Optimizing the treatment sequence: the cumulative clinical benefi t of treatment initiation with deucravacitinib versus apremilast over 52 weeks in patients with moderate to severe plaque psoriasis from the POETYK PSO-1 trial April W. Armstrong,1 Sang Hee Park,2 Viktor Chirikov,3 Pierre Nicolas,2,4 Wei-Jhih Wang,3 Matthew J. Colombo,2 Vardhaman Patel2 1Keck School of Medicine, University of Southern California, Los Angeles, CA; 2Bristol Myers Squibb, Princeton, NJ; 3OPEN Health, Bethesda, MD; 4Bristol Myers Squibb, Boudry, Switzerland 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 • Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor 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 • In the recent phase 3 clinical trial POETYK PSO-1, patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib, placebo, or apremilast1 — Patients receiving apremilast who did not achieve at least 50% improvement from baseline in Psoriasis Area and Severity Index score (PASI 50) at Week 24 crossed over to deucravacitinib1 • At Week 52, 46.3% of these patients achieved at least 75% improvement from baseline in PASI score (PASI 75), and 42.6% achieved a static Physician Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1)2 — Patients receiving apremilast who achieved PASI 50 at Week 24 continued with apremilast — Patients who received placebo are not represented in this analysis • This study evaluated the cumulative clinical benefit of initiating with deucravacitinib vs apremilast to determine the treatment pathway that provides greater benefit to the patient — The cumulative clinical benefit refl ects the total time patients spend in a state of therapeutic response3 • The results of this study indicate that initiating deucravacitinib as a first-line treatment offers greater benefits over time compared with initiating with apremilast Objective • To evaluate the cumulative clinical benefit of initiating with deucravacitinib vs apremilast from baseline to Week 52 based on data from POETYK PSO-1 Methods • POETYK PSO-1 was a multicenter, randomized, double-blind, placebo- and active comparator–controlled study1 — Patients were aged ≥18 years and had moderate to severe plaque psoriasis (PASI score ≥12, sPGA score ≥3, and body surface area involvement ≥10%) — Coprimary effi cacy endpoints were PASI 75 and sPGA 0/1 — Nonresponder imputation was used for missing data • This post hoc analysis compared data from 2 arms in the POETYK PSO-1 trial (Figure 1) — Deucravacitinib arm: patients initiated with and continued on deucravacitinib, regardless of response status — Apremilast initiators arm: patients initiated with apremilast; at Week 24, PASI 50 responders continued with apremilast while PASI 50 nonresponders crossed over to deucravacitinib • Cumulative clinical benefit from randomization to Week 52 was determined by the total area under the curve of clinical response over 52 weeks (AUC 0–52wk ) in each arm — AUC analysis has been employed to evaluate outcomes over time in clinical trials, as the AUC refl ects the rapidity and durability, as well as the magnitude, of response3-6 • While assessments at discrete time points identify static responses, the AUC approach captures cumulative treatment effects over time — This study determined the AUC using data at a patient level (responder status at each time point over 52 weeks) • Total AUC 0–52wk was calculated separately for each efficacy endpoint, using the trapezoidal rule — Total AUC 0–52wk = 15i=0∑ (Pi+Pi+1)(Ti+1−Ti), where Ti (i = 0, 1, 2, 3, …, 15) denotes the time points of Weeks 0, 1, 2, 4, 8, 12, and 16, then every 4 weeks thereafter through Week 52, and P i denotes the response (yes = 1; no = 0) at each time point, T i • The result was standardized as a percentage of maximum possible AUC 0–52wk (0–5200 [% × weeks]) and aggregated to the population level • Adjusted AUC comparisons between the 2 treatment arms were based on an analysis of covariance (ANCOVA) model, with the following stratification parameters: — Prior use of a biologic treatment (yes/no) — Region (United States, China, Japan, rest of the world [ROW]) — Body weight (<90 kg, ≥90 kg), in the United States and ROW only • Ratios of AUC 0–52wk were calculated, representing the relative cumulative clinical benefit of the 2 treatment pathways for achieving PASI 75 or sPGA 0/1 over the 52-week period Figure 1. Study design comparing data from 2 arms of POETYK PSO-1 Week 0 Week 24 Week 52 Apremilast initiators arm (n = 168) Deucravacitinib arm (n = 332) Initiation of deucravacitinib Continuation of deucravacitinib Initiation of apremilast ≥PASI 50: continuation of apremilast <PASI 50: initiation of deucravacitinib PASI 50, 50% improvement from baseline in Psoriasis Area and Severity Index score. Results PASI 75 • Standardized average cumulative PASI 75 response over 52 weeks among patients initiating with deucravacitinib was 57.3% compared with 38.2% in patients initiating with apremilast (including 87 patients who continued apremilast after Week 24 and 54 patients who switched to deucravacitinib) (Table 1) — Adjusted AUC 0–52wk [% × weeks] was 2978.72 in the deucravacitinib arm and 1988.06 in the apremilast initiatiors arm — The adjusted difference in AUC 0–52wk was 990.66 (95% CI, 683.37–1297.95); P < 0.001 — The benefit ratio of initiating with deucravacitinib vs apremilast was 1.50 • Figure 2 displays the standardized adjusted cumulative AUC for PASI 75 over 52 weeks sPGA 0/1 • Standardized average cumulative sPGA 0/1 response over 52 weeks among patients initiating with deucravacitinib was 50.2% compared with 31.9% in patients initiating with apremilast (Table 2) — Adjusted AUC 0–52wk [% × weeks] was 2612.82 in the deucravacitinib arm and 1657.13 in the apremilast initiators arm — The adjusted difference in AUC 0–52wk was 955.69 (95% CI, 642.22–1269.16); P < 0.001 — The benefit ratio of initiating with deucravacitinib vs apremilast was 1.58 • Figure 3 displays the standardized adjusted cumulative AUC for sPGA 0/1 over 52 weeks Table 1. Cumulative clinical benefit measured by PASI 75 response over 52 weeks Outcomes Deucravacitinib, n = 332 Apremilast initiators,a n = 168 Difference in estimate (95% CI) P value Benefit ratio Adjusted AUC 0–52wk , % × weeks 2978.72 1988.06 990.66 (683.37–1297.95) < 0.001 1.50 Standardized average cumulative responseb 57.3% 38.2% — — aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. bAUC 0–52wk /maximum AUC 0–52wk . AUC 0–52wk , area under the curve over 52 weeks; CI, confidence interval; PASI 75, 75% improvement from baseline in Psoriasis Area and Severity Index score. Figure 2. Standardized adjusted AUC 0–52wk : PASI 75 0 10 20 30 40 50 60 St an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Deucravacitinib (n = 332) Apremilast initiators (n = 168)a aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. AUC 0–52wk , area under the curve over 52 weeks; PASI 50/75, ≥50%/≥75% improvement from baseline in Psoriasis Area and Severity Index score. Table 