Indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis April Armstrong,1 Richard B. Warren,2 Yichen Zhong,3 Joe Zhuo,3 Allie Cichewicz,4 Ananth Kadambi,4 Daniela R. Junqueira,4 Tracy Westley,4 Renata Kisa,3 Carolin Daamen,3 Matthias Augustin5 1University of Southern California, Los Angeles, CA; 2The University of Manchester, Manchester, UK; 3Bristol Myers Squibb, Princeton, NJ; 4Evidera, Bethesda, MD; 5University Medical Center, Hamburg, Germany Presented at the Fall Clinical Dermatology Conference; October 20–23, 2022; Las Vegas, NV This poster may not be reproduced without written permission from the authors.Email for April Armstrong, MD, MPH: AprilArmstrong@post.harvard.edu Scientifi c Content on Demand To request a copy of this poster: Scan QR code via a barcode reader application QR codes are valid for 30 days after congress presentation date Synopsis • Patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs) and is approved by the US Food and Drug Administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • This systematic literature review (SLR) and network meta-analysis (NMA) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the Psoriasis Area and Severity Index (PASI) at Weeks 10−16, 24−28, and 44−60 • PASI 75 (75% improvement in PASI) response rate with deucravacitinib was comparable to that of first-generation biologics at Week 16, and higher at Week 24; at Week 52, it was comparable to that of the most effective fi rst- generation biologics Objective • The objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis Methods • Electronic databases were searched through October 2021 for RCTs of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on PASI • Phase 3 trial data were included when: — Nonresponder imputation was applied1,2 — Studies were conducted in multiple or single countries with diverse ethnic representation • NMA was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate PASI responses over short-, mid-, and long-term follow-up periods (Weeks 10−16, 24−28, and 44−60, respectively) and reported following the PRISMA Reporting Guidelines for meta-analysis3 Results • The SLR identifi ed 47 phase 3 RCTs that applied nonresponder imputation and were included in the NMA (Figure 1 and Figure 2A); the mid-term analysis included 28 studies (Figure 2B); the long-term analysis included 21 studies (Figure 2C) Figure 1. PRISMA flow diagram Full-text articles excluded (n = 446) • Duplicates (n = 11) • Publication type not of interest (n = 17) • Study design not of interest (n = 25) • Population not of interest (n = 60) • Intervention/comparator not of interest (n = 105) • Outcomes not of interest (n = 189) • Relevant SLRs/NMAs published 2019-2020 (n = 39) Records excluded by title and abstract screening (n = 3632) Full-text articles assessed for eligibility (n = 818) 251 RCT publications and 132 pooleda analyses included in SLR Duplicates removed (n = 3037) RCTs included in global PASI NMA (n = 96 unique RCTs)b Records screened (n = 4450) RCTs included in phase 3 Global NRI PASI NMA (n = 47 unique RCTs)b Id e n ti fi ca ti o n Sc re e n in g E li gi b il it y In cl u d e d Records identified through database searching (n = 7487) Records identified through other sources (conference proceedings: n = 11) aPooled analyses of RCTs were not included in the SLR unless unique data were available that were not published elsewhere. bRCTs eligible for Global PASI NMA and phase 3 global NRI PASI NMA, including POETYK PS0-1 and POETYK PSO-2. NMA, network meta-analysis; NRI, nonresponder imputation; PASI, Psoriasis Area and Severity Index; RCT, randomized controlled trial; SLR, systematic literature review. Figure 2. Network plots of trials included in the short- term (10–16 weeks; A), mid-term (24–28 weeks; B), and long-term (44–60 weeks; C) analyses v ETANERCEPT STUDY GROUP LIBERATE ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP FIXTURE M10-114 M10-315 OPT COMPARE STUDY reSURFACE 2 UNCOVER 2, 3 LIBERATE ESTEEM 1, 2 LIBERATE POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 2, 3 UNCOVER 1, 2, 3 ERASURE FEATURE FIXTURE JUNCTURE ALLURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMerge BE VIVID BE RADIANT BE READY BE VIVID ORION VOYAGE 1, 2 VOYAGE 1, 2 BE SURE IMMvent VOYAGE 1, 2 REVEAL CHAMPION EXPRESS EXPRESS II SPIRIT RESTORE 1 reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 1, 2 reSURFACE 2 ACCEPT UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE Reich, 2020 CHAMPION CHAMPION METOP ECLIPSE Blauvelt, 2021 IMMhance UltiMMa-1, -2 UltiMMa-1, -2 IXORA-5 ERASURE FEATURE FIXTURE JUNCTURE A. ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 UltiMMa-1, -2 UltiMMa-1, -2 POETYK 1 UNCOVER 3 AMAGINE 2, 3 AMAGINE 2, 3 IMMerge BE RADIANT VOYAGE 1 VOYAGE 1 VOYAGE 1 EXPRESS EXPRESS II FIXTURE FIXTUREFIXTURE METOP ECLIPSEIXORA-5 IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO LIBERATE CLEAR C. ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP ESTEEM 1, 2 POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 3 ERASURE FEATURE FIXTURE ERASURE FEATURE FIXTURE ALLURE ERASURE FEATURE FIXTURE AMAGINE 2, 3 BE VIVID AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMhance IMMerge BE RADIANT ORION VOYAGE 1, 2 VOYAGE 1, 2 VOYAGE 1, 2 BE SURE EXPRESS EXPRESS II reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 2 UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE METOP ECLIPSE IXORA-5 reSURFACE 1, 2 B. ETANERCEPT STUDY GROUP FIXTURE reSURFACE 2 ACT, acitretin; ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IXE, ixekizumab; MTX, methotrexate; PBO, placebo; RIS, risankizumab; Q2W, once every 2 weeks; SEC, secukinumab; TIL, tildrakizumab; UST, ustekinumab. • PASI 75 response rate with deucravacitinib at Week 16 (54.1%; credible interval [Crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [Crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [Crl, 74.0%, 83.5%] for infl iximab; Figure 3A) • PASI 75 response with deucravacitinib increased at Week 24 to 63.3% (Crl, 58.0%, 68.4%; Figure 3B) • At Week 52, the PASI 75 response rate for deucravacitinib (65.9%; Crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; Crl, 55.3%, 69.6%) and ustekinumab (68.0%; Crl, 64.6%, 71.5%; Figure 3C) • Newer IL-17 and IL-23 inhibitors showed the highest PASI 75 response rates of the included treatments, across all time points Figure 3. Short-term estimated PASI 75 response,a posterior median and 95% CrI. Weeks 10–16 (A), mid- term estimated PASI 75 response for Weeks 24–28 (B), and long-term estimated PASI 75 response for Weeks 44–60 (C) 56.7 IFX 5 mg/kg ADM 40 mg 62.8 48.4 APR 30 mg 45.0 MTX UST 90 mg 70.9 UST 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W BIM 320b mg TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 First-generation biologics Second-generation biologics A. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 PBO DEUC 6 mg ETC 50 mg BIW UST 45 or 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL–12/23 Anti–IL-17 Anti–IL-23 C. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg UST 45 or 90 mg UST 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti–TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 B. 74.675.074.271.0 72.3 72.2 73.4 First-generation biologics Second-generation biologics First-generation biologics Second-generation biologics aAdjusted for placebo response rates. bBIM is not approved for use in the United States. Note: posterior median value given for each therapy; error bars represent 95% CrI. ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; CrI, credible interval; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IL, interleukin; IXE, ixekizumab; MTX, methotrexate; NMA, network meta-analysis; PASI, Psoriasis Area and Severity Index; PBO, placebo; Q2W, once every 2 weeks; Q4W, once every 4 weeks; Q8W, once every 8 weeks; RIS, risankizumab; SEC, secukinumab; TIL, tildrakizumab; TNF, tumor necrosis factor; UST, ustekinumab. Conclusions • Among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • The PASI 75 response rates for deucravacitinib were within the range of those for first-generation biologics at Weeks 10–16 and 24–28 • At 1 year, the PASI 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • The psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies References 1. Guideline on Missing Data in Confirmatory Clinical Trials. European Medicines Agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. Guidance for Sponsors, Clinical Investigators, and IRBs. US Food and Drug Administration; 2008. http://www.fda.gov/downloads/ RegulatoryInformation/Guidances/ucm126489.pdf 3. Page MJ, et al. PLoS Med. 2021;18:e1003583. Acknowledgments • This study was sponsored by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Cheryl Jones of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AA: Grants and personal fees: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis; Personal fees: Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant; Grants: Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work • RBW: Research grants: AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB; Consulting fees: AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DiCE, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and UNION • YZ, JZ, RK, and CD: Employees of and may own stock options in Bristol Myers Squibb • AC, AK, DJ, and TW: Employed by Evidera, a company that provides consulting and other research services to Bristol Myers Squibb • MA: Advisory boards: AbbVie, Amgen, Boehringer Ingelheim, Janssen Biotech, and Leo Pharma; Consulting fees: AbbVie, Amgen, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Honoraria: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Investigator: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Leo Pharma, Merck, Novartis, Sun Pharma, and UCB; Research grants: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Janssen Biotech, Leo Pharma, Merck, and Sun Pharma; Speaker: AbbVie, Amgen, Janssen Biotech, Leo Pharma, Sun Pharma, and UCB Indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis April