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

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• 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 response [3][4][5][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 = 15 i=0 ∑ (P i +P i+1 )(T i+1 −T i ), where T i (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:  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  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. AUC0-52wk, area under the curve over 52 weeks; PASI 50/75, ≥50%/≥75% improvement from baseline in Psoriasis Area and Severity Index score.   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. AUC0-52wk, 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

Methods
• POETYK PSO-1 was a multicenter, randomized, double-blind, placebo-and active comparator-controlled study 1 -Patients were aged ≥18 years and had moderate to severe plaque psoriasis (PASI score ≥12, sPGA score ≥3, and body surface area involvement ≥10%) -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 response [3][4][5][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  Week 0 Week 24 Week 52  Figure 3 displays the standardized adjusted cumulative AUC for sPGA 0/1 over 52 weeks

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

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

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