2. Cumulative clinical benefit measured by sPGA 0/1 response over 52 weeks Outcomes Deucravacitinib, n = 332 Apremilast initiators,a n = 168 Difference in estimate (95% CI) P value Benefit ratio Adjusted AUC 0–52wk , % × weeks 2612.82 1657.13 955.69 (642.22–1269.16) < 0.001 1.58 Standardized average cumulative responseb 50.2% 31.9% — — aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. bAUC 0–52wk /maximum AUC 0–52wk . AUC 0–52wk , area under the curve over 52 weeks; CI, confidence interval; sPGA 0/1, static Physician Global Assessment score of 0 or 1. Figure 3. Standardized adjusted AUC 0–52wk : sPGA 0/1 Deucravacitinib (n = 332) Apremilast initiators (n = 168)a 0 10 20 30 40 50 60 St an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. AUC 0–52wk , area under the curve over 52 weeks; PASI 50, ≥50% improvement from baseline in Psoriasis Area and Severity Index score; sPGA, static Physician Global Assessment score of 0 or 1. Conclusions • Initiating with deucravacitinib resulted in greater cumulative benefits over 52 weeks than initiating with apremilast — Deucravacitinib initiators spend ≈150% more time in therapeutic response over 1 year compared with apremilast initiators • Initiating with deucravacitinib as the first line rather than switching to deucravacitinib as the second line after failure to respond with apremilast may optimize the clinical benefit that patients receive References 1. Armstrong AW, et al. J Am Acad Dermatol. 2022;S0190-9622 [online ahead of print]. 2. Armstrong AW, et al. [poster] Presented at the American Academy of Dermatology Annual Meeting, March 25–29, 2022, Boston, MA. 3. Armstrong AW, et al. J Dermatolog Treat. 2017;28:200-205. 4. Bushmakin AG, et al. Qual Life Res. 2011;20:491-498. 5. Warren RB, et al. J Eur Acad Dermatol Venereol. 2021;35:450-457. 6. Blauvelt A, et al. J Manag Care Spec Pharm. 2021;27:84-94. Acknowledgments • This study was supported by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Eleanor Bush, MA, of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AWA: 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 • SHP, VP, PN, MJC: Employees of and may own stock options in Bristol Myers Squibb • W-JW, VC: Employees of OPEN Health, which has received consulting fees from Bristol Myers Squibb 1 2 Optimizing the treatment sequence: the cumulative clinical benefi t of treatment initiation with deucravacitinib versus apremilast over 52 weeks in patients with moderate to severe plaque psoriasis from the POETYK PSO-1 trial April W. Armstrong,1 Sang Hee Park,2 Viktor Chirikov,3 Pierre Nicolas,2,4 Wei-Jhih Wang,3 Matthew J. Colombo,2 Vardhaman Patel2 1Keck School of Medicine, University of Southern California, Los Angeles, CA; 2Bristol Myers Squibb, Princeton, NJ; 3OPEN Health, Bethesda, MD; 4Bristol Myers Squibb, Boudry, Switzerland 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 • Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor 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 • In the recent phase 3 clinical trial POETYK PSO-1, patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib, placebo, or apremilast1 — Patients receiving apremilast who did not achieve at least 50% improvement from baseline in Psoriasis Area and Severity Index score (PASI 50) at Week 24 crossed over to deucravacitinib1 • At Week 52, 46.3% of these patients achieved at least 75% improvement from baseline in PASI score (PASI 75), and 42.6% achieved a static Physician Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1)2 — Patients receiving apremilast who achieved PASI 50 at Week 24 continued with apremilast — Patients who received placebo are not represented in this analysis • This study evaluated the cumulative clinical benefit of initiating with deucravacitinib vs apremilast to determine the treatment pathway that provides greater benefit to the patient — The cumulative clinical benefit refl ects the total time patients spend in a state of therapeutic response3 • The results of this study indicate that initiating deucravacitinib as a first-line treatment offers greater benefits over time compared with initiating with apremilast Objective • To evaluate the cumulative clinical benefit of initiating with deucravacitinib vs apremilast from baseline to Week 52 based on data from POETYK PSO-1 Methods • POETYK PSO-1 was a multicenter, randomized, double-blind, placebo- and active comparator–controlled study1 — Patients were aged ≥18 years and had moderate to severe plaque psoriasis (PASI score ≥12, sPGA score ≥3, and body surface area involvement ≥10%) — Coprimary effi cacy endpoints were PASI 75 and sPGA 0/1 — Nonresponder imputation was used for missing data • This post hoc analysis compared data from 2 arms in the POETYK PSO-1 trial (Figure 1) — Deucravacitinib arm: patients initiated with and continued on deucravacitinib, regardless of response status — Apremilast initiators arm: patients initiated with apremilast; at Week 24, PASI 50 responders continued with apremilast while PASI 50 nonresponders crossed over to deucravacitinib • Cumulative clinical benefit from randomization to Week 52 was determined by the total area under the curve of clinical response over 52 weeks (AUC 0–52wk ) in each arm — AUC analysis has been employed to evaluate outcomes over time in clinical trials, as the AUC refl ects the rapidity and durability, as well as the magnitude, of response3-6 • While assessments at discrete time points identify static responses, the AUC approach captures cumulative treatment effects over time — This study determined the AUC using data at a patient level (responder status at each time point over 52 weeks) • Total AUC 0–52wk was calculated separately for each efficacy endpoint, using the trapezoidal rule — Total AUC 0–52wk = 15i=0∑ (Pi+Pi+1)(Ti+1−Ti), where Ti (i = 0, 1, 2, 3, …, 15) denotes the time points of Weeks 0, 1, 2, 4, 8, 12, and 16, then every 4 weeks thereafter through Week 52, and P i denotes the response (yes = 1; no = 0) at each time point, T i • The result was standardized as a percentage of maximum possible AUC 0–52wk (0–5200 [% × weeks]) and aggregated to the population level • Adjusted AUC comparisons between the 2 treatment arms were based on an analysis of covariance (ANCOVA) model, with the following stratification parameters: — Prior use of a biologic treatment (yes/no) — Region (United States, China, Japan, rest of the world [ROW]) — Body weight (<90 kg, ≥90 kg), in the United States and ROW only • Ratios of AUC 0–52wk were calculated, representing the relative cumulative clinical benefit of the 2 treatment pathways for achieving PASI 75 or sPGA 0/1 over the 52-week period Figure 1. Study design comparing data from 2 arms of POETYK PSO-1 Week 0 Week 24 Week 52 Apremilast initiators arm (n = 168) Deucravacitinib arm (n = 332) Initiation of deucravacitinib Continuation of deucravacitinib Initiation of apremilast ≥PASI 50: continuation of apremilast <PASI 50: initiation of deucravacitinib PASI 50, 50% improvement