Armstrong,1 Richard B. Warren,2 Yichen Zhong,3 Joe Zhuo,3 Allie Cichewicz,4 Ananth Kadambi,4 Daniela R. Junqueira,4 Tracy Westley,4 Renata Kisa,3 Carolin Daamen,3 Matthias Augustin5 1University of Southern California, Los Angeles, CA; 2The University of Manchester, Manchester, UK; 3Bristol Myers Squibb, Princeton, NJ; 4Evidera, Bethesda, MD; 5University Medical Center, Hamburg, Germany Presented at the Fall Clinical Dermatology Conference; October 20–23, 2022; Las Vegas, NV This poster may not be reproduced without written permission from the authors.Email for April Armstrong, MD, MPH: AprilArmstrong@post.harvard.edu Scientifi c Content on Demand To request a copy of this poster: Scan QR code via a barcode reader application QR codes are valid for 30 days after congress presentation date Synopsis • Patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs) and is approved by the US Food and Drug Administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • This systematic literature review (SLR) and network meta-analysis (NMA) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the Psoriasis Area and Severity Index (PASI) at Weeks 10−16, 24−28, and 44−60 • PASI 75 (75% improvement in PASI) response rate with deucravacitinib was comparable to that of first-generation biologics at Week 16, and higher at Week 24; at Week 52, it was comparable to that of the most effective fi rst- generation biologics Objective • The objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis Methods • Electronic databases were searched through October 2021 for RCTs of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on PASI • Phase 3 trial data were included when: — Nonresponder imputation was applied1,2 — Studies were conducted in multiple or single countries with diverse ethnic representation • NMA was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate PASI responses over short-, mid-, and long-term follow-up periods (Weeks 10−16, 24−28, and 44−60, respectively) and reported following the PRISMA Reporting Guidelines for meta-analysis3 Results • The SLR identifi ed 47 phase 3 RCTs that applied nonresponder imputation and were included in the NMA (Figure 1 and Figure 2A); the mid-term analysis included 28 studies (Figure 2B); the long-term analysis included 21 studies (Figure 2C) Figure 1. PRISMA flow diagram Full-text articles excluded (n = 446) • Duplicates (n = 11) • Publication type not of interest (n = 17) • Study design not of interest (n = 25) • Population not of interest (n = 60) • Intervention/comparator not of interest (n = 105) • Outcomes not of interest (n = 189) • Relevant SLRs/NMAs published 2019-2020 (n = 39) Records excluded by title and abstract screening (n = 3632) Full-text articles assessed for eligibility (n = 818) 251 RCT publications and 132 pooleda analyses included in SLR Duplicates removed (n = 3037) RCTs included in global PASI NMA (n = 96 unique RCTs)b Records screened (n = 4450) RCTs included in phase 3 Global NRI PASI NMA (n = 47 unique RCTs)b Id e n ti fi ca ti o n Sc re e n in g E li gi b il it y In cl u d e d Records identified through database searching (n = 7487) Records identified through other sources (conference proceedings: n = 11) aPooled analyses of RCTs were not included in the SLR unless unique data were available that were not published elsewhere. bRCTs eligible for Global PASI NMA and phase 3 global NRI PASI NMA, including POETYK PS0-1 and POETYK PSO-2. NMA, network meta-analysis; NRI, nonresponder imputation; PASI, Psoriasis Area and Severity Index; RCT, randomized controlled trial; SLR, systematic literature review. Figure 2. Network plots of trials included in the short- term (10–16 weeks; A), mid-term (24–28 weeks; B), and long-term (44–60 weeks; C) analyses v ETANERCEPT STUDY GROUP LIBERATE ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP FIXTURE M10-114 M10-315 OPT COMPARE STUDY reSURFACE 2 UNCOVER 2, 3 LIBERATE ESTEEM 1, 2 LIBERATE POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 2, 3 UNCOVER 1, 2, 3 ERASURE FEATURE FIXTURE JUNCTURE ALLURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMerge BE VIVID BE RADIANT BE READY BE VIVID ORION VOYAGE 1, 2 VOYAGE 1, 2 BE SURE IMMvent VOYAGE 1, 2 REVEAL CHAMPION EXPRESS EXPRESS II SPIRIT RESTORE 1 reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 1, 2 reSURFACE 2 ACCEPT UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE Reich, 2020 CHAMPION CHAMPION METOP ECLIPSE Blauvelt, 2021 IMMhance UltiMMa-1, -2 UltiMMa-1, -2 IXORA-5 ERASURE FEATURE FIXTURE JUNCTURE A. ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 UltiMMa-1, -2 UltiMMa-1, -2 POETYK 1 UNCOVER 3 AMAGINE 2, 3 AMAGINE 2, 3 IMMerge BE RADIANT VOYAGE 1 VOYAGE 1 VOYAGE 1 EXPRESS EXPRESS II FIXTURE FIXTUREFIXTURE METOP ECLIPSEIXORA-5 IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO LIBERATE CLEAR C. ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP ESTEEM 1, 2 POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 3 ERASURE FEATURE FIXTURE ERASURE FEATURE FIXTURE ALLURE ERASURE FEATURE FIXTURE AMAGINE 2, 3 BE VIVID AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMhance IMMerge BE RADIANT ORION VOYAGE 1, 2 VOYAGE 1, 2 VOYAGE 1, 2 BE SURE EXPRESS EXPRESS II reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 2 UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE METOP ECLIPSE IXORA-5 reSURFACE 1, 2 B. ETANERCEPT STUDY GROUP FIXTURE reSURFACE 2 ACT, acitretin; ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IXE, ixekizumab; MTX, methotrexate; PBO, placebo; RIS, risankizumab; Q2W, once every 2 weeks; SEC, secukinumab; TIL, tildrakizumab; UST, ustekinumab. • PASI 75 response rate with deucravacitinib at Week 16 (54.1%; credible interval [Crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [Crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [Crl, 74.0%, 83.5%] for infl iximab; Figure 3A) • PASI 75 response with deucravacitinib increased at Week 24 to 63.3% (Crl, 58.0%, 68.4%; Figure 3B) • At Week 52, the PASI 75 response rate for deucravacitinib (65.9%; Crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; Crl, 55.3%, 69.6%) and ustekinumab (68.0%; Crl, 64.6%, 71.5%; Figure 3C) • Newer IL-17 and IL-23 inhibitors showed the highest PASI 75 response rates of the included treatments, across all time points Figure 3. Short-term estimated PASI 75 response,a posterior median and 95% CrI. Weeks 10–16 (A), mid- term estimated PASI 75 response for Weeks 24–28 (B), and long-term estimated PASI 75 response for Weeks 44–60 (C) 56.7 IFX 5 mg/kg ADM 40 mg 62.8 48.4 APR 30 mg 45.0 MTX UST 90 mg 70.9 UST 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W BIM 320b mg TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 First-generation biologics Second-generation biologics A. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 PBO DEUC 6 mg ETC 50 mg BIW UST 45 or 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL–12/23 Anti–IL-17 Anti–IL-23 C. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg UST 45 or 90 mg UST 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti–TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 B. 74.675.074.271.0 72.3 72.2 73.4 First-generation biologics Second-generation biologics First-generation biologics Second-generation biologics aAdjusted for placebo response rates. bBIM is not approved for use in the United States. Note: posterior median value given for each therapy; error bars represent 95% CrI. ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; CrI, credible interval; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IL, interleukin; IXE, ixekizumab; MTX, methotrexate; NMA, network meta-analysis; PASI, Psoriasis Area and Severity Index; PBO, placebo; Q2W, once every 2 weeks; Q4W, once every 4 weeks; Q8W, once every 8 weeks; RIS, risankizumab; SEC, secukinumab; TIL, tildrakizumab; TNF, tumor necrosis factor; UST, ustekinumab. Conclusions • Among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • The PASI 75 response rates for deucravacitinib were within the range of those for first-generation biologics at Weeks 10–16 and 24–28 • At 1 year, the PASI 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • The psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies References 1. Guideline on Missing Data in Confirmatory Clinical Trials. European Medicines Agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. Guidance for Sponsors, Clinical Investigators, and IRBs. US Food and Drug Administration; 2008. http://www.fda.gov/downloads/ RegulatoryInformation/Guidances/ucm126489.pdf 3. Page MJ, et al. PLoS Med. 2021;18:e1003583. Acknowledgments • This study was sponsored by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Cheryl Jones of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AA: Grants and personal fees: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis; Personal fees: Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant; Grants: Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work • RBW: Research grants: AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB; Consulting fees: AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DiCE, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and UNION • YZ, JZ, RK, and CD: Employees of and may own stock options in Bristol Myers Squibb • AC, AK, DJ, and TW: Employed by Evidera, a company that provides consulting and other research services to Bristol Myers Squibb • MA: Advisory boards: AbbVie, Amgen, Boehringer Ingelheim, Janssen Biotech, and Leo Pharma; Consulting fees: AbbVie, Amgen, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Honoraria: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Investigator: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Leo Pharma, Merck, Novartis, Sun Pharma, and UCB; Research grants: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Janssen Biotech, Leo Pharma, Merck, and Sun Pharma; Speaker: AbbVie, Amgen, Janssen Biotech, Leo Pharma, Sun Pharma, and UCB Indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis April Armstrong,1 Richard B. Warren,2 Yichen Zhong,3 Joe Zhuo,3 