Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: correlations between patient-reported outcomes and clinical responses in the phase 3 clinical trials POETYK PSO-1 and POETYK PSO-2

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Week 16 Week 24 Week 52 DLQI change from baseline a PASI <50 PASI 50-74 PASI 75-89 PASI 90-99 PASI 100 aThe mean baseline DLQI score (SD) among all patients in the study population was 12.0 (6.7). DLQI, Dermatology Life Quality Index; PASI 50-100, 50%-100% improvement from baseline Psoriasis Area and Severity Index score. Week 16 Week 24 Week 52 PSSD change from baseline sPGA +1 sPGA 0 sPGA -1 sPGA -2 sPGA -3 or more aAt baseline, 1345 patients in the total study population had an sPGA score of 3, and 340 had an sPGA score of 4. One patient had an sPGA score of 2; this patient was randomized but not treated. The mean baseline PSSD total score (SD) was 54. 4   Week 52 DLQI change from baseline sPGA +1 sPGA 0 sPGA -1 sPGA -2 sPGA -3 or more aAt baseline, 1345 patients in the total study population had an sPGA score of 3 and 340 had an sPGA score of 4. One patient had an sPGA score of 2; this patient was randomized but not treated. The mean baseline DLQI score (SD) among all patients in the study population was 12.0 (6.7). DLQI, Dermatology Life Quality Index; sPGA, static Physician's Global Assessment.

PSSD Response by Clinical Response
• At Week 16, PSSD total score response (≥25-point reduction from baseline) was reported by 64.8% and 65.3% of all patients across both trials who achieved PASI 75 (356/549) and/or sPGA 0/1 (330/505), respectively ( Table 1) -Greater proportions of patients who received deucravacitinib and achieved clinical response reported PSSD total score response (68.6% of patients who achieved PASI 75 and 68.7% of patients who achieved sPGA 0/1) compared with patients who received placebo (31.3% of patients who achieved PASI 75 and 37.0% of patients who achieved sPGA 0/1) ( Table 1) -On the PSSD itch item, meaningful improvement (≥2 points) was reported by 80.8% of patients receiving deucravacitinib who achieved PASI 75 and 80.1% of deucravacitinib-treated patients who achieved sPGA 0/1, compared with 43.8% of patients receiving placebo who achieved PASI 75 and 48.1% of placebo-treated patients who achieved sPGA 0/1 (Figure 5) • At Week 16, 27.9% and 29.8% of all patients across both trials who did not achieve PASI 75 (188/674) and/or did not achieve sPGA 0/1 (214/718), respectively, nonetheless reported PSSD total score response -Greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported PSSD total score response (41.8% of patients who did not achieve PASI 75 and 44.1% of patients who did not achieve sPGA 0/1) compared with patients who received placebo (10.4% of patients who did not achieve PASI 75 and 10.3% who did not achieve sPGA 0/1) -On the PSSD itch item, meaningful improvement was reported by 54.9% of patients receiving deucravacitinib who did not achieve PASI 75 compared with 22.0% of patients receiving placebo who did not achieve PASI 75    • PSSD -Patient rated -5 skin symptoms (itch, tightness, burning, stinging, and pain) and 6 skin signs (dryness, cracking, scaling, shedding/fl aking, redness, and bleeding) associated with psoriasis were rated 0 (absent) to 10 (worst imaginable); averages within each domain were multiplied by 10, then averaged across both domains to obtain a total score -Range: 0-100, with higher scores indicating heavier disease burden • At Week 16, change from baseline in sPGA score was correlated with changes in the PSSD total score (r s = 0.496) and DLQI total score (r s = 0.380) in the total study population • Higher PASI or sPGA response was associated with greater PSSD and DLQI responses at Weeks 16, 24, and 52 in the total study population (Figures 1-4  Week 16 Week 24 Week 52 DLQI change from baseline a PASI <50 PASI 50-74 PASI 75-89 PASI 90-99 PASI 100 aThe mean baseline DLQI score (SD) among all patients in the study population was 12.0 (6.7). DLQI, Dermatology Life Quality Index; PASI 50-100, 50%-100% improvement from baseline Psoriasis Area and Severity Index score. Week 52 DLQI change from baseline sPGA +1 sPGA 0 sPGA -1 sPGA -2 sPGA -3 or more aAt baseline, 1345 patients in the total study population had an sPGA score of 3 and 340 had an sPGA score of 4. One patient had an sPGA score of 2; this patient was randomized but not treated. The mean baseline DLQI score (SD) among all patients in the study population was 12.0 (6.7). DLQI, Dermatology Life Quality Index; sPGA, static Physician's Global Assessment.