from baseline in Psoriasis Area and Severity Index score. Results PASI 75 • Standardized average cumulative PASI 75 response over 52 weeks among patients initiating with deucravacitinib was 57.3% compared with 38.2% in patients initiating with apremilast (including 87 patients who continued apremilast after Week 24 and 54 patients who switched to deucravacitinib) (Table 1) — Adjusted AUC 0–52wk [% × weeks] was 2978.72 in the deucravacitinib arm and 1988.06 in the apremilast initiatiors arm — The adjusted difference in AUC 0–52wk was 990.66 (95% CI, 683.37–1297.95); P < 0.001 — The benefit ratio of initiating with deucravacitinib vs apremilast was 1.50 • Figure 2 displays the standardized adjusted cumulative AUC for PASI 75 over 52 weeks sPGA 0/1 • Standardized average cumulative sPGA 0/1 response over 52 weeks among patients initiating with deucravacitinib was 50.2% compared with 31.9% in patients initiating with apremilast (Table 2) — Adjusted AUC 0–52wk [% × weeks] was 2612.82 in the deucravacitinib arm and 1657.13 in the apremilast initiators arm — The adjusted difference in AUC 0–52wk was 955.69 (95% CI, 642.22–1269.16); P < 0.001 — The benefit ratio of initiating with deucravacitinib vs apremilast was 1.58 • Figure 3 displays the standardized adjusted cumulative AUC for sPGA 0/1 over 52 weeks Table 1. Cumulative clinical benefit measured by PASI 75 response over 52 weeks Outcomes Deucravacitinib, n = 332 Apremilast initiators,a n = 168 Difference in estimate (95% CI) P value Benefit ratio Adjusted AUC 0–52wk , % × weeks 2978.72 1988.06 990.66 (683.37–1297.95) < 0.001 1.50 Standardized average cumulative responseb 57.3% 38.2% — — aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. bAUC 0–52wk /maximum AUC 0–52wk . AUC 0–52wk , area under the curve over 52 weeks; CI, confidence interval; PASI 75, 75% improvement from baseline in Psoriasis Area and Severity Index score. Figure 2. Standardized adjusted AUC 0–52wk : PASI 75 0 10 20 30 40 50 60 St an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Deucravacitinib (n = 332) Apremilast initiators (n = 168)a aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. AUC 0–52wk , area under the curve over 52 weeks; PASI 50/75, ≥50%/≥75% improvement from baseline in Psoriasis Area and Severity Index score. Table 2. Cumulative clinical benefit measured by sPGA 0/1 response over 52 weeks Outcomes Deucravacitinib, n = 332 Apremilast initiators,a n = 168 Difference in estimate (95% CI) P value Benefit ratio Adjusted AUC 0–52wk , % × weeks 2612.82 1657.13 955.69 (642.22–1269.16) < 0.001 1.58 Standardized average cumulative responseb 50.2% 31.9% — — aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. bAUC 0–52wk /maximum AUC 0–52wk . AUC 0–52wk , area under the curve over 52 weeks; CI, confidence interval; sPGA 0/1, static Physician Global Assessment score of 0 or 1. Figure 3. Standardized adjusted AUC 0–52wk : sPGA 0/1 Deucravacitinib (n = 332) Apremilast initiators (n = 168)a 0 10 20 30 40 50 60 St an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. AUC 0–52wk , area under the curve over 52 weeks; PASI 50, ≥50% improvement from baseline in Psoriasis Area and Severity Index score; sPGA, static Physician Global Assessment score of 0 or 1. Conclusions • Initiating with deucravacitinib resulted in greater cumulative benefits over 52 weeks than initiating with apremilast — Deucravacitinib initiators spend ≈150% more time in therapeutic response over 1 year compared with apremilast initiators • Initiating with deucravacitinib as the first line rather than switching to deucravacitinib as the second line after failure to respond with apremilast may optimize the clinical benefit that patients receive References 1. Armstrong AW, et al. J Am Acad Dermatol. 2022;S0190-9622 [online ahead of print]. 2. Armstrong AW, et al. [poster] Presented at the American Academy of Dermatology Annual Meeting, March 25–29, 2022, Boston, MA. 3. Armstrong AW, et al. J Dermatolog Treat. 2017;28:200-205. 4. Bushmakin AG, et al. Qual Life Res. 2011;20:491-498. 5. Warren RB, et al. J Eur Acad Dermatol Venereol. 2021;35:450-457. 6. Blauvelt A, et al. J Manag Care Spec Pharm. 2021;27:84-94. Acknowledgments • This study was supported by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Eleanor Bush, MA, of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AWA: 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 • SHP, VP, PN, MJC: Employees of and may own stock options in Bristol Myers Squibb • W-JW, VC: Employees of OPEN Health, which has received consulting fees from Bristol Myers Squibb 1 2 Optimizing the treatment sequence: the cumulative clinical benefi t of treatment initiation with deucravacitinib versus apremilast over 52 weeks in patients with moderate to severe plaque psoriasis from the POETYK PSO-1 trial April W. Armstrong,1 Sang Hee Park,2 Viktor Chirikov,3 Pierre Nicolas,2,4 Wei-Jhih Wang,3 Matthew J. Colombo,2 Vardhaman Patel2 1Keck School of Medicine, University of Southern California, Los Angeles, CA; 2Bristol Myers Squibb, Princeton, NJ; 3OPEN Health, Bethesda, MD; 4Bristol Myers Squibb, Boudry, Switzerland 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 • Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor 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 • In the recent phase 3 clinical trial POETYK PSO-1, patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib, placebo, or apremilast1 — Patients receiving apremilast who did not achieve at least 50% improvement from baseline in Psoriasis Area and Severity Index score (PASI 50) at Week 24 crossed over to deucravacitinib1 • At Week 52, 46.3% of these patients achieved at least 75% improvement from baseline in PASI score (PASI 75), and 42.6% achieved a static Physician Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1)2 — Patients receiving apremilast who achieved PASI 50 at Week 24 continued with apremilast — Patients who received placebo are not represented in this analysis • This study evaluated the cumulative clinical benefit of initiating with deucravacitinib vs apremilast to determine the treatment pathway that provides greater benefit to the patient — The cumulative clinical benefit refl ects the total time patients spend in a state of therapeutic response3 • The results of this study indicate that initiating deucravacitinib as a first-line treatment offers greater benefits over time compared with initiating with apremilast Objective • To evaluate the cumulative clinical benefit of initiating with deucravacitinib vs apremilast from baseline to Week 52 based on data from POETYK PSO-1 Methods • POETYK PSO-1 was a multicenter, randomized, double-blind, placebo- and active comparator–controlled study1 — Patients were aged ≥18 years and had moderate to severe plaque psoriasis (PASI score ≥12, sPGA score ≥3, and body surface area involvement ≥10%) — Coprimary effi cacy endpoints were PASI 75 and sPGA 0/1 — Nonresponder imputation was used for missing data • This post hoc