Characteristic Spesolimab (n=35) Placebo (n=18) Age, years, mean (SD) 43.2 (12.1) 42.6 (8.4) Female, n (%) 21 (60.0) 15 (83.3) Race, n (%) Asian 16 (45.7) 13 (72.2) White 19 (54.3) 5 (27.8) BMI, kg/m2, mean (SD) 27 (8) 26 (10) IL36RN mutation positive*, n (%) 8 (22.9) 6 (33.3) GPPGA total score, n (%) 3 (moderate) 28 (80.0) 15 (83.3) 4 (severe) 7 (20.0) 3 (16.7) GPPGA pustulation subscore, n (%) 2 (mild) 6 (17.1) 5 (27.8) 3 (moderate) 16 (45.7) 7 (38.9) 4 (severe) 13 (37.1) 6 (33.3) Pain VAS, median (IQR) 79.8 (70.5–87.8) 70.0 (50.0–89.4) JDA GPP severity index, n (%) Mild 9 (25.7) 5 (27.8) Moderate 19 (54.3) 8 (44.4) Severe 4 (11.4) 4 (22.2) Missing 3 (8.6) 1 (5.6) Mean, SD 7.9 (3.0) 8.4 (2.8) Median, (min, max) 8.0 (2, 14) 8.0 (4, 14) Medication for GPP prior to randomization, n (%)† 18 (51.4) 9 (50.0) Clobetasol propionate 5 (14.3) 1 (5.6) Acitretin 4 (11.4) 1 (5.6) Cyclosporin 2 (5.7) 3 (16.7) Betamethasone valerate 2 (5.7) 2 (11.1) Methotrexate 1 (2.9) 3 (16.7) Betamethasone dipropionate 1 (2.9) 2 (11.1) Betamethasone; calcipotriol 2 (5.7) 1 (5.6) Emulsifying wax; paraffin, liquid, white soft paraffin 1 (2.9) 2 (11.1) Subgroup (n/N)* Response rate, Risk difference % of patients (95% CI) Overall (19/35 vs 1/18) 54.3 vs 5.6 0.487 (0.215–0.672) Baseline GPPGA total score 3 (16/28 vs 1/15) 57.1 vs 6.7 0.505 (0.163–0.706) 4 (3/7 vs 0/3) 42.9 vs 0.0 0.429 (−0.343–0.816) Presence of plaque psoriasis at baseline No (15/29 vs 1/15) 51.7 vs 6.7 0.451 (0.117–0.659) Yes (4/6 vs 0/3) 66.7 vs 0.0 0.667 (−0.109–0.957) Baseline GPPGA pustulation subscore <4 (12/22 vs 1/12) 54.5 vs 8.3 0.462 (0.089–0.697) =4 (7/13 vs 0/6) 53.8 vs 0.0 0.538 (0.070–0.808) Baseline JDA GPP severity index Mild or moderate (13/28 vs 1/13) 0.387 (0.038–0.614) Severe (4/4 vs 0/4) 100.0 vs 0.0 1.000 (0.261–1.000) Background medication before randomization No (14/20 vs 1/10) 70.0 vs 10.0 0.600 (0.177–0.823) Yes (5/15 vs 0/8) 33.3 vs 0.0 0.333 (−0.069–0.616) Sex Female (11/21 vs 1/15) 52.4 vs 6.7 0.457 (0.151–0.693) Male (8/14 vs 0/3) 57.1 vs 0.0 0.571 (−0.191–0.823) Race Asian (10/16 vs 1/13) 62.5 vs 7.7 0.548 (0.173–0.798) White (9/19 vs 0/5) 47.4 vs 0.0 0.474 (−0.073–0.716) BMI <25 kg/m2 (9/15 vs 0/9) 60.0 vs 0.0 0.600 (0.204–0.837) 25 to <30 kg/m2 (5/10 vs 1/6) 50.0 vs 16.7 0.333 (−0.231–0.713) ≥30 kg/m2 (5/10 vs 0/3) 50.0 vs 0.0 0.500 (−0.215–0.826) IL36RN mutation positive† No (9/21 vs 0/11) 42.9 vs 0.0 0.429 (0.081–0.660) Yes (7/8 vs 1/6) 87.5 vs 16.7 0.708 (0.126–0.960) Favors placebo Favors single-dose IV spesolimab 900 mg −0.50 −0.25 0.00 0.25 0.50 0.75 1.00 1.25 46.4 vs 7.7 Subgroup (n/N)* Response rate, Risk difference % of patients (95% CI) Overall (15/35 vs 2/18) 42.9 vs 11.1 0.317 (0.022–0.527) Baseline GPPGA total score 3 (13/28 vs 2/15) 46.4 vs 13.3 0.331 (0.000–0.564) 4 (2/7 vs 0/3) 28.6 vs 0.0 0.286 (−0.418–0.710) Presence of plaque psoriasis at baseline No (12/29 vs 2/15) 41.4 vs 13.3 0.280 (−0.044–0.513) Yes (3/6 vs 0/3) 50.0 vs 0.0 0.500 (−0.283–0.902) Baseline GPPGA pustulation subscore <4 (9/22 vs 1/12) 40.9 vs 8.3 0.326 (−0.025–0.574) =4 (6/13 vs 1/6) 46.2 vs 16.7 0.295 (−0.206–0.649) Baseline JDA GPP severity index Mild or moderate (9/28 vs 2/13) 32.1 vs 15.4 0.168 (−0.160–0.416) Severe (4/4 vs 0/4) 100.0 vs 0.0 1.000 (0.261–1.000) Background medication before randomization No (12/20 vs 2/10) 60.0 vs 20.0 0.400 (−0.019–0.685) Yes (3/15 vs 0/8) 20.0 vs 0.0 0.200 (−0.176–0.481) Sex Female (10/21 vs 2/15) 47.6 vs 13.3 0.343 (0.026–0.604) Male (5/14 vs 0/3) 35.7 vs 0.0 0.357 (−0.352–0.665) Race Asian (8/16 vs 2/13) 50.0 vs 15.4 0.346 (−0.031–0.647) White (7/19 vs 0/5) 36.8 vs 0.0 0.368 (−0.178–0.619) BMI <25 kg/m2 (8/15 vs 0/9) 53.3 vs 0.0 0.533 (0.118–0.787) 25 to <30 kg/m2 (3/10 vs 2/6) 30.0 vs 33.3 −0.033 (−0.532–0.430) ≥30 kg/m2 (4/10 vs 0/3) 40.0 vs 0.0 0.400 (−0.313–0.755) IL36RN mutation positive† No (6/21 vs 1/11) 28.6 vs 9.1 0.195 (–0.151–0.454) Yes (6/8 vs 1/6) 75.0 vs 16.7 0.583 (0.018–0.902) Favors