Generalized pustular psoriasis: the new era of treatment with IL-36 receptor inhibitors

Generalized pustular psoriasis (GPP) is a rare yet severe variant of psoriasis, characterized by the eruption of superficial sterile pustules that appear suddenly and widely distributed, potentially life-threatening. It more commonly presents through recurrent acute flares triggered by stress, corticosteroid withdrawals, pregnancy, or infections. The pathogenesis of this disease is yet to be fully understood. Nevertheless, studies have suggested an important role of an IL-1 subfamily of cytokines, due to an imbalance of the IL-36 axis favoring of pro-inflammatory activity. The therapeutic intervention for this condition is still a challenge as its rarity and scarce available information contribute to the absence of specific treatment. Current options stand on small, open-label trials or follows standard treatment for plaque psoriasis. Spesolimab and imsidolimab are two IL-36 receptor inhibitors which completed phase 1 and 2 trials with a good efficacy and safety profile in the treatment of this disease, including in the fast control of its acute flares. The most common adverse events reported with spesolimab were mild to moderate infections, and imsidolimab was well tolerated. GPP clinical trials remain to have their small sample size as a major limitation, but IL-36 receptor inhibitors are promising therapeutic options currently under investigation.