analysis compared data from 2 arms in the POETYK PSO-1 trial (Figure 1) — Deucravacitinib arm: patients initiated with and continued on deucravacitinib, regardless of response status — Apremilast initiators arm: patients initiated with apremilast; at Week 24, PASI 50 responders continued with apremilast while PASI 50 nonresponders crossed over to deucravacitinib • Cumulative clinical benefit from randomization to Week 52 was determined by the total area under the curve of clinical response over 52 weeks (AUC 0–52wk ) in each arm — AUC analysis has been employed to evaluate outcomes over time in clinical trials, as the AUC refl ects the rapidity and durability, as well as the magnitude, of response3-6 • While assessments at discrete time points identify static responses, the AUC approach captures cumulative treatment effects over time — This study determined the AUC using data at a patient level (responder status at each time point over 52 weeks) • Total AUC 0–52wk was calculated separately for each efficacy endpoint, using the trapezoidal rule — Total AUC 0–52wk = 15i=0∑ (Pi+Pi+1)(Ti+1−Ti), where Ti (i = 0, 1, 2, 3, …, 15) denotes the time points of Weeks 0, 1, 2, 4, 8, 12, and 16, then every 4 weeks thereafter through Week 52, and P i denotes the response (yes = 1; no = 0) at each time point, T i • The result was standardized as a percentage of maximum possible AUC 0–52wk (0–5200 [% × weeks]) and aggregated to the population level • Adjusted AUC comparisons between the 2 treatment arms were based on an analysis of covariance (ANCOVA) model, with the following stratification parameters: — Prior use of a biologic treatment (yes/no) — Region (United States, China, Japan, rest of the world [ROW]) — Body weight (<90 kg, ≥90 kg), in the United States and ROW only • Ratios of AUC 0–52wk were calculated, representing the relative cumulative clinical benefit of the 2 treatment pathways for achieving PASI 75 or sPGA 0/1 over the 52-week period Figure 1. Study design comparing data from 2 arms of POETYK PSO-1 Week 0 Week 24 Week 52 Apremilast initiators arm (n = 168) Deucravacitinib arm (n = 332) Initiation of deucravacitinib Continuation of deucravacitinib Initiation of apremilast ≥PASI 50: continuation of apremilast <PASI 50: initiation of deucravacitinib PASI 50, 50% improvement from baseline in Psoriasis Area and Severity Index score. Results PASI 75 • Standardized average cumulative PASI 75 response over 52 weeks among patients initiating with deucravacitinib was 57.3% compared with 38.2% in patients initiating with apremilast (including 87 patients who continued apremilast after Week 24 and 54 patients who switched to deucravacitinib) (Table 1) — Adjusted AUC 0–52wk [% × weeks] was 2978.72 in the deucravacitinib arm and 1988.06 in the apremilast initiatiors arm — The adjusted difference in AUC 0–52wk was 990.66 (95% CI, 683.37–1297.95); P < 0.001 — The benefit ratio of initiating with deucravacitinib vs apremilast was 1.50 • Figure 2 displays the standardized adjusted cumulative AUC for PASI 75 over 52 weeks sPGA 0/1 • Standardized average cumulative sPGA 0/1 response over 52 weeks among patients initiating with deucravacitinib was 50.2% compared with 31.9% in patients initiating with apremilast (Table 2) — Adjusted AUC 0–52wk [% × weeks] was 2612.82 in the deucravacitinib arm and 1657.13 in the apremilast initiators arm — The adjusted difference in AUC 0–52wk was 955.69 (95% CI, 642.22–1269.16); P < 0.001 — The benefit ratio of initiating with deucravacitinib vs apremilast was 1.58 • Figure 3 displays the standardized adjusted cumulative AUC for sPGA 0/1 over 52 weeks Table 1. Cumulative clinical benefit measured by PASI 75 response over 52 weeks Outcomes Deucravacitinib, n = 332 Apremilast initiators,a n = 168 Difference in estimate (95% CI) P value Benefit ratio Adjusted AUC 0–52wk , % × weeks 2978.72 1988.06 990.66 (683.37–1297.95) < 0.001 1.50 Standardized average cumulative responseb 57.3% 38.2% — — aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. bAUC 0–52wk /maximum AUC 0–52wk . AUC 0–52wk , area under the curve over 52 weeks; CI, confidence interval; PASI 75, 75% improvement from baseline in Psoriasis Area and Severity Index score. Figure 2. Standardized adjusted AUC 0–52wk : PASI 75 0 10 20 30 40 50 60 St an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Deucravacitinib (n = 332) Apremilast initiators (n = 168)a aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. AUC 0–52wk , area under the curve over 52 weeks; PASI 50/75, ≥50%/≥75% improvement from baseline in Psoriasis Area and Severity Index score. Table 2. Cumulative clinical benefit measured by sPGA 0/1 response over 52 weeks Outcomes Deucravacitinib, n = 332 Apremilast initiators,a n = 168 Difference in estimate (95% CI) P value Benefit ratio Adjusted AUC 0–52wk , % × weeks 2612.82 1657.13 955.69 (642.22–1269.16) < 0.001 1.58 Standardized average cumulative responseb 50.2% 31.9% — — aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. bAUC 0–52wk /maximum AUC 0–52wk . AUC 0–52wk , area under the curve over 52 weeks; CI, confidence interval; sPGA 0/1, static Physician Global Assessment score of 0 or 1. Figure 3. Standardized adjusted AUC 0–52wk : sPGA 0/1 Deucravacitinib (n = 332) Apremilast initiators (n = 168)a 0 10 20 30 40 50 60 St an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. AUC 0–52wk , area under the curve over 52 weeks; PASI 50, ≥50% improvement from baseline in Psoriasis Area and Severity Index score; sPGA, static Physician Global Assessment score of 0 or 1. Conclusions • Initiating with deucravacitinib resulted in greater cumulative benefits over 52 weeks than initiating with apremilast — Deucravacitinib initiators spend ≈150% more time in therapeutic response over 1 year compared with apremilast initiators • Initiating with deucravacitinib as the first line rather than switching to deucravacitinib as the second line after failure to respond with apremilast may optimize the clinical benefit that patients receive References 1. Armstrong AW, et al. J Am Acad Dermatol. 2022;S0190-9622 [online ahead of print]. 2. Armstrong AW, et al. [poster] Presented at the American Academy of Dermatology Annual Meeting, March 25–29, 2022, Boston, MA. 3. Armstrong AW, et al. J Dermatolog Treat. 2017;28:200-205. 4. Bushmakin AG, et al. Qual Life Res. 2011;20:491-498. 5. Warren RB, et al. J Eur Acad Dermatol Venereol. 2021;35:450-457. 6. Blauvelt A, et al. J Manag Care Spec Pharm. 