High-dose subcutaneous spesolimab prevents GPP flares up to week 48

Compared with placebo, therapy with the IL-36 receptor antibody spesolimab resulted in a higher proportion of patients that achieved and maintained complete clearance of generalised pustular psoriasis (GPP) lesions over 48 weeks, according to a current analysis of the Effisayil 2 trial results. In addition, no patient receiving high-dose spesolimab had a flare after week 4.

GPP is a rare but potentially life-threatening inflammatory skin disease characterised by widespread eruption of sterile pustules, which has recently been reclassified as a superficial/epidermal neutrophilic disease [1–3]. The antibody spesolimab specifically targets the IL-36 receptor, which plays a key role in GPP pathogenesis, and is approved for the treatment of GPP flares.

Previously, spesolimab has been evaluated for the prevention of flares in the randomised, placebo-controlled, phase 2 Effisayil 2 trial (NCT04399837). Currently, Prof. Matthias Augustin (University Medical Center Hamburg-Eppendorf, Germany) presented an analysis of Effisayil 2, which assessed the effect of high-dose spesolimab (i.e. 600 mg loading dose followed by 300 mg every 4 weeks) or placebo on GPP lesions using both subscores and the total score of the GPP Physician Global Assessment (GPPGA) scale [4]. GPPGA subscores for erythema, pustulation, and scaling/crusting as well as GPPGA total score were compared between participants receiving high-dose spesolimab and placebo. At baseline, the subscores were balanced between the groups. “Only 23% of participants had an IL36RN mutation,” Prof. Augustin added.

After treatment initiation with spesolimab, the proportion of participants with a GPPGA score of 0 (i.e. 0 for all 3 components of erythema, pustulation, and scaling) increased, whereas the score remained similar in the placebo group at week 4. In addition, the proportion of participants with GPP flares was lower with high-dose spesolimab compared with placebo.

Moreover, the agent showed long-term efficacy in managing skin manifestations. A greater proportion of participants with a GPPGA total score of 0 was achieved and maintained with spesolimab compared with placebo over 48 weeks. The superiority of spesolimab was evident in each subscore compared with placebo up to week 48. Importantly, no new flares were observed with high-dose spesolimab after week 4.

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   1. Choon S, et al. Am J Clin Dermatol 2022;23(Suppl 1):S21–29.
   2. Burden AD, et al. Am J Clin Dermatol 2022;23 (Suppl 1):S39–50.
   3. Krueger J, et al. Am J Clin Dermatol 2022;23 (Suppl 1):S51–64.
   4. Augustin M. Effect of high-dose subcutaneous spesolimab on skin manifestations: Results from the pivotal Effisayil 2 trial of flare prevention in generalized pustular psoriasis. FC05.2, EADV Congress 2023, 11–14 October, Berlin, Germany.

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Posted on 28 November, 202322 February, 2024