Allie Cichewicz,4 Ananth Kadambi,4 Daniela R. Junqueira,4 Tracy Westley,4 Renata Kisa,3 Carolin Daamen,3 Matthias Augustin5 1University of Southern California, Los Angeles, CA; 2The University of Manchester, Manchester, UK; 3Bristol Myers Squibb, Princeton, NJ; 4Evidera, Bethesda, MD; 5University Medical Center, Hamburg, Germany Presented at the Fall Clinical Dermatology Conference; October 20–23, 2022; Las Vegas, NV This poster may not be reproduced without written permission from the authors.Email for April Armstrong, MD, MPH: AprilArmstrong@post.harvard.edu Scientifi c Content on Demand To request a copy of this poster: Scan QR code via a barcode reader application QR codes are valid for 30 days after congress presentation date Synopsis • Patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs) and is approved by the US Food and Drug Administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • This systematic literature review (SLR) and network meta-analysis (NMA) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the Psoriasis Area and Severity Index (PASI) at Weeks 10−16, 24−28, and 44−60 • PASI 75 (75% improvement in PASI) response rate with deucravacitinib was comparable to that of first-generation biologics at Week 16, and higher at Week 24; at Week 52, it was comparable to that of the most effective fi rst- generation biologics Objective • The objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis Methods • Electronic databases were searched through October 2021 for RCTs of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on PASI • Phase 3 trial data were included when: — Nonresponder imputation was applied1,2 — Studies were conducted in multiple or single countries with diverse ethnic representation • NMA was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate PASI responses over short-, mid-, and long-term follow-up periods (Weeks 10−16, 24−28, and 44−60, respectively) and reported following the PRISMA Reporting Guidelines for meta-analysis3 Results • The SLR identifi ed 47 phase 3 RCTs that applied nonresponder imputation and were included in the NMA (Figure 1 and Figure 2A); the mid-term analysis included 28 studies (Figure 2B); the long-term analysis included 21 studies (Figure 2C) Figure 1. PRISMA flow diagram Full-text articles excluded (n = 446) • Duplicates (n = 11) • Publication type not of interest (n = 17) • Study design not of interest (n = 25) • Population not of interest (n = 60) • Intervention/comparator not of interest (n = 105) • Outcomes not of interest (n = 189) • Relevant SLRs/NMAs published 2019-2020 (n = 39) Records excluded by title and abstract screening (n = 3632) Full-text articles assessed for eligibility (n = 818) 251 RCT publications and 132 pooleda analyses included in SLR Duplicates removed (n = 3037) RCTs included in global PASI NMA (n = 96 unique RCTs)b Records screened (n = 4450) RCTs included in phase 3 Global NRI PASI NMA (n = 47 unique RCTs)b Id e n ti fi ca ti o n Sc re e n in g E li gi b il it y In cl u d e d Records identified through database searching (n = 7487) Records identified through other sources (conference proceedings: n = 11) aPooled analyses of RCTs were not included in the SLR unless unique data were available that were not published elsewhere. bRCTs eligible for Global PASI NMA and phase 3 global NRI PASI NMA, including POETYK PS0-1 and POETYK PSO-2. NMA, network meta-analysis; NRI, nonresponder imputation; PASI, Psoriasis Area and Severity Index; RCT, randomized controlled trial; SLR, systematic literature review. Figure 2. Network plots of trials included in the short- term (10–16 weeks; A), mid-term (24–28 weeks; B), and long-term (44–60 weeks; C) analyses v ETANERCEPT STUDY GROUP LIBERATE ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP FIXTURE M10-114 M10-315 OPT COMPARE STUDY reSURFACE 2 UNCOVER 2, 3 LIBERATE ESTEEM 1, 2 LIBERATE POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 2, 3 UNCOVER 1, 2, 3 ERASURE FEATURE FIXTURE JUNCTURE ALLURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMerge BE VIVID BE RADIANT BE READY BE VIVID ORION VOYAGE 1, 2 VOYAGE 1, 2 BE SURE IMMvent VOYAGE 1, 2 REVEAL CHAMPION EXPRESS EXPRESS II SPIRIT RESTORE 1 reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 1, 2 reSURFACE 2 ACCEPT UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE Reich, 2020 CHAMPION CHAMPION METOP ECLIPSE Blauvelt, 2021 IMMhance UltiMMa-1, -2 UltiMMa-1, -2 IXORA-5 ERASURE FEATURE FIXTURE JUNCTURE A. ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 UltiMMa-1, -2 UltiMMa-1, -2 POETYK 1 UNCOVER 3 AMAGINE 2, 3 AMAGINE 2, 3 IMMerge BE RADIANT VOYAGE 1 VOYAGE 1 VOYAGE 1 EXPRESS EXPRESS II FIXTURE FIXTUREFIXTURE METOP ECLIPSEIXORA-5 IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO LIBERATE CLEAR C. ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP ESTEEM 1, 2 POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 3 ERASURE FEATURE FIXTURE ERASURE FEATURE FIXTURE ALLURE ERASURE FEATURE FIXTURE AMAGINE 2, 3 BE VIVID AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMhance IMMerge BE RADIANT ORION VOYAGE 1, 2 VOYAGE 1, 2 VOYAGE 1, 2 BE SURE EXPRESS EXPRESS II reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 2 UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE METOP ECLIPSE IXORA-5 reSURFACE 1, 2 B. ETANERCEPT STUDY GROUP FIXTURE reSURFACE 2 ACT, acitretin; ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IXE, ixekizumab; MTX, methotrexate; PBO, placebo; RIS, risankizumab; Q2W, once every 2 weeks; SEC, secukinumab; TIL, tildrakizumab; UST, ustekinumab. • PASI 75 response rate with deucravacitinib at Week 16 (54.1%; credible interval [Crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [Crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [Crl, 74.0%, 83.5%] for infl iximab; Figure 3A) • PASI 75 response with deucravacitinib increased at Week 24 to 63.3% (Crl, 58.0%, 68.4%; Figure 3B) • At Week 52, the PASI 75 response rate for deucravacitinib (65.9%; Crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; Crl, 55.3%, 69.6%) and ustekinumab (68.0%; Crl, 64.6%, 71.5%; Figure 3C) • Newer IL-17 and IL-23 inhibitors showed the highest PASI 75 response rates of the included treatments, across all time points Figure 3. Short-term estimated PASI 75 response,a posterior median and 95% CrI. Weeks 10–16 (A), mid- term estimated PASI 75 response for Weeks 24–28 (B), and long-term estimated PASI 75 response for Weeks 44–60 (C) 56.7 IFX 5 mg/kg ADM 40 mg 62.8 48.4 APR 30 mg 45.0 MTX UST 90 mg 70.9 UST 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W BIM 320b mg TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 First-generation biologics Second-generation biologics A. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 PBO DEUC 6 mg ETC 50 mg BIW UST 45 or 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL–12/23 Anti–IL-17 Anti–IL-23 C. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg UST 45 or 90 mg UST 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti–TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 B. 74.675.074.271.0 72.3 72.2 73.4 First-generation biologics Second-generation biologics First-generation biologics Second-generation biologics aAdjusted for placebo response rates. bBIM is not approved for use in the United States. Note: posterior median value given for each therapy; error bars represent 95% CrI. ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; CrI, credible interval; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IL, interleukin; IXE, ixekizumab; MTX, methotrexate; NMA, network meta-analysis; PASI, Psoriasis Area and Severity Index; PBO, placebo; Q2W, once every 2 weeks; Q4W, once every 4 weeks; Q8W, once every 8 weeks; RIS, risankizumab; SEC, secukinumab; TIL, tildrakizumab; TNF, tumor necrosis factor; UST, ustekinumab. Conclusions • Among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • The PASI 75 response rates for deucravacitinib were within the range of those for first-generation biologics at Weeks 10–16 and 24–28 • At 1 year, the PASI 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • The psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies References 1. Guideline on Missing Data in Confirmatory Clinical Trials. European Medicines Agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. Guidance for Sponsors, Clinical Investigators, and IRBs. US Food and Drug Administration; 2008. http://www.fda.gov/downloads/ RegulatoryInformation/Guidances/ucm126489.pdf 3. Page MJ, et al. PLoS Med. 2021;18:e1003583. Acknowledgments • This study was sponsored by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Cheryl Jones of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AA: Grants and personal fees: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis; Personal fees: Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant; Grants: Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work • RBW: Research grants: AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB; Consulting fees: AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DiCE, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and UNION • YZ, JZ, RK, and CD: Employees of and may own stock options in Bristol Myers Squibb • AC, AK, DJ, and TW: Employed by Evidera, a company that provides consulting and other research services to Bristol Myers Squibb • MA: Advisory boards: AbbVie, Amgen, Boehringer Ingelheim, Janssen Biotech, and Leo Pharma; Consulting fees: AbbVie, Amgen, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Honoraria: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Investigator: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Leo Pharma, Merck, Novartis, Sun Pharma, and UCB; Research grants: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Janssen Biotech, Leo Pharma, Merck, and Sun Pharma; Speaker: AbbVie, Amgen, Janssen Biotech, Leo Pharma, Sun Pharma, and UCB Indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis April Armstrong,1 Richard B. Warren,2 Yichen Zhong,3 Joe Zhuo,3 Allie Cichewicz,4 Ananth Kadambi,4 Daniela R. Junqueira,4 Tracy