2021;27:84-94. Acknowledgments • This study was supported by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Eleanor Bush, MA, of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AWA: 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 • SHP, VP, PN, MJC: Employees of and may own stock options in Bristol Myers Squibb • W-JW, VC: Employees of OPEN Health, which has received consulting fees from Bristol Myers Squibb 1 2 Optimizing the treatment sequence: the cumulative clinical benefi t of treatment initiation with deucravacitinib versus apremilast over 52 weeks in patients with moderate to severe plaque psoriasis from the POETYK PSO-1 trial April W. Armstrong,1 Sang Hee Park,2 Viktor Chirikov,3 Pierre Nicolas,2,4 Wei-Jhih Wang,3 Matthew J. Colombo,2 Vardhaman Patel2 1Keck School of Medicine, University of Southern California, Los Angeles, CA; 2Bristol Myers Squibb, Princeton, NJ; 3OPEN Health, Bethesda, MD; 4Bristol Myers Squibb, Boudry, Switzerland 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 • Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor 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 • In the recent phase 3 clinical trial POETYK PSO-1, patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib, placebo, or apremilast1 — Patients receiving apremilast who did not achieve at least 50% improvement from baseline in Psoriasis Area and Severity Index score (PASI 50) at Week 24 crossed over to deucravacitinib1 • At Week 52, 46.3% of these patients achieved at least 75% improvement from baseline in PASI score (PASI 75), and 42.6% achieved a static Physician Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1)2 — Patients receiving apremilast who achieved PASI 50 at Week 24 continued with apremilast — Patients who received placebo are not represented in this analysis • This study evaluated the cumulative clinical benefit of initiating with deucravacitinib vs apremilast to determine the treatment pathway that provides greater benefit to the patient — The cumulative clinical benefit refl ects the total time patients spend in a state of therapeutic response3 • The results of this study indicate that initiating deucravacitinib as a first-line treatment offers greater benefits over time compared with initiating with apremilast Objective • To evaluate the cumulative clinical benefit of initiating with deucravacitinib vs apremilast from baseline to Week 52 based on data from POETYK PSO-1 Methods • POETYK PSO-1 was a multicenter, randomized, double-blind, placebo- and active comparator–controlled study1 — Patients were aged ≥18 years and had moderate to severe plaque psoriasis (PASI score ≥12, sPGA score ≥3, and body surface area involvement ≥10%) — Coprimary effi cacy endpoints were PASI 75 and sPGA 0/1 — Nonresponder imputation was used for missing data • This post hoc analysis compared data from 2 arms in the POETYK PSO-1 trial (Figure 1) — Deucravacitinib arm: patients initiated with and continued on deucravacitinib, regardless of response status — Apremilast initiators arm: patients initiated with apremilast; at Week 24, PASI 50 responders continued with apremilast while PASI 50 nonresponders crossed over to deucravacitinib • Cumulative clinical benefit from randomization to Week 52 was determined by the total area under the curve of clinical response over 52 weeks (AUC 0–52wk ) in each arm — AUC analysis has been employed to evaluate outcomes over time in clinical trials, as the AUC refl ects the rapidity and durability, as well as the magnitude, of response3-6 • While assessments at discrete time points identify static responses, the AUC approach captures cumulative treatment effects over time — This study determined the AUC using data at a patient level (responder status at each time point over 52 weeks) • Total AUC 0–52wk was calculated separately for each efficacy endpoint, using the trapezoidal rule — Total AUC 0–52wk = 15i=0∑ (Pi+Pi+1)(Ti+1−Ti), where Ti (i = 0, 1, 2, 3, …, 15) denotes the time points of Weeks 0, 1, 2, 4, 8, 12, and 16, then every 4 weeks thereafter through Week 52, and P i denotes the response (yes = 1; no = 0) at each time point, T i • The result was standardized as a percentage of maximum possible AUC 0–52wk (0–5200 [% × weeks]) and aggregated to the population level • Adjusted AUC comparisons between the 2 treatment arms were based on an analysis of covariance (ANCOVA) model, with the following stratification parameters: — Prior use of a biologic treatment (yes/no) — Region (United States, China, Japan, rest of the world [ROW]) — Body weight (<90 kg, ≥90 kg), in the United States and ROW only • Ratios of AUC 0–52wk were calculated, representing the relative cumulative clinical benefit of the 2 treatment pathways for achieving PASI 75 or sPGA 0/1 over the 52-week period Figure 1. Study design comparing data from 2 arms of POETYK PSO-1 Week 0 Week 24 Week 52 Apremilast initiators arm (n = 168) Deucravacitinib arm (n = 332) Initiation of deucravacitinib Continuation of deucravacitinib Initiation of apremilast ≥PASI 50: continuation of apremilast <PASI 50: initiation of deucravacitinib PASI 50, 50% improvement from baseline in Psoriasis Area and Severity Index score. Results PASI 75 • Standardized average cumulative PASI 75 response over 52 weeks among patients initiating with deucravacitinib was 57.3% compared with 38.2% in patients initiating with apremilast (including 87 patients who continued apremilast after Week 24 and 54 patients who switched to deucravacitinib) (Table 1) — Adjusted AUC 0–52wk [% × weeks] was 2978.72 in the deucravacitinib arm and 1988.06 in the apremilast initiatiors arm — The adjusted difference in AUC 0–52wk was 990.66 (95% CI, 683.37–1297.95); P < 0.001 — The benefit ratio of initiating with deucravacitinib vs apremilast was 1.50 • Figure 2 displays the standardized adjusted cumulative AUC for PASI 75 over 52 weeks sPGA 0/1 • Standardized average cumulative sPGA 0/1 response over 52 weeks among patients initiating with deucravacitinib was 50.2% compared with 31.9% in patients initiating with apremilast (Table 2) — Adjusted AUC 0–52wk [% × weeks] was 2612.82 in the deucravacitinib arm and 1657.13 in the apremilast initiators arm — The adjusted difference in AUC 0–52wk was 955.69 (95% CI, 642.22–1269.16); P < 0.001 — The benefit ratio of initiating with deucravacitinib vs apremilast was 1.58 • Figure 3 displays the standardized adjusted cumulative AUC for sPGA 0/1 over 52 weeks Table 1. Cumulative clinical benefit measured by PASI 75 response over 52 weeks Outcomes Deucravacitinib, n = 332 Apremilast initiators,a n = 168 Difference in estimate (95% CI) P value Benefit ratio Adjusted AUC 0–52wk , % × weeks 2978.72 1988.06 990.66 (683.37–1297.95) < 0.001 1.50 Standardized average cumulative responseb 57.3% 38.2% — — aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. bAUC 0–52wk /maximum AUC 0–52wk . AUC 0–52wk , area under the curve over 52 weeks; CI, confidence interval; PASI 75, 75% improvement from baseline in Psoriasis Area and Severity Index score. Figure 2. Standardized adjusted AUC 0–52wk : PASI 75 0 10 20 30 40 50 60 St an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Deucravacitinib (n = 332) Apremilast initiators (n = 168)a aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. AUC 0–52wk , area under the curve over 52 weeks; PASI 50/75, ≥50%/≥75% improvement from baseline in Psoriasis Area and Severity Index score. Table 2. Cumulative clinical benefit measured by sPGA 0/1 response over 52 weeks Outcomes Deucravacitinib, n = 332 Apremilast initiators,a n = 168 Difference in estimate (95% CI) P value Benefit ratio Adjusted AUC 0–52wk , % × weeks 2612.82 1657.13 955.69 (642.22–1269.16) < 0.001 1.58 Standardized average cumulative responseb 50.2% 31.9% — — aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. bAUC 0–52wk /maximum AUC 0–52wk . AUC 0–52wk , area under the curve over 52 weeks; CI, confidence interval; sPGA 0/1, static Physician Global Assessment score of 0 or 1. Figure 3. Standardized adjusted AUC 0–52wk : sPGA 0/1 Deucravacitinib (n = 332) Apremilast initiators (n = 168)a 0 10 20 30 40 50 60 St an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. AUC 0–52wk , area under the curve over 52 weeks; PASI 50, ≥50% improvement from baseline in Psoriasis Area and Severity Index score; sPGA, static Physician Global Assessment score of 0 or 1. Conclusions • Initiating with deucravacitinib resulted in greater cumulative benefits over 52 weeks than initiating with apremilast — Deucravacitinib initiators spend ≈150% more time in therapeutic response over 1 year compared with apremilast initiators • Initiating with deucravacitinib as the first line rather than switching to deucravacitinib as the second line after failure to respond with apremilast may optimize the clinical benefit that patients receive References 1. Armstrong AW, et al. J Am Acad Dermatol. 2022;S0190-9622 [online ahead of print]. 2. Armstrong AW, et al. [poster] Presented at the American Academy of Dermatology Annual Meeting, March 25–29, 2022, Boston, MA. 3. Armstrong AW, et al. J Dermatolog Treat. 2017;28:200-205. 4. Bushmakin AG, et al. Qual Life Res. 2011;20:491-498. 5. Warren RB, et al. J Eur Acad Dermatol Venereol. 2021;35:450-457. 6. Blauvelt A, et al. J Manag Care Spec Pharm. 2021;27:84-94. Acknowledgments • This study was supported by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Eleanor Bush, MA, of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AWA: 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 • SHP, VP, PN, MJC: Employees of and may own stock options in Bristol Myers Squibb • W-JW, VC: Employees of OPEN Health, which has received consulting fees from Bristol Myers Squibb 1 2 Optimizing the treatment sequence: the cumulative clinical benefi t of treatment initiation with deucravacitinib versus apremilast over 52 weeks in patients with moderate to severe plaque psoriasis from the POETYK PSO-1 trial April W. Armstrong,1 Sang Hee Park,2 Viktor Chirikov,3 Pierre Nicolas,2,4 Wei-Jhih Wang,3 Matthew J. Colombo,2 Vardhaman Patel2 1Keck School of Medicine, University of Southern California, Los Angeles, CA; 2Bristol Myers Squibb, Princeton, NJ; 3OPEN Health, Bethesda, MD; 4Bristol Myers Squibb, Boudry, Switzerland 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 • Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor 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 • In the recent phase 3 clinical trial POETYK PSO-1, patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib, placebo, or apremilast1 — Patients receiving apremilast who did not achieve at least 50% improvement from baseline in Psoriasis Area and Severity Index score (PASI 50) at Week 24 crossed over to deucravacitinib1 • At Week 52, 46.3% of these patients achieved at least 75% improvement from baseline in PASI score (PASI 75), and 42.6% achieved a static Physician Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1)2 — Patients receiving apremilast who achieved PASI 50 at Week 24 continued with apremilast — Patients who received placebo are not represented in this analysis • This study evaluated the cumulative clinical benefit of initiating with deucravacitinib vs apremilast to determine the treatment pathway that provides greater benefit to the patient — The cumulative clinical benefit refl ects the total time patients spend in a state of therapeutic response3 • The results of this study indicate that initiating deucravacitinib as a first-line treatment offers greater benefits over time compared with initiating with apremilast Objective • To evaluate the cumulative clinical benefit of initiating with deucravacitinib vs apremilast from baseline to Week 52 based on data from POETYK PSO-1 Methods • POETYK PSO-1 was a multicenter, randomized, double-blind, placebo- and active comparator–controlled study1 — Patients were aged ≥18 years and had moderate to severe plaque psoriasis (PASI score ≥12, sPGA score ≥3, and body surface area involvement ≥10%) — Coprimary effi cacy endpoints were PASI 75 and sPGA 0/1 — Nonresponder imputation was used for missing data • This post hoc analysis compared data from 2 arms in the POETYK PSO-1 trial (Figure 1) — Deucravacitinib arm: patients initiated with and continued on deucravacitinib, regardless of response status — Apremilast initiators arm: patients initiated with apremilast; at Week 24, PASI 50 responders continued with apremilast while PASI 50 nonresponders crossed over to deucravacitinib • Cumulative clinical benefit from randomization to Week 52 was determined by the total area under the curve of clinical response over 52 weeks (AUC 0–52wk ) in each arm — AUC analysis has been employed to evaluate outcomes over time in clinical trials, as the AUC refl ects the rapidity and durability, as well as the magnitude, of response3-6 • While assessments at discrete time points identify static responses, the AUC approach captures cumulative treatment effects over time — This study determined the AUC using data at a patient level (responder status at each time point over 52 weeks) • Total AUC 0–52wk was calculated separately for each efficacy endpoint, using the trapezoidal rule — Total AUC 0–52wk = 15i=0∑ (Pi+Pi+1)(Ti+1−Ti), where Ti (i = 0, 1, 2, 3, …, 15) denotes the time points of Weeks 0, 1, 2, 4, 8, 12, and 16, then every 4 weeks thereafter through Week 52, and P i denotes the response (yes = 1; no = 0) at each time point, T i • The result was standardized as a percentage of maximum possible AUC 0–52wk (0–5200 [% × weeks]) and aggregated to the population level • Adjusted AUC comparisons between the 2 treatment arms were based on an analysis of covariance (ANCOVA) model, with the following stratification parameters: — Prior use of a biologic treatment (yes/no) — Region (United States, China, Japan, rest of the world [ROW]) — Body weight (<90 kg, ≥90 kg), in the United States and ROW only • Ratios of AUC 0–52wk were calculated, representing the relative cumulative clinical benefit of the 2 treatment pathways for achieving PASI 75 or sPGA 0/1 over the 52-week period Figure 1. Study design comparing data from 2 arms of POETYK PSO-1 Week 0 Week 24 Week 52 Apremilast initiators arm (n = 168) Deucravacitinib arm (n = 332) Initiation of deucravacitinib Continuation of deucravacitinib Initiation of apremilast ≥PASI 50: continuation of apremilast <PASI 50: initiation of deucravacitinib PASI 50, 50% improvement from baseline in Psoriasis Area and Severity Index score. Results PASI 75 • Standardized average