therapies in HS

Many different targets are being investigated for patients with hidradenitis suppurativa (HS). Dr Kelsey van Straalen (Erasmus Medical Centre, the Netherlands) discussed some of these options and strategies to further enhance response rates for this challenging patient population [1].

“HS is a complex disease, becoming even more complex as the disease progresses,” noted Dr Kelsey van Straalen (Erasmus Medical Centre, the Netherlands). “In addition, the disease is highly heterogeneous. Therefore, therapies need to be adjusted to the individual and their stage of the disease.” Dr van Straalen discussed the broad spectrum of emerging therapies for HS. The currently approved biologic therapies for HS are adalimumab (2015), secukinumab (2023), and bimekizumab (2024), yielding HiSCR50 response rates between 42% and 57% among patients with moderate-to-severe HS [2,3,4]. “Thus, about half of the patients reach a 50% improvement with these therapies,” said Dr van Straalen. “This is not exactly optimal. On the bright side, many new targets are being investigated.”

Currently,  4 targets are being evaluated in phase 3 studies and 18 targets in phase 2 trials. “It is encouraging to see that so many targets are being tested for such a heterogeneous disease,” said Dr van Straalen. She highlighted some of the agents being assessed in phase 3 studies.

“B-cells and plasma cells are abundant in chronic lesional HS,” Dr van Straalen explained. Remibrutinib, a BTK inhibitor targeting B-cells, was associated with a simplified HiSCR response rate of 72.7% after 12 weeks of therapy in 33 patients with HS [5]. This agent is currently under evaluation in a phase 3 trial. Dr van Straalen also noted that IL-1 is another promising target in HS. The IL-1 inhibitor lutikizumab achieved HiSCR50 response rates between 48.7% and 59.5% in 153 patients with moderate-to-severe HS in a phase 2 trial [6]. “The phase 3 study is still ongoing,” she added.

These response rates are promising, but not yet the transformational breakthrough the community hopes for. Dr van Straalen suggested that these drugs may be too targeted, acting only on parts of the disease mechanism.  “Maybe we should move to broader-acting agents,” she said. JAK inhibitors such as upadacitinib and povorcitinib have broader mechanisms-of-action and yielded HiSCR50 response rates of 40%-50% in phase 2 trials [7,8].

Another strategy to improve response rates is the combination of novel therapies. “There are currently 2 phase 2 studies exploring this approach,” said Dr van Straalen. “One investigates tibulizumab, a bispecific IL-17A and BAFF inhibitor, while the other evaluates a dual TNF and OX40L inhibitor.” Furthermore, improved patient stratification is needed to match the right therapy to the right patient, which is especially important given the heterogeneity of HS.

Finally, Dr van Straalen presented a retrospective study comparing HS patients treated with adalimumab plus the antibiotics clindamycin and rifampicin (n=31) to those receiving monotherapy (n=31). After 12 weeks, HiSCR response rates were 86% in the combination group and 41% in the monotherapy group. Additionally, draining tunnel counts were significantly reduced in the combination arm [9]. “These findings suggest that we should consider targeting the microbial component of HS,” said Dr van Straalen. “We should not only think about combining anti-inflammatory drugs with other anti-inflammatory agents, but also with anti-microbial agents.”

1. Emerging therapies on the horizon. SPIN Dermatology Congress, Paris, France, 2-4 July 2025
2. Kimball AB, et al. NEJM. 2016;375:422-434
3. Kimball AB, et al. Lancet. 2023;401:747-761
4. Kimball AB, et al. Lancet. 2024;403:2504-2519
5. Kimball AB. Oral presentation, 2024 AADD Annual Meeting, 8-12 March, San Diego, USA.
6. https://news.abbvie.com/2024-01-08-Lutikizumab-Showed-Positive-Results-in-a-Phase-2-Trial-of-Adults-with-Moderate-to-Severe-Hidradenitis-Suppurativa-as-Program-Advances-to-Phase-3, visited on 8 August 2025
7. Ackermann LS, et al. JAAD. 2025;92:1252-1260
8. Kirby JS, et al. JAAD. 2024;90:521-529
9. Aarts P, et al. JEADV. 2024;38(5):904-909

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Posted on 21 August 2025