Association Between Achievement of Clinical Disease Control and Improvement in Patient-Reported Outcomes and Quality of Life in Patients With Psoriatic Arthritis in the Phase 3 SELECT-PsA 1 and 2 Randomized Controlled Trials

Abstract

Objective: We explored the relationship between achievement of clinical disease control and improvements in and normative values for patient-reported outcomes (PROs), including quality of life (QoL) measures, in patients with psoriatic arthritis (PsA).

Methods: This was a post hoc analysis of 104-week data from the SELECT-PsA 1 and 2 trials in adults with PsA and inadequate response to one or more conventional synthetic (SELECT-PsA 1) or biologic (SELECT-PsA 2) disease-modifying antirheumatic drug. Patients were initially randomized to upadacitinib 15 mg once daily (QD) to placebo switched to upadacitinib 15 mg QD at week 24 or to adalimumab 40 mg every other week (SELECT-PsA 1 only), and data were pooled across treatments and analyzed. We evaluated several clinical disease control measures (minimal disease activity [MDA]; very low disease activity [VLDA]; and low disease activity [LDA] and/or remission by Disease Activity in Psoriatic Arthritis [DAPSA], Psoriatic Arthritis Disease Activity Score [PASDAS], and Routine Assessment of Patient Index Data 3 [RAPID3]) and examined their associations with improvements and normative values for various PROs.

Results: A total of 1,069 and 317 patients were analyzed for SELECT-PsA 1 and 2, respectively. In both studies, responders (patients who achieved MDA or VLDA, and DAPSA, PASDAS, and RAPID3 LDA or remission) at week 104 achieved more marked changes from baseline, and more responders achieved normative values in PROs compared with nonresponders (most nominal P < 0.0001). Furthermore, numerically larger proportions of responders achieved minimal clinically important differences across PROs compared with nonresponders in both studies. In addition, patients who achieved MDA or VLDA were more likely to achieve DAPSA, PASDAS, and RAPID3 LDA or remission (all nominal P < 0.0001) for upadacitinib 15 mg QD and when treatment arms were pooled.

Conclusion: Patients with PsA who achieve clinical disease control are more likely to achieve improvements and normative values in PROs and QoL measures, which reinforces disease control as a treatment target.

Figure 1

Proportion of patients achieving (A) MDA and VLDA, (B) DAPSA LDA and REM, (C) PASDAS LDA and REM, and (D) RAPID3 LDA and REM by treatment arm in SELECT‐PsA 1 and SELECT‐PsA 2 at week 104 (AO data). MDA response was defined as achievement of ≥5 of the 7 MDA components. VLDA response was defined as achievement of all seven MDA components. DAPSA LDA and REM were defined as ≤14 and ≤4, respectively. PASDAS LDA and REM were defined as ≤3.2 and ≤1.9, respectively. RAPID3 LDA and REM were defined as ≤6 and ≤3, respectively. ADA, adalimumab; AO, as observed; DAPSA, Disease Activity in Psoriatic Arthritis; EOW, every other week; LDA, low disease activity; MDA, minimal disease activity; PASDAS, Psoriatic Arthritis Disease Activity Score; PBO, placebo; PsA, psoriatic arthritis; QD, once daily; REM, remission; UPA, upadacitinib; VLDA, very low disease activity.

Figure 2

Proportion of patients achieving MDA components among (A) MDA responders and (B) MDA nonresponders by treatment arm in SELECT‐PsA 1 and SELECT‐PsA 2 at week 104 (AO data). MDA response was defined as achievement of ≥5 of the 7 MDA components. ADA, adalimumab; AO, as observed; BSA‐PS, psoriasis body surface area; EOW, every other week; HAQ‐DI, Health Assessment Questionnaire‐Disability Index; LEI, Leeds Enthesitis Index; MDA, minimal disease activity; PASI, Psoriasis Area and Severity Index; PtGA, patients’ global assessment of disease activity; PBO, placebo; PsA, psoriatic arthritis; PtPain, patients’ assessment of pain; QD, once daily; SJC66, swollen joint count in 66 joints; TJC68, tender joint count in 68 joints; UPA, upadacitinib.