cumulative PASI 75 response over 52 weeks among patients initiating with deucravacitinib was 57.3% compared with 38.2% in patients initiating with apremilast (including 87 patients who continued apremilast after Week 24 and 54 patients who switched to deucravacitinib) (Table 1) — Adjusted AUC 0–52wk [% × weeks] was 2978.72 in the deucravacitinib arm and 1988.06 in the apremilast initiatiors arm — The adjusted difference in AUC 0–52wk was 990.66 (95% CI, 683.37–1297.95); P < 0.001 — The benefit ratio of initiating with deucravacitinib vs apremilast was 1.50 • Figure 2 displays the standardized adjusted cumulative AUC for PASI 75 over 52 weeks sPGA 0/1 • Standardized average cumulative sPGA 0/1 response over 52 weeks among patients initiating with deucravacitinib was 50.2% compared with 31.9% in patients initiating with apremilast (Table 2) — Adjusted AUC 0–52wk [% × weeks] was 2612.82 in the deucravacitinib arm and 1657.13 in the apremilast initiators arm — The adjusted difference in AUC 0–52wk was 955.69 (95% CI, 642.22–1269.16); P < 0.001 — The benefit ratio of initiating with deucravacitinib vs apremilast was 1.58 • Figure 3 displays the standardized adjusted cumulative AUC for sPGA 0/1 over 52 weeks Table 1. Cumulative clinical benefit measured by PASI 75 response over 52 weeks Outcomes Deucravacitinib, n = 332 Apremilast initiators,a n = 168 Difference in estimate (95% CI) P value Benefit ratio Adjusted AUC 0–52wk , % × weeks 2978.72 1988.06 990.66 (683.37–1297.95) < 0.001 1.50 Standardized average cumulative responseb 57.3% 38.2% — — aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. bAUC 0–52wk /maximum AUC 0–52wk . AUC 0–52wk , area under the curve over 52 weeks; CI, confidence interval; PASI 75, 75% improvement from baseline in Psoriasis Area and Severity Index score. Figure 2. Standardized adjusted AUC 0–52wk : PASI 75 0 10 20 30 40 50 60 St an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Deucravacitinib (n = 332) Apremilast initiators (n = 168)a aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. AUC 0–52wk , area under the curve over 52 weeks; PASI 50/75, ≥50%/≥75% improvement from baseline in Psoriasis Area and Severity Index score. Table 2. Cumulative clinical benefit measured by sPGA 0/1 response over 52 weeks Outcomes Deucravacitinib, n = 332 Apremilast initiators,a n = 168 Difference in estimate (95% CI) P value Benefit ratio Adjusted AUC 0–52wk , % × weeks 2612.82 1657.13 955.69 (642.22–1269.16) < 0.001 1.58 Standardized average cumulative responseb 50.2% 31.9% — — aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. bAUC 0–52wk /maximum AUC 0–52wk . AUC 0–52wk , area under the curve over 52 weeks; CI, confidence interval; sPGA 0/1, static Physician Global Assessment score of 0 or 1. Figure 3. Standardized adjusted AUC 0–52wk : sPGA 0/1 Deucravacitinib (n = 332) Apremilast initiators (n = 168)a 0 10 20 30 40 50 60 St an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. AUC 0–52wk , area under the curve over 52 weeks; PASI 50, ≥50% improvement from baseline in Psoriasis Area and Severity Index score; sPGA, static Physician Global Assessment score of 0 or 1. Conclusions • Initiating with deucravacitinib resulted in greater cumulative benefits over 52 weeks than initiating with apremilast — Deucravacitinib initiators spend ≈150% more time in therapeutic response over 1 year compared with apremilast initiators • Initiating with deucravacitinib as the first line rather than switching to deucravacitinib as the second line after failure to respond with apremilast may optimize the clinical benefit that patients receive References 1. Armstrong AW, et al. J Am Acad Dermatol. 2022;S0190-9622 [online ahead of print]. 2. Armstrong AW, et al. [poster] Presented at the American Academy of Dermatology Annual Meeting, March 25–29, 2022, Boston, MA. 3. Armstrong AW, et al. J Dermatolog Treat. 2017;28:200-205. 4. Bushmakin AG, et al. Qual Life Res. 2011;20:491-498. 5. Warren RB, et al. J Eur Acad Dermatol Venereol. 2021;35:450-457. 6. Blauvelt A, et al. J Manag Care Spec Pharm. 2021;27:84-94. Acknowledgments • This study was supported by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Eleanor Bush, MA, of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AWA: 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 • SHP, VP, PN, MJC: Employees of and may own stock options in Bristol Myers Squibb • W-JW, VC: Employees of OPEN Health, which has received consulting fees from Bristol Myers Squibb 1 2 Optimizing the treatment sequence: the cumulative clinical benefi t of treatment initiation with deucravacitinib versus apremilast over 52 weeks in patients with moderate to severe plaque psoriasis from the POETYK PSO-1 trial April W. Armstrong,1 Sang Hee Park,2 Viktor Chirikov,3 Pierre Nicolas,2,4 Wei-Jhih Wang,3 Matthew J. Colombo,2 Vardhaman Patel2 1Keck School of Medicine, University of Southern California, Los Angeles, CA; 2Bristol Myers Squibb, Princeton, NJ; 3OPEN Health, Bethesda, MD; 4Bristol Myers Squibb, Boudry, Switzerland 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 • Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor 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 • In the recent phase 3 clinical trial POETYK PSO-1, patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib, placebo, or apremilast1 — Patients receiving apremilast who did not achieve at least 50% improvement from baseline in Psoriasis Area and Severity Index score (PASI 50) at Week 24 crossed over to deucravacitinib1 • At Week 52, 46.3% of these patients achieved at least 75% improvement from baseline in PASI score (PASI 75), and 42.6% achieved a static Physician Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1)2 — Patients receiving apremilast who achieved PASI 50 at Week 24 continued with apremilast — Patients who received placebo are not represented in this analysis • This study evaluated the cumulative clinical benefit of initiating with deucravacitinib vs apremilast to determine the treatment pathway that provides greater benefit to the patient — The cumulative clinical benefit refl ects the total time patients spend in a state of therapeutic response3 • The results of this study indicate that initiating deucravacitinib as a first-line treatment offers greater benefits over time compared with initiating with apremilast Objective • To evaluate the cumulative clinical benefit of initiating with deucravacitinib vs apremilast from baseline to Week 52 based on data from POETYK PSO-1 Methods • POETYK PSO-1 was a multicenter, randomized, double-blind, placebo- and active comparator–controlled study1 — Patients were aged ≥18 years and had moderate to severe plaque psoriasis (PASI score ≥12, sPGA score ≥3, and body surface area involvement ≥10%) — Coprimary effi cacy endpoints were PASI 75 and sPGA 0/1 — Nonresponder imputation was used for missing data • This post hoc analysis compared data from 2 arms in the POETYK PSO-1 trial (Figure 1) — Deucravacitinib arm: patients initiated