Westley,4 Renata Kisa,3 Carolin Daamen,3 Matthias Augustin5 1University of Southern California, Los Angeles, CA; 2The University of Manchester, Manchester, UK; 3Bristol Myers Squibb, Princeton, NJ; 4Evidera, Bethesda, MD; 5University Medical Center, Hamburg, Germany Presented at the Fall Clinical Dermatology Conference; October 20–23, 2022; Las Vegas, NV This poster may not be reproduced without written permission from the authors.Email for April Armstrong, MD, MPH: AprilArmstrong@post.harvard.edu Scientifi c Content on Demand To request a copy of this poster: Scan QR code via a barcode reader application QR codes are valid for 30 days after congress presentation date Synopsis • Patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs) and is approved by the US Food and Drug Administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • This systematic literature review (SLR) and network meta-analysis (NMA) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the Psoriasis Area and Severity Index (PASI) at Weeks 10−16, 24−28, and 44−60 • PASI 75 (75% improvement in PASI) response rate with deucravacitinib was comparable to that of first-generation biologics at Week 16, and higher at Week 24; at Week 52, it was comparable to that of the most effective fi rst- generation biologics Objective • The objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis Methods • Electronic databases were searched through October 2021 for RCTs of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on PASI • Phase 3 trial data were included when: — Nonresponder imputation was applied1,2 — Studies were conducted in multiple or single countries with diverse ethnic representation • NMA was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate PASI responses over short-, mid-, and long-term follow-up periods (Weeks 10−16, 24−28, and 44−60, respectively) and reported following the PRISMA Reporting Guidelines for meta-analysis3 Results • The SLR identifi ed 47 phase 3 RCTs that applied nonresponder imputation and were included in the NMA (Figure 1 and Figure 2A); the mid-term analysis included 28 studies (Figure 2B); the long-term analysis included 21 studies (Figure 2C) Figure 1. PRISMA flow diagram Full-text articles excluded (n = 446) • Duplicates (n = 11) • Publication type not of interest (n = 17) • Study design not of interest (n = 25) • Population not of interest (n = 60) • Intervention/comparator not of interest (n = 105) • Outcomes not of interest (n = 189) • Relevant SLRs/NMAs published 2019-2020 (n = 39) Records excluded by title and abstract screening (n = 3632) Full-text articles assessed for eligibility (n = 818) 251 RCT publications and 132 pooleda analyses included in SLR Duplicates removed (n = 3037) RCTs included in global PASI NMA (n = 96 unique RCTs)b Records screened (n = 4450) RCTs included in phase 3 Global NRI PASI NMA (n = 47 unique RCTs)b Id e n ti fi ca ti o n Sc re e n in g E li gi b il it y In cl u d e d Records identified through database searching (n = 7487) Records identified through other sources (conference proceedings: n = 11) aPooled analyses of RCTs were not included in the SLR unless unique data were available that were not published elsewhere. bRCTs eligible for Global PASI NMA and phase 3 global NRI PASI NMA, including POETYK PS0-1 and POETYK PSO-2. NMA, network meta-analysis; NRI, nonresponder imputation; PASI, Psoriasis Area and Severity Index; RCT, randomized controlled trial; SLR, systematic literature review. Figure 2. Network plots of trials included in the short- term (10–16 weeks; A), mid-term (24–28 weeks; B), and long-term (44–60 weeks; C) analyses v ETANERCEPT STUDY GROUP LIBERATE ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP FIXTURE M10-114 M10-315 OPT COMPARE STUDY reSURFACE 2 UNCOVER 2, 3 LIBERATE ESTEEM 1, 2 LIBERATE POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 2, 3 UNCOVER 1, 2, 3 ERASURE FEATURE FIXTURE JUNCTURE ALLURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMerge BE VIVID BE RADIANT BE READY BE VIVID ORION VOYAGE 1, 2 VOYAGE 1, 2 BE SURE IMMvent VOYAGE 1, 2 REVEAL CHAMPION EXPRESS EXPRESS II SPIRIT RESTORE 1 reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 1, 2 reSURFACE 2 ACCEPT UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE Reich, 2020 CHAMPION CHAMPION METOP ECLIPSE Blauvelt, 2021 IMMhance UltiMMa-1, -2 UltiMMa-1, -2 IXORA-5 ERASURE FEATURE FIXTURE JUNCTURE A. ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 UltiMMa-1, -2 UltiMMa-1, -2 POETYK 1 UNCOVER 3 AMAGINE 2, 3 AMAGINE 2, 3 IMMerge BE RADIANT VOYAGE 1 VOYAGE 1 VOYAGE 1 EXPRESS EXPRESS II FIXTURE FIXTUREFIXTURE METOP ECLIPSEIXORA-5 IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO LIBERATE CLEAR C. ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP ESTEEM 1, 2 POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 3 ERASURE FEATURE FIXTURE ERASURE FEATURE FIXTURE ALLURE ERASURE FEATURE FIXTURE AMAGINE 2, 3 BE VIVID AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMhance IMMerge BE RADIANT ORION VOYAGE 1, 2 VOYAGE 1, 2 VOYAGE 1, 2 BE SURE EXPRESS EXPRESS II reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 2 UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE METOP ECLIPSE IXORA-5 reSURFACE 1, 2 B. ETANERCEPT STUDY GROUP FIXTURE reSURFACE 2 ACT, acitretin; ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IXE, ixekizumab; MTX, methotrexate; PBO, placebo; RIS, risankizumab; Q2W, once every 2 weeks; SEC, secukinumab; TIL, tildrakizumab; UST, ustekinumab. • PASI 75 response rate with deucravacitinib at Week 16 (54.1%; credible interval [Crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [Crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [Crl, 74.0%, 83.5%] for infl iximab; Figure 3A) • PASI 75 response with deucravacitinib increased at Week 24 to 63.3% (Crl, 58.0%, 68.4%; Figure 3B) • At Week 52, the PASI 75 response rate for deucravacitinib (65.9%; Crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; Crl, 55.3%, 69.6%) and ustekinumab (68.0%; Crl, 64.6%, 71.5%; Figure 3C) • Newer IL-17 and IL-23 inhibitors showed the highest PASI 75 response rates of the included treatments, across all time points Figure 3. Short-term estimated PASI 75 response,a posterior median and 95% CrI. Weeks 10–16 (A), mid- term estimated PASI 75 response for Weeks 24–28 (B), and long-term estimated PASI 75 response for Weeks 44–60 (C) 56.7 IFX 5 mg/kg ADM 40 mg 62.8 48.4 APR 30 mg 45.0 MTX UST 90 mg 70.9 UST 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W BIM 320b mg TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 First-generation biologics Second-generation biologics A. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 PBO DEUC 6 mg ETC 50 mg BIW UST 45 or 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL–12/23 Anti–IL-17 Anti–IL-23 C. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg UST 45 or 90 mg UST 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti–TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 B. 74.675.074.271.0 72.3 72.2 73.4 First-generation biologics Second-generation biologics First-generation biologics Second-generation biologics aAdjusted for placebo response rates. bBIM is not approved for use in the United States. Note: posterior median value given for each therapy; error bars represent 95% CrI. ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; CrI, credible interval; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IL, interleukin; IXE, ixekizumab; MTX, methotrexate; NMA, network meta-analysis; PASI, Psoriasis Area and Severity Index; PBO, placebo; Q2W, once every 2 weeks; Q4W, once every 4 weeks; Q8W, once every 8 weeks; RIS, risankizumab; SEC, secukinumab; TIL, tildrakizumab; TNF, tumor necrosis factor; UST, ustekinumab. Conclusions • Among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • The PASI 75 response rates for deucravacitinib were within the range of those for first-generation biologics at Weeks 10–16 and 24–28 • At 1 year, the PASI 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • The psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies References 1. Guideline on Missing Data in Confirmatory Clinical Trials. European Medicines Agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. Guidance for Sponsors, Clinical Investigators, and IRBs. US Food and Drug Administration; 2008. http://www.fda.gov/downloads/ RegulatoryInformation/Guidances/ucm126489.pdf 3. Page MJ, et al. PLoS Med. 2021;18:e1003583. Acknowledgments • This study was sponsored by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Cheryl Jones of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AA: Grants and personal fees: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis; Personal fees: Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant; Grants: Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work • RBW: Research grants: AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB; Consulting fees: AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DiCE, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and UNION • YZ, JZ, RK, and CD: Employees of and may own stock options in Bristol Myers Squibb • AC, AK, DJ, and TW: Employed by Evidera, a company that provides consulting and other research services to Bristol Myers Squibb • MA: Advisory boards: AbbVie, Amgen, Boehringer Ingelheim, Janssen Biotech, and Leo Pharma; Consulting fees: AbbVie, Amgen, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Honoraria: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Investigator: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Leo Pharma, Merck, Novartis, Sun Pharma, and UCB; Research grants: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Janssen Biotech, Leo Pharma, Merck, and Sun Pharma; Speaker: AbbVie, Amgen, Janssen Biotech, Leo Pharma, Sun Pharma, and UCB Indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis April Armstrong,1 Richard B. Warren,2 Yichen Zhong,3 Joe Zhuo,3 Allie Cichewicz,4 Ananth Kadambi,4 Daniela R. Junqueira,4 Tracy Westley,4 Renata Kisa,3 Carolin Daamen,3 Matthias Augustin5 