Inhibition of the Interleukin-36 Pathway for the Treatment of Generalized Pustular Psoriasis

Abstract

Inhibition of the Interleukin-36 Pathway for the Treatment of Generalized Pustular PsoriasisTo the Editor: Generalized pustular psoriasis is a rare, life-threatening disease characterized by recurrent flares of pustular, erythematous rashes. 1 In some patients with this disease, lossof-function mutations have been found in IL36RN, which encodes an interleukin-36-receptor antagonist.2,3 This finding suggests that the interleukin-36 pathway may be involved in the pathogenesis of this disorder.4 We report the results of a phase 1 proof-ofconcept study involving seven patients who presented with a generalized pustular psoriasis flare and were treated with a single, open-label, intravenous dose of BI 655130, a monoclonal antibody against the interleukin-36 receptor, 5 at 10 mg per kilogram of body weight (ClinicalTrials.govnumber, NCT02978690).(The study protocol is available with the full text of this letter at NEJM.org.)At baseline, all the patients were evaluated with the use of the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA), a physicianbased assessment of the severity of pustules, erythema, and scaling of generalized pustular psoriasis lesions.Each component is scored on a five-point scale, ranging from 0 (least severe) to 4 (most severe), and the average is calculated.(Details about scoring are provided in the Supplementary Appendix, available at NEJM.org.)All the patients had an average GPPGA score of 3 (moderate disease), with a pustule subscore of 2 to 4. Three patients had a homozygous IL36RN mutation, one of whom also had a heterozygous mutation in CARD14 (which has been linked to pustular skin disease), and four did not have any of the target mutations (IL36RN, CARD14, and AP1S3) (Table S1 in the Supplementary Appendix).After the infusion of the study drug, all the patients had adverse events that were graded as mild or moderate, and no serious adverse events