We investigated the immunogenicity of spesolimab, and its impact on PK, efficacy, and safety in patients with a GPP flare. Plasma samples were analysed from three trials. In trial 1 (proof of concept, NCT02978690), 7 patients received IV spesolimab 10 mg/kg. In trial 2 (Effisayil 1, NCT03782792), 53 patients were randomised 2:1 to receive IV spesolimab 900 mg or placebo on Day 1, with optional open-label (OL) spesolimab on Day 8 for persistent flare symptoms. At Week 12, patients could enroll into trial 3 (Effisayil ON, NCT03886246), a 5-year OL extension, to receive SC spesolimab 300 mg Q12W or Q6W; interim data are reported (N=39; September 2021). In trials 2 and 3, patients could receive additional IV spesolimab for a new flare. ADA data were available for 56 spesolimab-treated patients (trial 1, 6; trial 2, 50; trial 3, 36 from trial 2). In trial 2, ADA formed with a median onset of 2.3 weeks; 24% (12/50) had an ADA titer >4000 and were neutralising antibody-positive by Weeks 12–17. Higher immunogenicity responses (ADA titer >4000) were seen in females (30%; 10/33) compared with males (12%; 2/17). There was no impact on spesolimab PK in patients with ADA titers <4000, but spesolimab plasma concentrations reduced significantly at ADA titers >4000. Spesolimab efficacy was similar in ADA-positive and ADA-negative patients up to Week 12. Impact of ADAs on efficacy upon retreatment after Week 12 is to be determined, as 77% (30/39) of patients did not have a new flare in trial 3. There was no correlation between ADAs and hypersensitivity reactions. Treatment with spesolimab led to the development of ADAs with a maximum titer of >4000 in a limited proportion of patients by Weeks 12–17. There are minimal data on the impact of ADAs on efficacy upon retreatment.

ESDR094 - Characterisation of the immunogenicity of spesolimab in patients with a generalized pustular psoriasis (GPP) flare

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.