1University of Southern California, Los Angeles, CA; 2The University of Manchester, Manchester, UK; 3Bristol Myers Squibb, Princeton, NJ; 4Evidera, Bethesda, MD; 5University Medical Center, Hamburg, Germany Presented at the Fall Clinical Dermatology Conference; October 20–23, 2022; Las Vegas, NV This poster may not be reproduced without written permission from the authors.Email for April Armstrong, MD, MPH: AprilArmstrong@post.harvard.edu Scientifi c Content on Demand To request a copy of this poster: Scan QR code via a barcode reader application QR codes are valid for 30 days after congress presentation date Synopsis • Patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs) and is approved by the US Food and Drug Administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • This systematic literature review (SLR) and network meta-analysis (NMA) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the Psoriasis Area and Severity Index (PASI) at Weeks 10−16, 24−28, and 44−60 • PASI 75 (75% improvement in PASI) response rate with deucravacitinib was comparable to that of first-generation biologics at Week 16, and higher at Week 24; at Week 52, it was comparable to that of the most effective fi rst- generation biologics Objective • The objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis Methods • Electronic databases were searched through October 2021 for RCTs of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on PASI • Phase 3 trial data were included when: — Nonresponder imputation was applied1,2 — Studies were conducted in multiple or single countries with diverse ethnic representation • NMA was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate PASI responses over short-, mid-, and long-term follow-up periods (Weeks 10−16, 24−28, and 44−60, respectively) and reported following the PRISMA Reporting Guidelines for meta-analysis3 Results • The SLR identifi ed 47 phase 3 RCTs that applied nonresponder imputation and were included in the NMA (Figure 1 and Figure 2A); the mid-term analysis included 28 studies (Figure 2B); the long-term analysis included 21 studies (Figure 2C) Figure 1. PRISMA flow diagram Full-text articles excluded (n = 446) • Duplicates (n = 11) • Publication type not of interest (n = 17) • Study design not of interest (n = 25) • Population not of interest (n = 60) • Intervention/comparator not of interest (n = 105) • Outcomes not of interest (n = 189) • Relevant SLRs/NMAs published 2019-2020 (n = 39) Records excluded by title and abstract screening (n = 3632) Full-text articles assessed for eligibility (n = 818) 251 RCT publications and 132 pooleda analyses included in SLR Duplicates removed (n = 3037) RCTs included in global PASI NMA (n = 96 unique RCTs)b Records screened (n = 4450) RCTs included in phase 3 Global NRI PASI NMA (n = 47 unique RCTs)b Id e n ti fi ca ti o n Sc re e n in g E li gi b il it y In cl u d e d Records identified through database searching (n = 7487) Records identified through other sources (conference proceedings: n = 11) aPooled analyses of RCTs were not included in the SLR unless unique data were available that were not published elsewhere. bRCTs eligible for Global PASI NMA and phase 3 global NRI PASI NMA, including POETYK PS0-1 and POETYK PSO-2. NMA, network meta-analysis; NRI, nonresponder imputation; PASI, Psoriasis Area and Severity Index; RCT, randomized controlled trial; SLR, systematic literature review. Figure 2. Network plots of trials included in the short- term (10–16 weeks; A), mid-term (24–28 weeks; B), and long-term (44–60 weeks; C) analyses v ETANERCEPT STUDY GROUP LIBERATE ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP FIXTURE M10-114 M10-315 OPT COMPARE STUDY reSURFACE 2 UNCOVER 2, 3 LIBERATE ESTEEM 1, 2 LIBERATE POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 2, 3 UNCOVER 1, 2, 3 ERASURE FEATURE FIXTURE JUNCTURE ALLURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMerge BE VIVID BE RADIANT BE READY BE VIVID ORION VOYAGE 1, 2 VOYAGE 1, 2 BE SURE IMMvent VOYAGE 1, 2 REVEAL CHAMPION EXPRESS EXPRESS II SPIRIT RESTORE 1 reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 1, 2 reSURFACE 2 ACCEPT UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE Reich, 2020 CHAMPION CHAMPION METOP ECLIPSE Blauvelt, 2021 IMMhance UltiMMa-1, -2 UltiMMa-1, -2 IXORA-5 ERASURE FEATURE FIXTURE JUNCTURE A. ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 UltiMMa-1, -2 UltiMMa-1, -2 POETYK 1 UNCOVER 3 AMAGINE 2, 3 AMAGINE 2, 3 IMMerge BE RADIANT VOYAGE 1 VOYAGE 1 VOYAGE 1 EXPRESS EXPRESS II FIXTURE FIXTUREFIXTURE METOP ECLIPSEIXORA-5 IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO LIBERATE CLEAR C. ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP ESTEEM 1, 2 POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 3 ERASURE FEATURE FIXTURE ERASURE FEATURE FIXTURE ALLURE ERASURE FEATURE FIXTURE AMAGINE 2, 3 BE VIVID AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMhance IMMerge BE RADIANT ORION VOYAGE 1, 2 VOYAGE 1, 2 VOYAGE 1, 2 BE SURE EXPRESS EXPRESS II reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 2 UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE METOP ECLIPSE IXORA-5 reSURFACE 1, 2 B. ETANERCEPT STUDY GROUP FIXTURE reSURFACE 2 ACT, acitretin; ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IXE, ixekizumab; MTX, methotrexate; PBO, placebo; RIS, risankizumab; Q2W, once every 2 weeks; SEC, secukinumab; TIL, tildrakizumab; UST, ustekinumab. • PASI 75 response rate with deucravacitinib at Week 16 (54.1%; credible interval [Crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [Crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [Crl, 74.0%, 83.5%] for infl iximab; Figure 3A) • PASI 75 response with deucravacitinib increased at Week 24 to 63.3% (Crl, 58.0%, 68.4%; Figure 3B) • At Week 52, the PASI 75 response rate for deucravacitinib (65.9%; Crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; Crl, 55.3%, 69.6%) and ustekinumab (68.0%; Crl, 64.6%, 71.5%; Figure 3C) • Newer IL-17 and IL-23 inhibitors showed the highest PASI 75 response rates of the included treatments, across all time points Figure 3. Short-term estimated PASI 75 response,a posterior median and 95% CrI. Weeks 10–16 (A), mid- term estimated PASI 75 response for Weeks 24–28 (B), and long-term estimated PASI 75 response for Weeks 44–60 (C) 56.7 IFX 5 mg/kg ADM 40 mg 62.8 48.4 APR 30 mg 45.0 MTX UST 90 mg 70.9 UST 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W BIM 320b mg TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 First-generation biologics Second-generation biologics A. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 PBO DEUC 6 mg ETC 50 mg BIW UST 45 or 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL–12/23 Anti–IL-17 Anti–IL-23 C. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg UST 45 or 90 mg UST 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti–TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 B. 74.675.074.271.0 72.3 72.2 73.4 First-generation biologics Second-generation biologics First-generation biologics Second-generation biologics aAdjusted for placebo response rates. bBIM is not approved for use in the United States. Note: posterior median value given for each therapy; error bars represent 95% CrI. ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; CrI, credible interval; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IL, interleukin; IXE, ixekizumab; MTX, methotrexate; NMA, network meta-analysis; PASI, Psoriasis Area and Severity Index; PBO, placebo; Q2W, once every 2 weeks; Q4W, once every 4 weeks; Q8W, once every 8 weeks; RIS, risankizumab; SEC, secukinumab; TIL, tildrakizumab; TNF, tumor necrosis factor; UST, ustekinumab. Conclusions • Among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • The PASI 75 response rates for deucravacitinib were within the range of those for first-generation biologics at Weeks 10–16 and 24–28 • At 1 year, the PASI 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • The psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies References 1. Guideline on Missing Data in Confirmatory Clinical Trials. European Medicines Agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. Guidance for Sponsors, Clinical Investigators, and IRBs. US Food and Drug Administration; 2008. http://www.fda.gov/downloads/ RegulatoryInformation/Guidances/ucm126489.pdf 3. Page MJ, et al. PLoS Med. 2021;18:e1003583. Acknowledgments • This study was sponsored by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Cheryl Jones of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AA: Grants and personal fees: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis; Personal fees: Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant; Grants: Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work • RBW: Research grants: AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB; Consulting fees: AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DiCE, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and UNION • YZ, JZ, RK, and CD: Employees of and may own stock options in Bristol Myers Squibb • AC, AK, DJ, and TW: Employed by Evidera, a company that provides consulting and other research services to Bristol Myers Squibb • MA: Advisory boards: AbbVie, Amgen, Boehringer Ingelheim, Janssen Biotech, and Leo Pharma; Consulting fees: AbbVie, Amgen, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Honoraria: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Investigator: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Leo Pharma, Merck, Novartis, Sun Pharma, and UCB; Research grants: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Janssen Biotech, Leo Pharma, Merck, and Sun Pharma; Speaker: AbbVie, Amgen, Janssen Biotech, Leo Pharma, Sun Pharma, and UCB Indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis April Armstrong,1 Richard B. Warren,2 Yichen Zhong,3 Joe Zhuo,3 Allie Cichewicz,4 Ananth Kadambi,4 Daniela R. Junqueira,4 Tracy Westley,4 Renata Kisa,3 Carolin Daamen,3 Matthias Augustin5 1University of Southern California, Los Angeles, CA; 2The University