placebo Favors single-dose IV spesolimab 900 mg −0.50 −0.25 0.00 0.25 0.50 0.75 1.00 1.25 PURPOSE To investigate the consistency of the spesolimab treatment effect by conducting a subgroup analysis of the primary and key secondary endpoints from the Effisayil 1 study, according to patient demographics and clinical characteristics at baseline. Baseline demographics and clinical characteristics The placebo arm included a higher proportion of female and Asian patients than the spesolimab arm; clinical characteristics were generally balanced between study arms Subgroup analysis of GPPGA total score of 0 or 1 at Week 1 The efficacy of spesolimab (GPPGA pustulation subscore of 0 or 1) was consistent across patient subgroups Missing values or any use of other medication for GPP within the first week of the trial were regarded as non-response for the analysis of these endpoints. *Single-dose IV spesolimab 900 mg vs placebo; subgroup analysis by age was not performed as only 2 patients were aged ≥65 years; †Patients who were homozygous or heterozygous for an IL36RN mutation were considered positive. Efficacy of spesolimab for the treatment of GPP flares across prespecified patient subgroups in the Effisayil 1 study A. David Burden1, Yukari Okubo2, Min Zheng3, Diamant Thaçi4, Peter van de Kerkhof5, Na Hu6, Christian Thoma7, Siew Eng Choon8 1Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK; 2Department of Dermatology, Tokyo Medical University, Tokyo, Japan; 3Department of Dermatology, Second Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang, China; 4Universitat Zu Luebeck, Lubeck, Germany; 5Department of Dermatology, Radboud University, Nijmegen, the Netherlands; 6Boehringer Ingelheim (China) Investment Co., Ltd, Shanghai, China; 7Boehringer Ingelheim International GmbH, Biberach, Germany; 8Department of Dermatology, Hospital Sultanah Aminah, Clinical School Johor Bahru, Monash University Malaysia, Subang Jaya, Malaysia INTRODUCTION • GPP is a rare and potentially life-threatening autoimmune disease characterized by recurrent flares of widespread sterile pustules, with or without systemic inflammation1,2 • Effisayil 1 (NCT03782792) was a multicenter, randomized, double-blind, placebo-controlled study of spesolimab, an anti-IL-36 receptor antibody, in patients presenting with a GPP flare. Within 1 week of a single dose of spesolimab, rapid pustular and skin clearance was observed compared with placebo3 − Primary endpoint (GPPGA pustulation subscore of 0; no visible pustules): 54% vs 6% (one-sided p<0.001) − Key secondary endpoint (GPPGA total score of 0 or 1; clear or almost clear skin): 43% vs 11% (one-sided p=0.0118) CONCLUSIONS • Estimates of spesolimab treatment effect in each patient subgroup were generally similar to those of the overall population for both the primary and key secondary endpoints • The efficacy of spesolimab (pustular and skin clearance) compared with placebo was consistent across all prescribed subgroups • However, it should be noted that several subgroups had very few patients • These data provide further evidence supporting the use of spesolimab to treat all patients presenting with a GPP flare METHODS • The efficacy of spesolimab was evaluated in prescribed patient subgroups from Effisayil 1, if at least 2 categories of the subgroup included ≥5 patients: sex, age, race, BMI, GPPGA pustulation subscore at baseline, GPPGA total score at baseline, JDA GPP severity score at baseline, presence of plaque psoriasis at baseline, and IL36RN status • Scan the QR code at the bottom of this poster to see full details of the Effisayil 1 study design3,4 RESULTS Subgroup analysis from the Effisayil 1 study showed that the efficacy of spesolimab (pustular and skin lesion clearance) was consistent across all prespecified patient populations, including those with or without IL36RN mutations Genotyping data were available for 46 patients. DNA sequencing was not performed in 7 patients. *Patients