PSSD Response by Clinical Response
• At Week 16, PSSD total score response (≥25-point reduction from baseline) was reported by 64.8% and 65.3% of all patients across both trials who achieved PASI 75 (356/549) and/or sPGA 0/1 (330/505), respectively ( Table 1) -Greater proportions of patients who received deucravacitinib and achieved clinical response reported PSSD total score response (68.6% of patients who achieved PASI 75 and 68.7% of patients who achieved sPGA 0/1) compared with patients who received placebo (31.3% of patients who achieved PASI 75 and 37.0% of patients who achieved sPGA 0/1) ( Table 1) -On the PSSD itch item, meaningful improvement (≥2 points) was reported by 80.8% of patients receiving deucravacitinib who achieved PASI 75 and 80.1% of deucravacitinib-treated patients who achieved sPGA 0/1, compared with 43.8% of patients receiving placebo who achieved PASI 75 and 48.1% of placebo-treated patients who achieved sPGA 0/1 (Figure 5) • At Week 16, 27.9% and 29.8% of all patients across both trials who did not achieve PASI 75 (188/674) and/or did not achieve sPGA 0/1 (214/718), respectively, nonetheless reported PSSD total score response -Greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported PSSD total score response (41.8% of patients who did not achieve PASI 75 and 44.1% of patients who did not achieve sPGA 0/1) compared with patients who received placebo (10.4% of patients who did not achieve PASI 75 and 10.3% who did not achieve sPGA 0/1) -On the PSSD itch item, meaningful improvement was reported by 54.9% of patients receiving deucravacitinib who did not achieve PASI 75 compared with 22.0% of patients receiving placebo who did not achieve PASI 75 Table 1   • At Week 16, 54.7% and 57.3% of all patients across both trials who did not achieve PASI 75 (444/811) and/or did not achieve sPGA 0/1 (501/874), respectively, nonetheless reported DLQI response -Greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported meaningful DLQI improvement (67.1% of patients who did not achieve PASI 75 and 70.8% of patients who did not achieve sPGA 0/1) compared with patients who received placebo (40.5% of patients who did not achieve PASI 75 and 41.7% who did not achieve sPGA 0/1)

Synopsis
• In the phase 3 clinical trials POETYK PSO-1 and PSO-2, deucravacitinib was compared for effi cacy and safety with placebo and apremilast in the treatment of patients with moderate to severe plaque psoriasis 1 -Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 (TYK2) 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 each clinical trial, greater proportions of patients who received deucravacitinib achieved ≥75% reduction from baseline in the Psoriasis Area and Severity Index score (PASI 75) 1 and static Physician's Global Assessment scores of 0 or 1 (sPGA 0/1), 1 and showed meaningful improvements on Psoriasis Symptoms and Signs Diary (PSSD) total scores (≥25 points) 2 and Dermatology Life Quality Index (DLQI) total scores (≥4 points) 3

Correlations between clinical and PRO measures
• At Week 16, change from baseline in relative PASI score was correlated with changes in the PSSD total score (Spearman's rank correlation coeffi cient [r s ] = 0.536) and DLQI total score (r s = 0.421) in the total study population • At Week 16, change from basel (r s = 0.496) and DLQI total scor • Higher PASI or sPGA response w 52 in the total study population  n signs (dryness, cracking, asis were rated 0 (absent) to y 10, then averaged across both ts' lives se ith changes in the PSSD total al score (r s = 0.421) in the total • At Week 16, change from baseline in sPGA score was correlated with changes in the PSSD total score (r s = 0.496) and DLQI total score (r s = 0.380) in the total study population • Higher PASI or sPGA response was associated with greater PSSD and DLQI responses at Weeks 16, 24, and 52 in the total study population (Figures 1-4)

oup (treatment arms
Week 52 sPGA -3 or more ; this patient was randomized but not treated. The mean Week 52 DLQI change from baseline sPGA +1 sPGA 0 sPGA -1 sPGA -2 sPGA -3 or more a At baseline, 1345 patients in the total study population had an sPGA score of 3 and 340 had an sPGA score of 4. One patient had an sPGA score of 2; this patient was randomized but not treated. The mean baseline DLQI score (SD) among all patients in the study population was 12.0 (6.7). DLQI, Dermatology Life Quality Index; sPGA, static Physician's Global Assessment.