of Manchester, Manchester, UK; 3Bristol Myers Squibb, Princeton, NJ; 4Evidera, Bethesda, MD; 5University Medical Center, Hamburg, Germany Presented at the Fall Clinical Dermatology Conference; October 20–23, 2022; Las Vegas, NV This poster may not be reproduced without written permission from the authors.Email for April Armstrong, MD, MPH: AprilArmstrong@post.harvard.edu Scientifi c Content on Demand To request a copy of this poster: Scan QR code via a barcode reader application QR codes are valid for 30 days after congress presentation date Synopsis • Patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs) and is approved by the US Food and Drug Administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • This systematic literature review (SLR) and network meta-analysis (NMA) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the Psoriasis Area and Severity Index (PASI) at Weeks 10−16, 24−28, and 44−60 • PASI 75 (75% improvement in PASI) response rate with deucravacitinib was comparable to that of first-generation biologics at Week 16, and higher at Week 24; at Week 52, it was comparable to that of the most effective fi rst- generation biologics Objective • The objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis Methods • Electronic databases were searched through October 2021 for RCTs of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on PASI • Phase 3 trial data were included when: — Nonresponder imputation was applied1,2 — Studies were conducted in multiple or single countries with diverse ethnic representation • NMA was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate PASI responses over short-, mid-, and long-term follow-up periods (Weeks 10−16, 24−28, and 44−60, respectively) and reported following the PRISMA Reporting Guidelines for meta-analysis3 Results • The SLR identifi ed 47 phase 3 RCTs that applied nonresponder imputation and were included in the NMA (Figure 1 and Figure 2A); the mid-term analysis included 28 studies (Figure 2B); the long-term analysis included 21 studies (Figure 2C) Figure 1. PRISMA flow diagram Full-text articles excluded (n = 446) • Duplicates (n = 11) • Publication type not of interest (n = 17) • Study design not of interest (n = 25) • Population not of interest (n = 60) • Intervention/comparator not of interest (n = 105) • Outcomes not of interest (n = 189) • Relevant SLRs/NMAs published 2019-2020 (n = 39) Records excluded by title and abstract screening (n = 3632) Full-text articles assessed for eligibility (n = 818) 251 RCT publications and 132 pooleda analyses included in SLR Duplicates removed (n = 3037) RCTs included in global PASI NMA (n = 96 unique RCTs)b Records screened (n = 4450) RCTs included in phase 3 Global NRI PASI NMA (n = 47 unique RCTs)b Id e n ti fi ca ti o n Sc re e n in g E li gi b il it y In cl u d e d Records identified through database searching (n = 7487) Records identified through other sources (conference proceedings: n = 11) aPooled analyses of RCTs were not included in the SLR unless unique data were available that were not published elsewhere. bRCTs eligible for Global PASI NMA and phase 3 global NRI PASI NMA, including POETYK PS0-1 and POETYK PSO-2. NMA, network meta-analysis; NRI, nonresponder imputation; PASI, Psoriasis Area and Severity Index; RCT, randomized controlled trial; SLR, systematic literature review. Figure 2. Network plots of trials included in the short- term (10–16 weeks; A), mid-term (24–28 weeks; B), and long-term (44–60 weeks; C) analyses v ETANERCEPT STUDY GROUP LIBERATE ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP FIXTURE M10-114 M10-315 OPT COMPARE STUDY reSURFACE 2 UNCOVER 2, 3 LIBERATE ESTEEM 1, 2 LIBERATE POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 2, 3 UNCOVER 1, 2, 3 ERASURE FEATURE FIXTURE JUNCTURE ALLURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMerge BE VIVID BE RADIANT BE READY BE VIVID ORION VOYAGE 1, 2 VOYAGE 1, 2 BE SURE IMMvent VOYAGE 1, 2 REVEAL CHAMPION EXPRESS EXPRESS II SPIRIT RESTORE 1 reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 1, 2 reSURFACE 2 ACCEPT UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE Reich, 2020 CHAMPION CHAMPION METOP ECLIPSE Blauvelt, 2021 IMMhance UltiMMa-1, -2 UltiMMa-1, -2 IXORA-5 ERASURE FEATURE FIXTURE JUNCTURE A. ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 UltiMMa-1, -2 UltiMMa-1, -2 POETYK 1 UNCOVER 3 AMAGINE 2, 3 AMAGINE 2, 3 IMMerge BE RADIANT VOYAGE 1 VOYAGE 1 VOYAGE 1 EXPRESS EXPRESS II FIXTURE FIXTUREFIXTURE METOP ECLIPSEIXORA-5 IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO LIBERATE CLEAR C. ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP ESTEEM 1, 2 POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 3 ERASURE FEATURE FIXTURE ERASURE FEATURE FIXTURE ALLURE ERASURE FEATURE FIXTURE AMAGINE 2, 3 BE VIVID AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMhance IMMerge BE RADIANT ORION VOYAGE 1, 2 VOYAGE 1, 2 VOYAGE 1, 2 BE SURE EXPRESS EXPRESS II reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 2 UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE METOP ECLIPSE IXORA-5 reSURFACE 1, 2 B. ETANERCEPT STUDY GROUP FIXTURE reSURFACE 2 ACT, acitretin; ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IXE, ixekizumab; MTX, methotrexate; PBO, placebo; RIS, risankizumab; Q2W, once every 2 weeks; SEC, secukinumab; TIL, tildrakizumab; UST, ustekinumab. • PASI 75 response rate with deucravacitinib at Week 16 (54.1%; credible interval [Crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [Crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [Crl, 74.0%, 83.5%] for infl iximab; Figure 3A) • PASI 75 response with deucravacitinib increased at Week 24 to 63.3% (Crl, 58.0%, 68.4%; Figure 3B) • At Week 52, the PASI 75 response rate for deucravacitinib (65.9%; Crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; Crl, 55.3%, 69.6%) and ustekinumab (68.0%; Crl, 64.6%, 71.5%; Figure 3C) • Newer IL-17 and IL-23 inhibitors showed the highest PASI 75 response rates of the included treatments, across all time points Figure 3. Short-term estimated PASI 75 response,a posterior median and 95% CrI. Weeks 10–16 (A), mid- term estimated PASI 75 response for Weeks 24–28 (B), and long-term estimated PASI 75 response for Weeks 44–60 (C) 56.7 IFX 5 mg/kg ADM 40 mg 62.8 48.4 APR 30 mg 45.0 MTX UST 90 mg 70.9 UST 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W BIM 320b mg TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 First-generation biologics Second-generation biologics A. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 PBO DEUC 6 mg ETC 50 mg BIW UST 45 or 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL–12/23 Anti–IL-17 Anti–IL-23 C. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg UST 45 or 90 mg UST 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti–TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 B. 74.675.074.271.0 72.3 72.2 73.4 First-generation biologics Second-generation biologics First-generation biologics Second-generation biologics aAdjusted for placebo response rates. bBIM is not approved for use in the United States. Note: posterior median value given for each therapy; error bars represent 95% CrI. ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; CrI, credible interval; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IL, interleukin; IXE, ixekizumab; MTX, methotrexate; NMA, network meta-analysis; PASI, Psoriasis Area and Severity Index; PBO, placebo; Q2W, once every 2 weeks; Q4W, once every 4 weeks; Q8W, once every 8 weeks; RIS, risankizumab; SEC, secukinumab; TIL, tildrakizumab; TNF, tumor necrosis factor; UST, ustekinumab. Conclusions • Among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • The PASI 75 response rates for deucravacitinib were within the range of those for first-generation biologics at Weeks 10–16 and 24–28 • At 1 year, the PASI 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • The psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies References 1. Guideline on Missing Data in Confirmatory Clinical Trials. European Medicines Agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. Guidance for Sponsors, Clinical Investigators, and IRBs. US Food and Drug Administration; 2008. http://www.fda.gov/downloads/ RegulatoryInformation/Guidances/ucm126489.pdf 3. Page MJ, et al. PLoS Med. 2021;18:e1003583. Acknowledgments • This study was sponsored by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Cheryl Jones of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AA: Grants and personal fees: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis; Personal fees: Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant; Grants: Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work • RBW: Research grants: AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB; Consulting fees: AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DiCE, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and UNION • YZ, JZ, RK, and CD: Employees of and may own stock options in Bristol Myers Squibb • AC, AK, DJ, and TW: Employed by Evidera, a company that provides consulting and other research services to Bristol Myers Squibb • MA: Advisory boards: AbbVie, Amgen, Boehringer Ingelheim, Janssen Biotech, and Leo Pharma; Consulting fees: AbbVie, Amgen, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Honoraria: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Investigator: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Leo Pharma, Merck, Novartis, Sun Pharma, and UCB; Research grants: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Janssen Biotech, Leo Pharma, Merck, and Sun Pharma; Speaker: AbbVie, Amgen, Janssen Biotech, Leo Pharma, Sun Pharma, and UCB Indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis April Armstrong,1 Richard B. Warren,2 Yichen Zhong,3 Joe Zhuo,3 Allie Cichewicz,4 Ananth Kadambi,4 Daniela R. Junqueira,4 Tracy Westley,4 Renata Kisa,3 Carolin Daamen,3 Matthias Augustin5 1University of Southern California, Los Angeles, CA; 2The University of Manchester, Manchester, UK; 3Bristol Myers Squibb, Princeton, NJ; 