who were homozygous or heterozygous for an IL36RN mutation were considered positive. †Background medication for GPP in at least 3 patients of the overall population. Forest plot of risk difference for GPPGA total score of 0 or 1 at Week 1 Subgroup analysis of GPPGA pustulation subscore of 0 at Week 1 Missing values or any use of other medication for GPP within the first week of the trial regarded as non-response for the analysis of these endpoints. *Single-dose IV spesolimab 900 mg vs placebo; subgroup analysis by age was not performed as only 2 patients were aged ≥65 years. †Patients who were homozygous or heterozygous for an IL36RN mutation were considered positive. Forest plot of risk difference for GPPGA pustulation subscore of 0 at Week 1 The efficacy of spesolimab (GPPGA pustulation subscore of 0) was consistent across patient subgroups Abbreviations BMI, body mass index; CI, confidence interval; FDA, U.S. Food and Drug Administration; GPP, generalized pustular psoriasis; GPPGA, Generalized Pustular Psoriasis Physician Global Assessment; IL-36, interleukin-36; IQR, interquartile range; IV, intravenous; JDA, Japanese Dermatological Association; SD, standard deviation; pain VAS, pain visual analog scale. References 1. Navarini AA, et al. J Eur Acad Dermatol Venereol 2017;31:1792–1799; 2. Fujita H, et al. J Dermatol 2018;45:1235–1270; 3. Bachelez H, et al. N Engl J Med 2021;385:2431–2440; 4. Choon SE, et al. BMJ Open 2021;11:e043666. Disclosures & Acknowledgments The study was supported and funded by Boehringer Ingelheim. ADB declares paid consulting activities for AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, and UCB. YO declares grants or contracts from Eisai, Maruho Pharmaceutical, and Shiseido Torii; and consulting fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly, Janssen, JIMRO, Kyowa Kirin, LEO Pharma, Maruho Pharmaceutical, Novartis, Pfizer, Sanofi, Sun Pharmaceutical Industries, Taiho Pharmaceutical, Tanabe-Mitsubishi, Torii Pharmaceutical, and UCB. MZ declares receiving grants, consulting fees, and/or speaker’s fees from AbbVie, Boehringer Ingelheim, Janssen-Cilag, LEO Pharma China, Novartis, Pfizer, and Xian-Janssen. DT declares having attended advisory boards and/or received consultancy fees and/or receiving grants as an investigator from AbbVie, Almirall, Amgen, Beiersdorf, Bristol Meyers Squibb, Boehringer Ingelheim, DS-Pharma, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Maruho, Medac, MorphoSys, Norvartis, Pfizer, Regeneron Pharmacueticals, Inc., Samsung, Sandoz, Sanofi, Sun Pharmaceutical Industries, and UCB. PvdK received fees for consultancy service or lectureships from Almirall, AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant Sciences, Eli Lilly, Janssen, LEO Pharma, Novartis, and UCB. NH and CT are employees of Boehringer Ingelheim. SEC declares paid activities as an advisor, speaker, or consultant for AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Sanofi, and UCB. The authors met criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment related to the department of the poster. Boehringer Ingelheim was given the opportunity to review the poster for medical and scientific accuracy, as well as intellectual property considerations. Geetha Vilventhraraja of OPEN Health Communications (London, UK) provided writing, editorial, and formatting support, which was contracted and funded by Boehringer Ingelheim. Scan the QR code for an interactive, electronic device- friendly copy of the original presentation from AAD 2022 https://bit.ly/3qGWhdc Click the icon to access an interactive microsite, containing the original presentation from AAD 2022 Presented at Winter Clinical Dermatology Conference Hawaii® (January 13–18, 2023; Kohala Coast, HI, USA) and Winter Clinical Miami™ (February 17–20, 2023; Miami, FL, USA) Previously presented at the 80th American Academy of Dermatology (AAD) Annual Meeting (March 25–29, 2022; Boston, MA, USA)