with and continued on deucravacitinib, regardless of response status — Apremilast initiators arm: patients initiated with apremilast; at Week 24, PASI 50 responders continued with apremilast while PASI 50 nonresponders crossed over to deucravacitinib • Cumulative clinical benefit from randomization to Week 52 was determined by the total area under the curve of clinical response over 52 weeks (AUC 0–52wk ) in each arm — AUC analysis has been employed to evaluate outcomes over time in clinical trials, as the AUC refl ects the rapidity and durability, as well as the magnitude, of response3-6 • While assessments at discrete time points identify static responses, the AUC approach captures cumulative treatment effects over time — This study determined the AUC using data at a patient level (responder status at each time point over 52 weeks) • Total AUC 0–52wk was calculated separately for each efficacy endpoint, using the trapezoidal rule — Total AUC 0–52wk = 15i=0∑ (Pi+Pi+1)(Ti+1−Ti), where Ti (i = 0, 1, 2, 3, …, 15) denotes the time points of Weeks 0, 1, 2, 4, 8, 12, and 16, then every 4 weeks thereafter through Week 52, and P i denotes the response (yes = 1; no = 0) at each time point, T i • The result was standardized as a percentage of maximum possible AUC 0–52wk (0–5200 [% × weeks]) and aggregated to the population level • Adjusted AUC comparisons between the 2 treatment arms were based on an analysis of covariance (ANCOVA) model, with the following stratification parameters: — Prior use of a biologic treatment (yes/no) — Region (United States, China, Japan, rest of the world [ROW]) — Body weight (<90 kg, ≥90 kg), in the United States and ROW only • Ratios of AUC 0–52wk were calculated, representing the relative cumulative clinical benefit of the 2 treatment pathways for achieving PASI 75 or sPGA 0/1 over the 52-week period Figure 1. Study design comparing data from 2 arms of POETYK PSO-1 Week 0 Week 24 Week 52 Apremilast initiators arm (n = 168) Deucravacitinib arm (n = 332) Initiation of deucravacitinib Continuation of deucravacitinib Initiation of apremilast ≥PASI 50: continuation of apremilast <PASI 50: initiation of deucravacitinib PASI 50, 50% improvement from baseline in Psoriasis Area and Severity Index score. Results PASI 75 • Standardized average cumulative PASI 75 response over 52 weeks among patients initiating with deucravacitinib was 57.3% compared with 38.2% in patients initiating with apremilast (including 87 patients who continued apremilast after Week 24 and 54 patients who switched to deucravacitinib) (Table 1) — Adjusted AUC 0–52wk [% × weeks] was 2978.72 in the deucravacitinib arm and 1988.06 in the apremilast initiatiors arm — The adjusted difference in AUC 0–52wk was 990.66 (95% CI, 683.37–1297.95); P < 0.001 — The benefit ratio of initiating with deucravacitinib vs apremilast was 1.50 • Figure 2 displays the standardized adjusted cumulative AUC for PASI 75 over 52 weeks sPGA 0/1 • Standardized average cumulative sPGA 0/1 response over 52 weeks among patients initiating with deucravacitinib was 50.2% compared with 31.9% in patients initiating with apremilast (Table 2) — Adjusted AUC 0–52wk [% × weeks] was 2612.82 in the deucravacitinib arm and 1657.13 in the apremilast initiators arm — The adjusted difference in AUC 0–52wk was 955.69 (95% CI, 642.22–1269.16); P < 0.001 — The benefit ratio of initiating with deucravacitinib vs apremilast was 1.58 • Figure 3 displays the standardized adjusted cumulative AUC for sPGA 0/1 over 52 weeks Table 1. Cumulative clinical benefit measured by PASI 75 response over 52 weeks Outcomes Deucravacitinib, n = 332 Apremilast initiators,a n = 168 Difference in estimate (95% CI) P value Benefit ratio Adjusted AUC 0–52wk , % × weeks 2978.72 1988.06 990.66 (683.37–1297.95) < 0.001 1.50 Standardized average cumulative responseb 57.3% 38.2% — — aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. bAUC 0–52wk /maximum AUC 0–52wk . AUC 0–52wk , area under the curve over 52 weeks; CI, confidence interval; PASI 75, 75% improvement from baseline in Psoriasis Area and Severity Index score. Figure 2. Standardized adjusted AUC 0–52wk : PASI 75 0 10 20 30 40 50 60 St an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Deucravacitinib (n = 332) Apremilast initiators (n = 168)a aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. AUC 0–52wk , area under the curve over 52 weeks; PASI 50/75, ≥50%/≥75% improvement from baseline in Psoriasis Area and Severity Index score. Table 2. Cumulative clinical benefit measured by sPGA 0/1 response over 52 weeks Outcomes Deucravacitinib, n = 332 Apremilast initiators,a n = 168 Difference in estimate (95% CI) P value Benefit ratio Adjusted AUC 0–52wk , % × weeks 2612.82 1657.13 955.69 (642.22–1269.16) < 0.001 1.58 Standardized average cumulative responseb 50.2% 31.9% — — aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. bAUC 0–52wk /maximum AUC 0–52wk . AUC 0–52wk , area under the curve over 52 weeks; CI, confidence interval; sPGA 0/1, static Physician Global Assessment score of 0 or 1. Figure 3. Standardized adjusted AUC 0–52wk : sPGA 0/1 Deucravacitinib (n = 332) Apremilast initiators (n = 168)a 0 10 20 30 40 50 60 St an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aAmong patients initiating with apremilast, 87 achieved PASI 50 at Week 24 and continued receiving apremilast, and 54 did not achieve PASI 50 and switched to deucravacitinib. AUC 0–52wk , area under the curve over 52 weeks; PASI 50, ≥50% improvement from baseline in Psoriasis Area and Severity Index score; sPGA, static Physician Global Assessment score of 0 or 1. Conclusions • Initiating with deucravacitinib resulted in greater cumulative benefits over 52 weeks than initiating with apremilast — Deucravacitinib initiators spend ≈150% more time in therapeutic response over 1 year compared with apremilast initiators • Initiating with deucravacitinib as the first line rather than switching to deucravacitinib as the second line after failure to respond with apremilast may optimize the clinical benefit that patients receive References 1. Armstrong AW, et al. J Am Acad Dermatol. 2022;S0190-9622 [online ahead of print]. 2. Armstrong AW, et al. [poster] Presented at the American Academy of Dermatology Annual Meeting, March 25–29, 2022, Boston, MA. 3. Armstrong AW, et al. J Dermatolog Treat. 2017;28:200-205. 4. Bushmakin AG, et al. Qual Life Res. 2011;20:491-498. 5. Warren RB, et al. J Eur Acad Dermatol Venereol. 2021;35:450-457. 6. Blauvelt A, et al. J Manag Care Spec Pharm. 2021;27:84-94. Acknowledgments • This study was supported by Bristol Myers Squibb • Medical writing and editorial assistance was provided by Eleanor Bush, MA, of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb Disclosures • AWA: 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 • SHP, VP, PN, MJC: Employees of and may own stock options in Bristol Myers Squibb • W-JW, VC: Employees of OPEN Health, which has received consulting fees from Bristol Myers Squibb 1 2