PSSD Response by Clinical Response
• At Week 16, PSSD total score response (≥25-point reduction from baseline) was reported by 64.8% and 65.3% of all patients across both trials who achieved PASI 75 (356/549) and/or sPGA 0/1 (330/505), respectively ( Table 1) -Greater proportions of patients who received deucravacitinib and achieved clinical response reported PSSD total score response (68.6% of patients who achieved PASI 75 and 68.7% of patients who achieved sPGA 0/1) compared with patients who received placebo (31.3% of patients who achieved PASI 75 and 37.0% of patients who achieved sPGA 0/1) ( Table 1) -On the PSSD itch item, meaningful improvement (≥2 points) was reported by 80.8% of patients receiving deucravacitinib who achieved PASI 75 and 80.1% of deucravacitinib-treated patients who achieved sPGA 0/1, compared with 43.8% of patients receiving placebo who achieved PASI 75 and 48.1% of placebo-treated patients who achieved sPGA 0/1 (Figure 5) • At Week 16, 27.9% and 29.8% of all patients across both trials who did not achieve PASI 75 (188/674) and/or did not achieve sPGA 0/1 (214/718), respectively, nonetheless reported PSSD total score response -Greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported PSSD total score response (41.8% of patients who did not achieve PASI 75 and 44.1% of patients who did not achieve sPGA 0/1) compared with patients who received placebo (10.4% of patients who did not achieve PASI 75 and 10.3% who did not achieve sPGA 0/1) -On the PSSD itch item, meaningful improvement was reported by 54.9% of patients receiving deucravacitinib who did not achieve PASI 75 compared with 22.0% of patients receiving placebo who did not achieve PASI 75 Table 1   a Denominators include patients who achieved clinical response and completed ≥1 PSSD item at baseline and ≥1 PSSD item at a post-baseline visit. PASI 75, 75% reduction from baseline in Psoriasis Area and Severity Index score; PSSD, Psoriasis Symptoms and Signs Diary; sPGA 0/1, static Physician's Global Assessment score of 0 or 1.

DLQI Response by Clinical Response
• At Week 16, DLQI response (≥4-point reduction from baseline) was reported by 83.3% and 82.5% of all patients across both trials who achieved PASI 75 (553/664) and/or sPGA 0/1 (496/601), respectively ( Table 2) -Greater proportions of patients who received deucravacitinib and achieved clinical response reported meaningful DLQI improvement (84.7% of patients who achieved PASI 75 and 83.3% of patients who achieved sPGA 0/1) compared with patients who received placebo (72.7% of patients who achieved PASI 75 and 70.6% of patients who achieved sPGA 0/1) • At Week 16, 54.7% and 57.3% of all patients across both trials who did not achieve PASI 75 (444/811) and/or did not achieve sPGA 0/1 (501/874), respectively, nonetheless reported DLQI response -Greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported meaningful DLQI improvement (67.1% of patients who did not achieve PASI 75 and 70.8% of patients who did not achieve sPGA 0/1) compared with patients who received placebo (40.5% of patients who did not achieve PASI 75 and 41.7% who did not achieve sPGA 0/1) Global Assessment scores of 0 or 1 (sPGA 0/1), 1 and showed meaningful improvements on Psoriasis Symptoms and Signs Diary (PSSD) total scores (≥25 points) 2 and Dermatology Life Quality Index (DLQI) total scores (≥4 points) 3 compared with patients receiving placebo or apremilast • In this post hoc analysis of data pooled from both trials, clinical and patient-reported outcomes (PROs) were found to be correlated • When analyzed by the deucravacitinib or placebo treatment arm, greater proportions of patients who received deucravacitinib reported symptom reduction and improved quality of life, both in patients who did and who did not achieve PASI 75 and sPGA 0/1 responses

Objective
• To explore the correlations between responses on clinical and PRO measures in pooled data from POETYK PSO-1 and PSO-2

