Patient-Reported Outcomes in Psoriatic Arthritis Patients with an Inadequate Response to Biologic Disease-Modifying Antirheumatic Drugs: SELECT-PsA 2

Abstract

Introduction: Psoriatic arthritis (PsA) has a major impact on health-related quality of life (HRQOL) and other patient-reported outcomes (PROs), important components in the assessment of therapeutic efficacy. We evaluated the impact of upadacitinib on PROs in PsA patients with inadequate responses or intolerance to biologic disease-modifying anti-rheumatic drugs (bDMARD-IR).

Methods: Patients enrolled in the phase 3 SELECT-PsA 2 randomized controlled trial (RCT) received 56 weeks of oral upadacitinib 15 mg QD, upadacitinib 30 mg QD, or placebo switched to either dose of upadacitinib at week 24. PROs included patient global assessment of disease activity (PtGA), pain, physical function (HAQ-DI), health-related quality of life (SF-36 physical (PCS) and mental (MCS) component summary and domain scores), fatigue (FACIT-F), psoriasis symptom severity (SAPS), and work productivity (WPAI). Mean changes from baseline in PROs, improvements ≥ minimum clinically important differences (MCID) and scores ≥ normative values, and maintenance of improvements were assessed.

Results: At weeks 12 and 24, patients treated with either upadacitinib dose reported statistically and nominally significant improvements from baseline across all PROs versus placebo (p ≤ 0.05), except the WPAI absenteeism domain, which were maintained or further improved to week 56. A significantly greater proportion of patients receiving either upadacitinib dose reported improvements ≥ MCID and scores ≥ normative values versus placebo (nominal p ≤ 0.01) in most PROs at weeks 12 and 24, with clinically meaningful improvements continuing to week 56. Improvements ≥ MCID were reported as early as week 2 in PtGA, pain, and HAQ-DI.

Conclusions: Upadacitinib provides rapid, clinically meaningful, and sustained improvements in PROs reported by bDMARD-IR PsA patients. SELECT-PsA 2 ClinicalTrials.gov number, NCT03104374.

Keywords: Activity; Biologic disease-modifying anti-rheumatic drugs; Pain; Patient-reported outcomes; Physical function; Psoriatic arthritis; Quality of life; Upadacitinib; Work productivity.

© 2021. The Author(s).

Figures

Fig. 1

Mean changes from baseline in PtGA, pain, HAQ-DI, and FACIT-F through 56 weeks (MMRM). a PtGA. b Pain. c HAQ-DI. d FACIT-F. CI confidence interval, FACIT-F Functional Assessment of Chronic Illness Therapy-Fatigue, HAQ-DI Health Assessment Questionnaire-Disability Index, LS least squares, MMRM Mixed-Effect Model Repeated Measurement, PBO placebo, PtGA Patient Global Assessment of Disease Activity, UPA upadacitinib

Fig. 2

Week 12 SF-36 domain scores in comparison to age- and gender-matched normative values (MMRM). p values nominal. A/G age-gender adjusted, BL baseline, BP bodily pain, DMARD disease-modifying anti-rheumatic drug, GH general health MH mental health, MMRM Mixed-Effect Model Repeated Measurement, PBO placebo, PF physical functioning, RE role-emotional, RP role-physical, SF social functioning, SF-36 36-Item Short Form Health Survey, UPA upadacitinib, VT vitality

Fig. 3

Proportion of patients reporting improvements ≥ MCID and NNTs in PROs at week 12 (NRI). a PROs excluding SF-36. b SF-36 PCS, MCS, and domains. *p ≤ 0.01 and †p ≤ 0.001 versus placebo. p values nominal. aReported only for patients with investigator-determined psoriatic spondylitis at baseline. bMean of BASDAI questions 5 and 6. NNT not calculated for non-significant results for upadacitinib versus placebo. MCID definitions: ≥ 1-point decrease (PtGA, pain, and morning stiffness), ≥ 0.35-unit decrease (HAQ-DI), ≥ 4-point increase (FACIT-F), ≥ 0.05-unit increase (EQ-5D-5L), ≥ 1.1-point decrease (BASDAI), ≥ 2.5-point increase (SF-36 PCS and MCS), and ≥ 5-point increase (SF-36 domains). BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BP bodily pain, EQ-5D-5L EuroQoL 5-Dimension 5-Level index score, FACIT-F Functional Assessment of Chronic Illness Therapy-Fatigue, GH general health, HAQ-DI Health Assessment Questionnaire-Disability Index, MCID minimal clinically important difference, MCS mental component summary, MH mental health, NA not available, NNT number needed to treat, NRI non-responder imputation, PBO placebo, PCS physical component summary, PF physical functioning, PRO patient-reported outcome, PtGA Patient Global Assessment of Disease Activity, RE role-emotional, RP role-physical, SF social functioning, SF-36 36-Item Short Form Health Survey, UPA upadacitinib, VT vitality

Fig. 4

Proportion of patients reporting PRO scores ≥ normative values at baseline and week 12 and age- and gender-matched normative values in SF-36 domains (NRI). a PROs excluding SF-36 domains. b SF-36 domains. *p < 0.05, †p ≤ 0.01, and ‡p ≤ 0.001 versus placebo. p values nominal. The percentage at 12 weeks might or might not include the same patients that achieved that outcome at baseline. BL baseline, BP bodily pain, EQ-5D-5L EuroQoL 5-Dimension 5-Level index score, FACIT-F Functional Assessment of Chronic Illness Therapy-Fatigue, GH general health, HAQ-DI Health Assessment Questionnaire-Disability Index, MCS mental component summary, MH mental health, NRI non-responder imputation, PBO placebo, PCS physical component summary, PF physical functioning, PtGA Patient Global Assessment of Disease Activity, PRO patient-reported outcome, RE role-emotional, RP role-physical, SF social functioning, SF-36 36-Item Short Form Health Survey, UPA upadacitinib, VT vitality