4Evidera, Bethesda, MD; 5University Medical Center, Hamburg, Germany Presented at the Fall Clinical Dermatology Conference; October 20–23, 2022; Las Vegas, NV This poster may not be reproduced without written permission from the authors.Email for April Armstrong, MD, MPH: AprilArmstrong@post.harvard.edu Scientifi c Content on Demand To request a copy of this poster: Scan QR code via a barcode reader application QR codes are valid for 30 days after congress presentation date Synopsis • Patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs) and is approved by the US Food and Drug Administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • This systematic literature review (SLR) and network meta-analysis (NMA) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the Psoriasis Area and Severity Index (PASI) at Weeks 10−16, 24−28, and 44−60 • PASI 75 (75% improvement in PASI) response rate with deucravacitinib was comparable to that of first-generation biologics at Week 16, and higher at Week 24; at Week 52, it was comparable to that of the most effective fi rst- generation biologics Objective • The objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis Methods • Electronic databases were searched through October 2021 for RCTs of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on PASI • Phase 3 trial data were included when: — Nonresponder imputation was applied1,2 — Studies were conducted in multiple or single countries with diverse ethnic representation • NMA was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate PASI responses over short-, mid-, and long-term follow-up periods (Weeks 10−16, 24−28, and 44−60, respectively) and reported following the PRISMA Reporting Guidelines for meta-analysis3 Results • The SLR identifi ed 47 phase 3 RCTs that applied nonresponder imputation and were included in the NMA (Figure 1 and Figure 2A); the mid-term analysis included 28 studies (Figure 2B); the long-term analysis included 21 studies (Figure 2C) Figure 1. PRISMA flow diagram Full-text articles excluded (n = 446) • Duplicates (n = 11) • Publication type not of interest (n = 17) • Study design not of interest (n = 25) • Population not of interest (n = 60) • Intervention/comparator not of interest (n = 105) • Outcomes not of interest (n = 189) • Relevant SLRs/NMAs published 2019-2020 (n = 39) Records excluded by title and abstract screening (n = 3632) Full-text articles assessed for eligibility (n = 818) 251 RCT publications and 132 pooleda analyses included in SLR Duplicates removed (n = 3037) RCTs included in global PASI NMA (n = 96 unique RCTs)b Records screened (n = 4450) RCTs included in phase 3 Global NRI PASI NMA (n = 47 unique RCTs)b Id e n ti fi ca ti o n Sc re e n in g E li gi b il it y In cl u d e d Records identified through database searching (n = 7487) Records identified through other sources (conference proceedings: n = 11) aPooled analyses of RCTs were not included in the SLR unless unique data were available that were not published elsewhere. bRCTs eligible for Global PASI NMA and phase 3 global NRI PASI NMA, including POETYK PS0-1 and POETYK PSO-2. NMA, network meta-analysis; NRI, nonresponder imputation; PASI, Psoriasis Area and Severity Index; RCT, randomized controlled trial; SLR, systematic literature review. Figure 2. Network plots of trials included in the short- term (10–16 weeks; A), mid-term (24–28 weeks; B), and long-term (44–60 weeks; C) analyses v ETANERCEPT STUDY GROUP LIBERATE ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP FIXTURE M10-114 M10-315 OPT COMPARE STUDY reSURFACE 2 UNCOVER 2, 3 LIBERATE ESTEEM 1, 2 LIBERATE POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 2, 3 UNCOVER 1, 2, 3 ERASURE FEATURE FIXTURE JUNCTURE ALLURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMerge BE VIVID BE RADIANT BE READY BE VIVID ORION VOYAGE 1, 2 VOYAGE 1, 2 BE SURE IMMvent VOYAGE 1, 2 REVEAL CHAMPION EXPRESS EXPRESS II SPIRIT RESTORE 1 reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 1, 2 reSURFACE 2 ACCEPT UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE Reich, 2020 CHAMPION CHAMPION METOP ECLIPSE Blauvelt, 2021 IMMhance UltiMMa-1, -2 UltiMMa-1, -2 IXORA-5 ERASURE FEATURE FIXTURE JUNCTURE A. ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 UltiMMa-1, -2 UltiMMa-1, -2 POETYK 1 UNCOVER 3 AMAGINE 2, 3 AMAGINE 2, 3 IMMerge BE RADIANT VOYAGE 1 VOYAGE 1 VOYAGE 1 EXPRESS EXPRESS II FIXTURE FIXTUREFIXTURE METOP ECLIPSEIXORA-5 IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO LIBERATE CLEAR C. ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP ESTEEM 1, 2 POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 3 ERASURE FEATURE FIXTURE ERASURE FEATURE FIXTURE ALLURE ERASURE FEATURE FIXTURE AMAGINE 2, 3 BE VIVID AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMhance IMMerge BE RADIANT ORION VOYAGE 1, 2 VOYAGE 1, 2 VOYAGE 1, 2 BE SURE EXPRESS EXPRESS II reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 2 UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE METOP ECLIPSE IXORA-5 reSURFACE 1, 2 B. ETANERCEPT STUDY GROUP FIXTURE reSURFACE 2 ACT, acitretin; ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IXE, ixekizumab; MTX, methotrexate; PBO, placebo; RIS, risankizumab; Q2W, once every 2 weeks; SEC, secukinumab; TIL, tildrakizumab; UST, ustekinumab. • PASI 75 response rate with deucravacitinib at Week 16 (54.1%; credible interval [Crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [Crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [Crl, 74.0%, 83.5%] for infl iximab; Figure 3A) • PASI 75 response with deucravacitinib increased at Week 24 to 63.3% (Crl, 58.0%, 68.4%; Figure 3B) • At Week 52, the PASI 75 response rate for deucravacitinib (65.9%; Crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; Crl, 55.3%, 69.6%) and ustekinumab (68.0%; Crl, 64.6%, 71.5%; Figure 3C) • Newer IL-17 and IL-23 inhibitors showed the highest PASI 75 response rates of the included treatments, across all time points Figure 3. Short-term estimated PASI 75 response,a posterior median and 95% CrI. Weeks 10–16 (A), mid- term estimated PASI 75 response for Weeks 24–28 (B), and long-term estimated PASI 75 response for Weeks 44–60 (C) 56.7 IFX 5 mg/kg ADM 40 mg 62.8 48.4 APR 30 mg 45.0 MTX UST 90 mg 70.9 UST 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W BIM 320b mg TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 First-generation biologics Second-generation biologics A. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 PBO DEUC 6 mg ETC 50 mg BIW UST 45 or 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL–12/23 Anti–IL-17 Anti–IL-23 C. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg UST 45 or 90 mg UST 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti–TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 B. 74.675.074.271.0 72.3 72.2 73.4 First-generation biologics Second-generation biologics First-generation biologics Second-generation biologics aAdjusted for placebo response rates. bBIM is not approved for use in the United States. Note: posterior median value given for each therapy; error bars represent 95% CrI. ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; CrI, credible interval; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IL, interleukin; IXE, ixekizumab; MTX, methotrexate; NMA, network meta-analysis; PASI, Psoriasis Area and Severity Index; PBO, placebo; Q2W, once every 2 weeks; Q4W, once every 4 weeks; Q8W, once every 8 weeks; RIS, risankizumab; SEC, secukinumab; TIL, tildrakizumab; TNF, tumor necrosis factor; UST, ustekinumab. Conclusions • Among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • The PASI 75 response rates for deucravacitinib were within the range of those for first-generation biologics at Weeks 10–16 and 24–28 • At 1 year, the PASI 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • The psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies References 1. Guideline on Missing Data in Confirmatory Clinical Trials. European Medicines Agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. Guidance for Sponsors, Clinical Investigators, and IRBs. US Food and Drug Administration; 2008. http://www.fda.gov/downloads/ RegulatoryInformation/Guidances/ucm126489.pdf 3. Page MJ, et al. PLoS Med. 2021;18:e1003583. Acknowledgments • This study was sponsored by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Cheryl Jones of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AA: Grants and personal fees: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis; Personal fees: Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant; Grants: Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work • RBW: Research grants: AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB; Consulting fees: AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DiCE, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and UNION • YZ, JZ, RK, and CD: Employees of and may own stock options in Bristol Myers Squibb • AC, AK, DJ, and TW: Employed by Evidera, a company that provides consulting and other research services to Bristol Myers Squibb • MA: Advisory boards: AbbVie, Amgen, Boehringer Ingelheim, Janssen Biotech, and Leo Pharma; Consulting fees: AbbVie, Amgen, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Honoraria: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Investigator: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Leo Pharma, Merck, Novartis, Sun Pharma, and UCB; Research grants: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Janssen Biotech, Leo Pharma, Merck, and Sun Pharma; Speaker: AbbVie, Amgen, Janssen Biotech, Leo Pharma, Sun Pharma, and UCB Indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis April Armstrong,1 Richard B. Warren,2 Yichen Zhong,3 Joe Zhuo,3 Allie Cichewicz,4 Ananth Kadambi,4 Daniela R. Junqueira,4 Tracy Westley,4 Renata Kisa,3 Carolin Daamen,3 Matthias Augustin5 1University of Southern California, Los Angeles, CA; 2The University of Manchester, Manchester, UK; 3Bristol Myers Squibb, Princeton, NJ; 4Evidera, Bethesda, MD; 5University Medical