PMID- 37731086 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240411 IS - 2193-8210 (Print) IS - 2190-9172 (Electronic) VI - 13 IP - 10 DP - 2023 Oct TI - Spesolimab Efficacy and Safety in Patients with Moderate-to-Severe Palmoplantar Pustulosis: A Multicentre, Double-Blind, Randomised, Placebo-Controlled, Phase IIb, Dose-Finding Study. PG - 2279-2297 LID - 10.1007/s13555-023-01002-1 [doi] AB - INTRODUCTION: We evaluated the anti-interleukin-36 receptor antibody spesolimab in patients with moderate-to-severe palmoplantar pustulosis (PPP). METHODS: This phase IIb trial comprised a loading dose period to week (W) 4, then maintenance dosing to W52. Patients were randomised 2:1:1:1:2 to subcutaneous spesolimab 3000 mg to W4 then 600 mg every 4 weeks (q4w), spesolimab 3000 mg to W4 then 300 mg q4w, spesolimab 1500 mg to W4 then 600 mg q4w, spesolimab 1500 mg to W4, 300 mg q4w to W16 then 300 mg every 8 weeks (q8w), or placebo switching to spesolimab 600 mg q4w at W16. The primary efficacy endpoint was percentage change from baseline in Palmoplantar Pustular Area and Severity Index (PPP ASI) at W16. Secondary endpoints included a Palmoplantar Pustular Physician's Global Assessment (PPP PGA) score of 0/1. Safety (including adverse events [AEs], local tolerability) was assessed. RESULTS: 152 patients were treated. The primary endpoint was not met; mean differences for spesolimab versus placebo ranged from - 14.6% (95% confidence interval [CI]: - 31.5%, 2.2%) to - 5.3% (95% CI: - 19.1%, 8.6%); none reached significance. At W16, 23 (21.1%) and two (4.7%) patients in the combined spesolimab and placebo groups, respectively, achieved PPP PGA 0/1 (mean difference 16.4%; 95% CI: 3.8%, 25.7%), increasing to 59 (54.1%; combined spesolimab) and 12 (27.9%; placebo switch to spesolimab) patients at W52. Non-Asian patients had significant improvements in the primary endpoint (mean difference - 17.7%; nominal P = 0.0394) and PPP PGA 0/1 at W16 with spesolimab versus placebo. Rates of AEs and AE-related discontinuations were similar for spesolimab and placebo. Local tolerability events and injection-site reactions were more frequent with spesolimab than placebo. CONCLUSION: The primary objective to demonstrate a non-flat dose-response relationship and proof-of-concept was not achieved; improvements with spesolimab occurred in secondary endpoints and in non-Asian patients, indicating potential modest benefits. Spesolimab was generally well tolerated (ClinicalTrials.gov NCT04015518). CI - (c) 2023. The Author(s). FAU - Burden, A David AU - Burden AD AUID- ORCID: 0000-0001-7395-9931 AD - School of Infection and Immunity, University of Glasgow, Glasgow, UK. David.Burden@glasgow.ac.uk. FAU - Bissonnette, Robert AU - Bissonnette R AUID- ORCID: 0000-0001-5927-6587 AD - Innovaderm Research Inc., Montreal, QC, Canada. FAU - Navarini, Alexander A AU - Navarini AA AUID- ORCID: 0000-0001-7059-632X AD - Department of Dermatology, University Hospital Basel, Basel, Switzerland. FAU - Murakami, Masamoto AU - Murakami M AUID- ORCID: 0000-0003-3923-5096 AD - Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan. FAU - Morita, Akimichi AU - Morita A AUID- ORCID: 0000-0001-8372-3754 AD - Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. FAU - Haeufel, Thomas AU - Haeufel T AD - Boehringer Ingelheim International GmbH, Ingelheim, Germany. FAU - Ye, Binqi AU - Ye B AUID- ORCID: 0000-0003-2276-1217 AD - Boehringer Ingelheim (China) Investment Corporation Limited, Shanghai, People's Republic of China. FAU - Baehner, Frank AU - Baehner F AD - Boehringer Ingelheim International GmbH, Ingelheim, Germany. FAU - Terui, Tadashi AU - Terui T AUID- ORCID: 0000-0002-0275-4311 AD - Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan. LA - eng SI - ClinicalTrials.gov/NCT04015518 PT - Journal Article DEP - 20230920 PL - Switzerland TA - Dermatol Ther (Heidelb) JT - Dermatology and therapy JID - 101590450 CIN - Dermatol Ther (Heidelb). 