Improvement in Patient-Reported Outcomes in Patients with Psoriatic Arthritis Treated with Upadacitinib Versus Placebo or Adalimumab: Results from SELECT-PsA 1

Abstract

Introduction: The aim of this work is to assess the effect of upadacitinib versus adalimumab and placebo on patient-reported outcomes (PROs) in psoriatic arthritis (PsA) patients with inadequate responses to ≥ 1 non-biologic disease-modifying anti-rheumatic drugs (non-bDMARD-IR) in SELECT PsA-1.

Methods: In this placebo- and active comparator, phase 3 randomized, controlled trial, patients received daily upadacitinib 15 or 30 mg, placebo, or adalimumab 40 mg every other week through 56 weeks. At week 24, placebo-assigned patients were rerandomized to upadacitinib 15 or 30 mg. PROs included Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Short Form 36 Health Survey (SF-36), EQ-5D-5L index score, Bath Ankylosing Spondylitis Disease Activity Index, morning stiffness, Self-Assessment of Psoriasis Symptoms, and Work Productivity and Activity Impairment. Mean changes from baseline in PROs, improvements ≥ minimum clinically important differences (MCID), scores ≥ normative values, and sustained clinically meaningful responses were compared between treatment groups.

Results: At weeks 12 and 24, upadacitinib treatment resulted in improvements from baseline versus placebo across all PROs as well as improvements versus adalimumab in HAQ-DI and SF-36 Physical Component Summary score (nominal p < 0.05). Improvements in PtGA, pain, and HAQ-DI were reported as early as week 2. At week 12, significantly (nominal p < 0.05) more upadacitinib- versus placebo-treated patients reported improvements ≥ MCID across all PROs including seven SF-36 domains. The proportions of upadacitinib-treated patients reporting clinically meaningful improvements at week 12 were similar to or greater than with adalimumab and sustained through week 56. Significantly (nominal p < 0.05) more upadacitinib-treated (both doses) patients reported scores ≥ normative values at week 12 versus placebo, and scores were generally similar to or greater than adalimumab.

Conclusions: Upadacitinib treatment provides rapid, sustained, and clinically meaningful improvements in PROs in non-bDMARD-IR patients with PsA. SELECT-PsA 1 ClinicalTrials.gov number, NCT03104400.

Keywords: Adalimumab; 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

Change from baseline through Week 56 in PtGA, pain, HAQ-DI, and FACIT-F over time (MMRM). a PtGA, b Pain, c HAQ-DI, d FACIT-F. *p < 0.05, †p ≤ 0.01, and ‡p ≤ 0.001 for UPA versus ADA. ADA adalimumab, CI confidence interval, FACIT-F Functional Assessment of Chronic Illness Therapy-Fatigue, HAQ-DI Health Assessment Questionnaire Disability Index, LS least squares, MMRM mixed-effects model repeated measurement, PBO placebo, PtGA Patient Global Assessment of Disease Activity, UPA upadacitinib

Fig. 2

SF-36 domain scores at Week 12 relative to age- and gender-adjusted normative values (MMRM). ADA adalimumab, A/G norms age- and gender-matched normative values, BL baseline, BP bodily pain, GH general health, MH mental health, MMRM mixed-effects 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, US United States, VT vitality

Fig. 3

Proportion of patients reporting improvements ≥ MCID and NNTs in PROs at Week 12 (NRI). a PROs, b SF-36 domains. *p < 0.05, †p ≤ 0.01, and ‡p ≤ 0.001 UPA versus placebo and §p < 0.05 and ‖p ≤ 0.01 for UPA versus ADA. aReported only for patients with investigator-determined psoriatic spondylitis at baseline. bMean of BASDAI questions 5 and 6. NNTs were calculated for UPA versus PBO and for ADA versus PBO. NNT for UPA 30 mg was not calculated for MCS and RE because the proportion of patients reporting improvement was not significantly different for UPA 30 mg versus PBO. 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). ADA adalimumab, 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, 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 (NRI) and age- and gender-matched normative values in SF-36 domains. a PROs, b SF-36 domains. *p < 0.05, †p ≤ 0.01, and ‡p ≤ 0.001 UPA versus PBO and §p < 0.05 and ‖p ≤ 0.01 for UPA versus ADA. The percentages at 12 weeks may or may not include the same patients that achieved that outcome at baseline. ADA adalimumab, 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, MCID minimal clinically important difference, MCS Mental Component Summary, MH mental health, 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