Figure 3

Change from baseline in PROs by (A) MDA, (B) DAPSA LDA, (C) PASDAS LDA, and (D) RAPID3 LDA responder status in SELECT‐PsA 1 and SELECT‐PsA 2 at week 104 (AO data). MDA response was defined as achievement of ≥5 of the 7 MDA components. DAPSA LDA was defined as ≤14. PASDAS LDA was defined as ≤3.2. RAPID3 LDA was defined as ≤6. Results are based on an analysis of covariance model with categorical effects for responder status at week 104, treatment, and current disease‐modifying antirheumatic drug use. Baseline measure is included as a covariate. AO, as observed; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; CI, confidence interval; DAPSA, Disease Activity in Psoriatic Arthritis; EQ‐5D‐5L, 5‐Level EuroQol 5‐Dimension index; FACIT‐F, Functional Assessment of Chronic Illness Therapy‐Fatigue; HAQ‐DI, Health Assessment Questionnaire‐Disability Index; LDA, low disease activity; LS, least squares; MCS, mental component summary; MDA, minimal disease activity; OWI, overall work impairment; NR, nonresponders; PASDAS, Psoriatic Arthritis Disease Activity Score; PCS, physical component summary; PRO, patient‐reported outcome; PsA, psoriatic arthritis; PtGA, patients’ global assessment of disease activity; PtPain, patients’ assessment of pain; RAPID3, Routine Assessment of Patient Index Data 3; R, responders; SF‐36, 36‐item short‐form quality of life questionnaire; WPAI, Work Productivity and Activity Impairment questionnaire. Nominal P values are provided. *P ≤ 0.05. **P ≤ 0.01. ***P ≤ 0.001. ****P ≤ 0.0001.

Figure 4

Achievement of MCID^a in PROs by (A) MDA, (B) DAPSA LDA, (C) PASDAS LDA, and (D) RAPID3 LDA responder status in SELECT‐PsA 1 and SELECT‐PsA 2 at week 104 (AO data). MDA response was defined as achievement of ≥5 of the seven MDA components. DAPSA LDA was defined as ≤14. PASDAS LDA was defined as ≤3.2. RAPID3 LDA was defined as ≤6. AO, as observed; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; DAPSA, Disease Activity in Psoriatic Arthritis; EQ‐5D‐5L, 5‐Level EuroQol 5‐Dimension index; FACIT‐F, Functional Assessment of Chronic Illness Therapy‐Fatigue; HAQ‐DI, Health Assessment Questionnaire‐Disability Index; LDA, low disease activity; MCID, minimal clinically important difference; MCS, mental component summary; MDA, minimal disease activity; NR, nonresponders; OWI, overall work impairment; PASDAS, Psoriatic Arthritis Disease Activity Score; PCS, physical component summary; PRO, patient‐reported outcome; PsA, psoriatic arthritis; PtGA, patients’ global assessment of disease activity; PtPain, patients’ assessment of pain; R, responders; RAPID3, Routine Assessment of Patient Index Data 3; R, responders; SF‐36, 36‐item short‐form quality of life questionnaire; WPAI, Work Productivity and Activity Impairment questionnaire. ^aHAQ‐DI, ≥0.35‐point decrease; SF‐36 PCS, ≥2.5‐point increase; SF‐36 MCS, ≥2.5‐point increase; EQ‐5D‐5L, ≥0.05‐point increase; FACIT‐F, ≥4‐point increase; PtGA, ≥1‐point decrease; PtPain, ≥1‐point decrease; BASDAI, ≥1.1‐point decrease; morning stiffness, ≥1‐point decrease; WPAI OWI, ≥15% improvement. Nominal P values are provided. *P ≤ 0.05. **P ≤ 0.01. ***P ≤ 0.001. ****P ≤ 0.0001.

Figure 5

Association between achievement of MDA or VLDA and composite disease activity measures for upadacitinib 15 mg QD in (A) SELECT‐PsA 1 and (B) SELECT‐PsA 2, and for the pooled upadacitinib treatment arms in (C) SELECT‐PsA 1 and (D) SELECT‐PsA 2 at week 104 (AO data). Nonresponse was defined as achievement of ≤4 of 7 MDA components; MDA (not VLDA) response was defined as achievement of 5 or 6 of the 7 MDA components; VLDA response was defined as achievement of all 7 MDA components. AO, as observed; DAPSA, Disease Activity in Psoriatic Arthritis; EOW, every other week; MDA, minimal disease activity; NR, nonresponders; PASDAS, Psoriatic Arthritis Disease Activity Score; PsA, psoriatic arthritis; QD, once daily; RAPID3, Routine Assessment of Patient Index Data 3; UPA, upadacitinib; VLDA, very low disease activity. ^aUPA 15 mg QD + placebo to UPA 15 mg QD + adalimumab 40 mg EOW. ^bUPA 15 mg QD + placebo to UPA 15 mg QD. Percentages may not total 100% due to rounding. Nominal P values are provided. *P ≤ 0.0001.