More therapy options are still lacking to manage most patients with hidradenitis suppurativa (HS) effectively. The next agents that approach approval will likely be IL-17 inhibitors.
“We have some kind of explosion of new studies in HS: around 140 studies are registered in clinical trials, and approximately half of them concern phase 1, 2, or 3,” Dr Axel Villani (University of Lyon, France) said in his opening remarks on pipeline treatments . Many of the different agents tested in HS can already be found in trials on psoriasis. “HS and psoriasis share some similarities in terms of molecular signature and inflammation, but they are not exactly the same,” Dr Villani pointed out.
Among the manifold possible treatment targets influencing the immune response in HS are IL-1, IL-17, IL-23, IL-36, and B-cells. Research on IL-1 includes 2 small studies on MABp1 (NCT02643654) and anakinra (NCT01558375), and a phase 2 trial on bermekimab (NCT03512275), in which the IL-1α inhibitor demonstrated significant efficacy with about 60% achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR50), both in participants who were anti-TNF naïve (P=0.02) or who had anti-TNF failure (P=0.04) [2–4]. In terms of IL-23 and IL-36, there is 1 active (NCT04876391) and 1 completed (NCT04762277) spesolimab study, but results have not been published yet. Moreover, the PDE4 inhibitor apremilast has been evaluated as a therapeutic agent in HS. Interesting results came from an investigation that followed responders (n=8) from a small study over 2 years and found prolonged responses at 1 and 2 years . B-cells and plasma cells are still controversial potential treatment targets in HS. “There is a lot of recruitment of plasma cells and B-cells in the skin at least at the acute phase of the disease, but the main concern is that we don’t know if they are protectors or pathogenic cells,” Dr Villani explained. Recently, Bruton’s and spleen tyrosine kinases have been proposed as possible subjects of further research .
IL-17 inhibitors may be the next available agents
To date, IL-17 inhibitors are the most advanced new therapies under development for HS. Published data on brodalumab, bimekizumab, and secukinumab is available . An open-label study on brodalumab (NCT04249713) included 10 participants who all reached HiSCR50, and 80% also showed a category change in International Hidradenitis Suppurativa Severity Score System (IHS4) . No adverse events of grade 1 or 3 were reported. Available bimekizumab results come from phase 2 trials . One study (NCT03248531) encompassed a placebo and a bimekizumab arm plus an adalimumab group as active control . At week 12, the results for HiSCR50, 75, and 90 were 24%, 11%, and 0% for placebo, 60%, 39%, and 17% for adalimumab, as compared with 57%, 50%, and 35% in the bimekizumab arm, respectively. Efficacy of bimekizumab was also seen in IHS4 score ameliorations. No new safety signals were found compared with the profile known from studies in other indications . Based upon these promising results, the phase 3 BE HEARD I study (NCT04242446) was initiated and is currently active. “When it comes to secukinumab, we are expecting to see the results perhaps at the upcoming EADV congress. Up to now, the data we have comes from a poster that clearly showed achievement of Physician Global Assessment (PGA) response and lower inflammatory lesions at week 16 compared with placebo,” Prof. Thrasyvoulos Tzellos (Nordland Hospital Trust, Norway) explained, as he presented the IL-17 data in a complementing talk. The phase 2 results are already available (NCT02421172). Furthermore, the phase 3 SUNRISE trial is underway (NCT03713632). “Most probably, we are talking about 2 drugs that will come to the market soon, hopefully,” Prof. Tzellos predicted.
- Villani A. Pipeline treatments: towards personalised medicine in HS? FS4, SPIN 2022 Congress, 06–08 July, Paris, France.
- Kanni T, et al. J Invest Dermatol. 2018;138:795-801.
- Tzanetakou V, et al. JAMA Dermatol. 2016;152:52-9.
- Gottlieb a, et al. J Invest Dermatol. 2020;140:1538-45.
- Aarts P, et al. J Am Acad Dermatol. 2021;85:258-60.
- Gudjonsson JE, et al. JCI Insight. 2020;5:e139930.
- Tzellos T. Hidradenitis Suppurativa: Pipeline and new concepts. FS4, SPIN 2022 Congress, 06–08 July, Paris, France.
- Frew JW, et al. J Am Acad Dermatol. 2020;83:1341-48.
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Table of Contents: SPIN 2022
Letter from the Editor
SPIN 2022 Highlights Podcast
IMIDs in Adults and Children: New Developments
Therapies for atopic dermatitis: still moving forward
Children with AD: high risk of bacterial infections in carriers of a filaggrin gene variant
Men on biologics report fewer adverse events than women
Conceptual framework of adverse drug reactions may improve treatment of patients with IMIDs
Psoriasis: The Beat Goes On
Systemic treatment for psoriasis: what is on the horizon?
Topical therapy in psoriasis: an important partner in combination therapy
GPP flares: pronounced undertreatment is common
IL-17A/F inhibitor bimekizumab shows higher response and maintenance rates compared with secukinumab
Paediatric psoriasis: ixekizumab beneficial in difficult-to-treat areas
Psoriasis patients see great benefit in achieving complete skin clearance
The Future Is Bright for Vitiligo
Predilection sites for skin signs of vitiligo disease activity determined
Where Are We Now in Hidradenitis Suppurativa
IHS4 better suited as an outcome measure in HS trials?
New treatments for HS: IL-17 inhibitors next in practice?
New Treatment Options in Alopecia Areata
Alopecia areata: light at the end of the tunnel
Alopecia areata pathogenesis: known genetic background, unknown environmental triggers
Best of the Posters
Psoriasis treatment: no elevation of MACE and VTE on deucravacitinib
Comorbid anxiety and depression may benefit from psoriasis treatment with certolizumab
Dose tapering in psoriasis is associated with a low relapse rate
Potential biomarker discovered for treatment response to ustekinumab