2024 Apr;14(4):1063-1065. PMID: 38594568 PMC - PMC10539230 OAB - A clinical trial of spesolimab for patients with palmoplantar pustulosis. Palmoplantar pustulosis (PPP) is a painful, difficult-to-treat skin disease that is found on patients' palms and the soles of their feet. In this clinical trial, we studied an injected medicine called spesolimab for treating patients with PPP. Patients were split into five groups; four groups received different doses of spesolimab and one received placebo (an injection without spesolimab). After 16 weeks, patients receiving placebo switched to spesolimab. We measured the body area affected by PPP and how severe PPP was at week 16. Patients' doctors also assessed skin affected by PPP. At 16 weeks of treatment, there was no significant difference between spesolimab and placebo in terms of the PPP-affected area and severity. However, more patients had clear or almost clear skin with spesolimab than placebo. Among non-Asian patients, more showed an improvement in their PPP with spesolimab than with placebo; this was not the case with Asian patients. Patients taking spesolimab or placebo reported side effects, of which the most common were colds, aches and headaches. More patients receiving spesolimab reported a reaction at the injection site compared with placebo. We monitored patients for up to 1 year, and results remained similar. We showed that spesolimab may have a modest effect on the body area affected by PPP, as well as the severity of PPP, and did not seem to cause more side effects than placebo, except for reactions at the injection site. OABL- eng OTO - NOTNLM OT - Adverse effects OT - Dose-finding OT - Palmoplantar psoriasis OT - Palmoplantar pustular psoriasis OT - Palmoplantar pustulosis OT - Proof-of-concept OT - Pustulosis OT - Spesolimab OT - Treatment outcomes COIS- ADB reports receiving consulting fees from AbbVie, Almirall, BMS, Boehringer Ingelheim, Celgene, Bristol Myers Squibb, Eli Lilly, Janssen, LEO Pharma, Novartis and Union Chimique Belge (UCB) and payment or honoraria for lectures and presentations from Almirall, Boehringer Ingelheim, Eli Lilly and Janssen. RB is an advisory board member, consultant, speaker or investigator and/or received honoraria/grants from AbbVie, Almirall, AnaptysBio, Arcutis, Aristea, Bausch Health/Valeant, Boehringer Ingelheim, Boston Pharma, BMS, Dermavant, Eli Lilly, Escalier, Janssen, Kineta, Kyowa Kirin, LEO Pharma, Pfizer, Regeneron, Sienna and UCB and is also an employee and shareholder of Innovaderm Research. AAN declares being a consultant and advisor and/or receiving speaking fees/grants and/or served as an investigator in clinical trials for AbbVie, Almirall, Amgen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GlaxoSmithKline, LEO Pharma, Janssen-Cilag, Merck Sharp & Dohme, Novartis, Pfizer, Sandoz, Sanofi, Serono and UCB. MM reports receiving research grants and/or honoraria and/or serving as an investigator in clinical trials for AbbVie, Amgen, Aristea Therapeutics, BMS, Boehringer Ingelheim, Celgene, Eisai, Eli Lilly, Janssen, Kyowa Kirin, Maruho, Novartis, Taiho and Torii. AM reports receiving research grants, consulting fees and/or speaker's fees from AbbVie, Boehringer Ingelheim, Celgene, Eisai, Eli Lilly, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nichi-Iko, Nippon Kayaku, Novartis, Sun Pharmaceutical Industries, Taiho Pharmaceutical, Torii Pharmaceutical and Ushio. TT has received honoraria for speaking and consultancy from AbbVie, Eisai, Novartis, Janssen Pharmaceutical, Maruho, Taiho, Eli Lilly, BMS and Mitsubishi Tanabe Pharma. TH, BY and FB are employees of Boehringer Ingelheim. The authors met criteria for authorship as recommended by the ICMJE. The authors did not receive payment related to the development of this manuscript. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. EDAT- 2023/09/21 06:42 MHDA- 2023/09/21 06:43 PMCR- 2023/09/20 CRDT- 2023/09/21 00:18 PHST- 2023/06/23 00:00 [received] PHST- 2023/08/02 00:00 [accepted] PHST- 2023/09/21 06:43 [medline] PHST- 2023/09/21 06:42 [pubmed] PHST- 2023/09/21 00:18 [entrez] PHST- 2023/09/20 00:00 [pmc-release] AID - 10.1007/s13555-023-01002-1 [pii] AID - 1002 [pii] AID - 10.1007/s13555-023-01002-1 [doi] PST - ppublish SO - Dermatol Ther (Heidelb). 2023 Oct;13(10):2279-2297. doi: 10.1007/s13555-023-01002-1. Epub 2023 Sep 20.