Methods
• In POETYK PSO-1 (N = 666) and PSO-2 (N = 1020) adults (aged ≥18 years) with moderate to severe psoriasis were randomized 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily -At Week 16 in each trial, patients who received placebo crossed over to deucravacitinib • Using data pooled from both trials, we evaluated the correlation between responses measured by PASI and sPGA on one hand, and the PRO measures PSSD (≥25 points) 2  • PSSD -Patient rated -5 skin symptoms (itch, tightness, burning, stinging, and pain) and 6 skin signs (dryness, cracking, scaling, shedding/fl aking, redness, and bleeding) associated with psoriasis were rated 0 (absent) to 10 (worst imaginable); averages within each domain were multiplied by 10, then averaged across both domains to obtain a total score  DLQI change fro sPGA +1 sPGA 0 sPGA -1 sPGA -2 sPGA -3 or more aAt baseline, 1345 patients in the total study population had an sPGA score of 3 and 340 had an sPGA score of 4. One patient had an sPGA score of 2; this patient was randomized but not treated. The mean baseline DLQI score (SD) among all patients in the study population was 12.0 (6.7). DLQI, Dermatology Life Quality Index; sPGA, static Physician's Global Assessment.

PSSD Response by Clinical Response
• At Week 16, PSSD total score response (≥25-point reduction from baseline) was reported by 64.8% and 65.3% of all patients across both trials who achieved PASI 75 (356/549) and/or sPGA 0/1 (330/505), respectively (Table 1) -Greater proportions of patients who received deucravacitinib and achieved clinical response reported PSSD total score response (68.6% of patients who achieved PASI 75 and 68.7% of patients who achieved sPGA 0/1) compared with patients who received placebo (31.3% of patients who achieved PASI 75 and 37.0% of patients who achieved sPGA 0/1) ( Table 1) -On the PSSD itch item, meaningful improvement (≥2 points) was reported by 80.8% of patients receiving deucravacitinib who achieved PASI 75 and 80.1% of deucravacitinib-treated patients who achieved sPGA 0/1, compared with 43.8% of patients receiving placebo who achieved PASI 75 and 48.1% of placebo-treated patients who achieved sPGA 0/1 (Figure 5) • At Week 16, 27.9% and 29.8% of all patients across both trials who did not achieve PASI 75 (188/674) and/or did not achieve sPGA 0/1 (214/718), respectively, nonetheless reported PSSD total score response -Greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported PSSD total score response (41.8% of patients who did not achieve PASI 75 and 44.1% of patients who did not achieve sPGA 0/1) compared with patients who received placebo (10.4% of patients who did not achieve PASI 75 and 10.3% who did not achieve sPGA 0/1) -On the PSSD itch item, meaningful improvement was reported by 54.9% of patients receiving deucravacitinib who did not achieve PASI 75 compared with 22.0% of patients receiving placebo who did not achieve PASI 75 Table 1   aDenominators include patients who achieved clinical response and completed ≥1 PSSD item at baseline and ≥1 PSSD item at a post-baseline visit. PASI 75, 75% reduction from baseline in Psoriasis Area and Severity Index score; PSSD, Psoriasis Symptoms and Signs Diary; sPGA 0/1, static Physician's Global Assessment score of 0 or 1. and/or did not achieve sPGA 0/1 (501/874), respectively, nonetheless reported DLQI response -Greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported meaningful DLQI improvement (67.1% of patients who did not achieve PASI 75 and 70.8% of patients who did not achieve sPGA 0/1) compared with patients who received placebo (40.5% of patients who did not achieve PASI 75 and 41.7% who did not achieve sPGA 0/1) aThe denominator includes the patients who achieved clinical response and completed ≥1 DLQI item at baseline and ≥1 DLQI item at a post-baseline visit. bTotal denominator includes patients who received apremilast. DLQI, Dermatology Life Quality Index; PASI 75, ≥75% improvement from baseline in Psoriasis Area and Severity Index score; sPGA 0/1, static Physician's Global Assessment score of 0 or 1.

Conclusions
• Psoriasis skin clearance, symptom reduction, and improved patient quality of life were correlated in the POETYK PSO-1 and PSO-2 trials -This correlation is consistent with that determined in other studies [4][5][6][7] • Higher clinical response was associated with greater PRO measure response • PRO measures capture patient-perceived treatment benefi ts that may not be ascertained by measuring rates of skin clearance with clinical assessments alone 4 -Psoriasis bears symptoms, such as pruritus, for which there are no validated objective measures, 8 or which are best assessed by patients themselves 9 in order to evaluate treatment effi cacy -Among patients who achieved PASI 75 at Week 16, 80.8% of patients who received deucravacitinib reported meaningful itch improvement on the PSSD compared with 43.8% of patients who received placebo • Among patients with and without clinical response, greater proportions of patients treated with deucravacitinib recorded improvement in their self-reported symptoms, signs, and quality of life compared with patients treated with placebo