Center, Hamburg, Germany Presented at the Fall Clinical Dermatology Conference; October 20–23, 2022; Las Vegas, NV This poster may not be reproduced without written permission from the authors.Email for April Armstrong, MD, MPH: AprilArmstrong@post.harvard.edu Scientifi c Content on Demand To request a copy of this poster: Scan QR code via a barcode reader application QR codes are valid for 30 days after congress presentation date Synopsis • Patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs) and is approved by the US Food and Drug Administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • This systematic literature review (SLR) and network meta-analysis (NMA) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the Psoriasis Area and Severity Index (PASI) at Weeks 10−16, 24−28, and 44−60 • PASI 75 (75% improvement in PASI) response rate with deucravacitinib was comparable to that of first-generation biologics at Week 16, and higher at Week 24; at Week 52, it was comparable to that of the most effective fi rst- generation biologics Objective • The objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis Methods • Electronic databases were searched through October 2021 for RCTs of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on PASI • Phase 3 trial data were included when: — Nonresponder imputation was applied1,2 — Studies were conducted in multiple or single countries with diverse ethnic representation • NMA was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate PASI responses over short-, mid-, and long-term follow-up periods (Weeks 10−16, 24−28, and 44−60, respectively) and reported following the PRISMA Reporting Guidelines for meta-analysis3 Results • The SLR identifi ed 47 phase 3 RCTs that applied nonresponder imputation and were included in the NMA (Figure 1 and Figure 2A); the mid-term analysis included 28 studies (Figure 2B); the long-term analysis included 21 studies (Figure 2C) Figure 1. PRISMA flow diagram Full-text articles excluded (n = 446) • Duplicates (n = 11) • Publication type not of interest (n = 17) • Study design not of interest (n = 25) • Population not of interest (n = 60) • Intervention/comparator not of interest (n = 105) • Outcomes not of interest (n = 189) • Relevant SLRs/NMAs published 2019-2020 (n = 39) Records excluded by title and abstract screening (n = 3632) Full-text articles assessed for eligibility (n = 818) 251 RCT publications and 132 pooleda analyses included in SLR Duplicates removed (n = 3037) RCTs included in global PASI NMA (n = 96 unique RCTs)b Records screened (n = 4450) RCTs included in phase 3 Global NRI PASI NMA (n = 47 unique RCTs)b Id e n ti fi ca ti o n Sc re e n in g E li gi b il it y In cl u d e d Records identified through database searching (n = 7487) Records identified through other sources (conference proceedings: n = 11) aPooled analyses of RCTs were not included in the SLR unless unique data were available that were not published elsewhere. bRCTs eligible for Global PASI NMA and phase 3 global NRI PASI NMA, including POETYK PS0-1 and POETYK PSO-2. NMA, network meta-analysis; NRI, nonresponder imputation; PASI, Psoriasis Area and Severity Index; RCT, randomized controlled trial; SLR, systematic literature review. Figure 2. Network plots of trials included in the short- term (10–16 weeks; A), mid-term (24–28 weeks; B), and long-term (44–60 weeks; C) analyses v ETANERCEPT STUDY GROUP LIBERATE ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP FIXTURE M10-114 M10-315 OPT COMPARE STUDY reSURFACE 2 UNCOVER 2, 3 LIBERATE ESTEEM 1, 2 LIBERATE POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 2, 3 UNCOVER 1, 2, 3 ERASURE FEATURE FIXTURE JUNCTURE ALLURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMerge BE VIVID BE RADIANT BE READY BE VIVID ORION VOYAGE 1, 2 VOYAGE 1, 2 BE SURE IMMvent VOYAGE 1, 2 REVEAL CHAMPION EXPRESS EXPRESS II SPIRIT RESTORE 1 reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 1, 2 reSURFACE 2 ACCEPT UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE Reich, 2020 CHAMPION CHAMPION METOP ECLIPSE Blauvelt, 2021 IMMhance UltiMMa-1, -2 UltiMMa-1, -2 IXORA-5 ERASURE FEATURE FIXTURE JUNCTURE A. ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE ERASURE FEATURE FIXTURE JUNCTURE AMAGINE 2, 3 BE VIVID UltiMMA-1, -2 UltiMMa-1, -2 UltiMMa-1, -2 POETYK 1 UNCOVER 3 AMAGINE 2, 3 AMAGINE 2, 3 IMMerge BE RADIANT VOYAGE 1 VOYAGE 1 VOYAGE 1 EXPRESS EXPRESS II FIXTURE FIXTUREFIXTURE METOP ECLIPSEIXORA-5 IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO LIBERATE CLEAR C. ETANERCEPT STUDY GROUP ETANERCEPT STUDY GROUP ESTEEM 1, 2 POETYK 1, 2POETYK 1, 2 FIXTURE POETYK 1, 2 UNCOVER 3 ERASURE FEATURE FIXTURE ERASURE FEATURE FIXTURE ALLURE ERASURE FEATURE FIXTURE AMAGINE 2, 3 BE VIVID AMAGINE 1, 2, 3 AMAGINE 2, 3 CLEAR IMMhance IMMerge BE RADIANT ORION VOYAGE 1, 2 VOYAGE 1, 2 VOYAGE 1, 2 BE SURE EXPRESS EXPRESS II reSURFACE 1, 2 reSURFACE 1, 2 PHOENIX 1, 2 reSURFACE 2 UST 90 mg TIL 200 mg TIL 100 mg IFX 5 mg/kg MTX 7.5 to 25 mg ADM 40 mgGUS 100 mg BIM 320 mg UST 45 or 90 mg SEC 300 mg SEC 150 mg APR 30 mg ETC 25 mg BIW ETC 50 mg BIW DEUC 6 mg IXE 80 mg Q2W BRO 210 mg RIS 150 mg PBO reSURFACE 2 FIXTURE METOP ECLIPSE IXORA-5 reSURFACE 1, 2 B. ETANERCEPT STUDY GROUP FIXTURE reSURFACE 2 ACT, acitretin; ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IXE, ixekizumab; MTX, methotrexate; PBO, placebo; RIS, risankizumab; Q2W, once every 2 weeks; SEC, secukinumab; TIL, tildrakizumab; UST, ustekinumab. • PASI 75 response rate with deucravacitinib at Week 16 (54.1%; credible interval [Crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [Crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [Crl, 74.0%, 83.5%] for infl iximab; Figure 3A) • PASI 75 response with deucravacitinib increased at Week 24 to 63.3% (Crl, 58.0%, 68.4%; Figure 3B) • At Week 52, the PASI 75 response rate for deucravacitinib (65.9%; Crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; Crl, 55.3%, 69.6%) and ustekinumab (68.0%; Crl, 64.6%, 71.5%; Figure 3C) • Newer IL-17 and IL-23 inhibitors showed the highest PASI 75 response rates of the included treatments, across all time points Figure 3. Short-term estimated PASI 75 response,a posterior median and 95% CrI. Weeks 10–16 (A), mid- term estimated PASI 75 response for Weeks 24–28 (B), and long-term estimated PASI 75 response for Weeks 44–60 (C) 56.7 IFX 5 mg/kg ADM 40 mg 62.8 48.4 APR 30 mg 45.0 MTX UST 90 mg 70.9 UST 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W BIM 320b mg TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 First-generation biologics Second-generation biologics A. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 PBO DEUC 6 mg ETC 50 mg BIW UST 45 or 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti-TNF Anti–IL–12/23 Anti–IL-17 Anti–IL-23 C. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 PBO APR 30 mg MTX DEUC 6 mg ETC 25 mg BIW/50 mg QW ETC 50 mg BIW ADM 40 mg IFX 5 mg/kg UST 45 or 90 mg UST 90 mg SEC 150 mg SEC 300 mg BRO 210 mg IXE 80 mg Q2W>Q4W BIM 320b mg Q4W>Q8W TIL 100 mg TIL 200 mg GUS 100 mg RIS 150 mg N M A e st im at e d P A SI 7 5 re sp on se r at e , % Nonbiologic oral Anti–TNF Anti–IL-12/23 Anti–IL-17 Anti–IL-23 B. 74.675.074.271.0 72.3 72.2 73.4 First-generation biologics Second-generation biologics First-generation biologics Second-generation biologics aAdjusted for placebo response rates. bBIM is not approved for use in the United States. Note: posterior median value given for each therapy; error bars represent 95% CrI. ADM, adalimumab; APR, apremilast; BIM, bimekizumab; BIW, twice weekly; BRO, brodalumab; CrI, credible interval; DEUC, deucravacitinib; ETC, etanercept; GUS, guselkumab; IFX, infl iximab; IL, interleukin; IXE, ixekizumab; MTX, methotrexate; NMA, network meta-analysis; PASI, Psoriasis Area and Severity Index; PBO, placebo; Q2W, once every 2 weeks; Q4W, once every 4 weeks; Q8W, once every 8 weeks; RIS, risankizumab; SEC, secukinumab; TIL, tildrakizumab; TNF, tumor necrosis factor; UST, ustekinumab. Conclusions • Among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • The PASI 75 response rates for deucravacitinib were within the range of those for first-generation biologics at Weeks 10–16 and 24–28 • At 1 year, the PASI 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • The psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies References 1. Guideline on Missing Data in Confirmatory Clinical Trials. European Medicines Agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. Guidance for Sponsors, Clinical Investigators, and IRBs. US Food and Drug Administration; 2008. http://www.fda.gov/downloads/ RegulatoryInformation/Guidances/ucm126489.pdf 3. Page MJ, et al. PLoS Med. 2021;18:e1003583. Acknowledgments • This study was sponsored by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Cheryl Jones of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AA: Grants and personal fees: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis; Personal fees: Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant; Grants: Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work • RBW: Research grants: AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB; Consulting fees: AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DiCE, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and UNION • YZ, JZ, RK, and CD: Employees of and may own stock options in Bristol Myers Squibb • AC, AK, DJ, and TW: Employed by Evidera, a company that provides consulting and other research services to Bristol Myers Squibb • MA: Advisory boards: AbbVie, Amgen, Boehringer Ingelheim, Janssen Biotech, and Leo Pharma; Consulting fees: AbbVie, Amgen, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Honoraria: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Investigator: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Leo Pharma, Merck, Novartis, Sun Pharma, and UCB; Research grants: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Janssen Biotech, Leo Pharma, Merck, and Sun Pharma; Speaker: AbbVie, Amgen, Janssen Biotech, Leo Pharma, Sun Pharma, and UCB