Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT

Abstract

Background: To evaluate the effect of upadacitinib on patient-reported outcomes (PROs) in patients with RA who had an inadequate response to csDMARDs.

Methods: Patients in SELECT-NEXT, a randomised controlled trial, were on a background of csDMARDs and received upadacitinib 15 mg and 30 mg or placebo daily for 12 weeks. 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), duration and severity of morning (AM) joint stiffness, Short Form 36 Health Survey (SF-36), and Work Instability Scale for RA (RA-WIS). Least squares mean (LSM) changes were based on mixed-effect repeated measure models. Percentages of patients reporting improvements ≥ minimum clinically important differences (MCIDs) and scores ≥ normative values and number needed to treat (NNT) were determined; group comparisons used chi-square tests.

Results: Data from 661 patients were analysed. Compared with placebo, patients receiving upadacitinib reported statistically significant improvements (both doses, P < 0.05) in PtGA, pain, HAQ-DI, FACIT-F, duration and severity of AM stiffness, SF-36 (PCS and 6/8 domains), and RA-WIS at week 12. Significantly, more upadacitinib-treated patients (both doses, P < 0.05) reported improvements ≥ MCID in PtGA, pain, HAQ-DI, FACIT-F, AM stiffness, SF-36 (PCS and 4 or 7/8 domains), and RA-WIS and scores ≥ normative values in HAQ-DI, FACIT-F, and SF-36 (PCS and 4 or 5/8 domains). For most PROs, the incremental NNT with upadacitinib to report clinically meaningful improvement from baseline ranged from 4 to 8 patients.

Conclusions: Upadacitinib 15 mg or 30 mg daily for 12 weeks resulted in significant and clinically meaningful improvements in global disease activity, pain, physical function, fatigue, duration and severity of AM stiffness, HRQOL, and work instability among csDMARD-IR patients with RA.

Trial registration: Clinicaltrials.gov, NCT02675426. Retrospectively registered 5 February 2016.

Keywords: Health-related quality of life; JAK inhibitor; Patient-reported outcomes; Rheumatoid arthritis; Treatment outcomes.

Conflict of interest statement

VS is a consultant for AbbVie, Amgen, AstraZeneca, BMS, Celgene, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer, Regeneron, Sanofi, and UCB, and is involved in the advisory boards for AbbVie, Amgen, AstraZeneca, BMS, Celgene, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer, Regeneron, Sanofi, and UCB. JP is a consultant for AbbVie, Amgen, BMS, Celltrion, GSK, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB. NT, AF, HSC, AP, AG, and MF are employees of AbbVie and may own AbbVie stock or stock options. DG is an employee of Analysis Group, Inc., which received consulting fees from AbbVie for this study. MS is a consultant for AbbVie, BMS, Eli Lilly, JNJ, and UCB, and is a member of the speaker bureau for AbbVie and BMS.

Figures

Fig. 1

Baseline and post-treatment scores at week 12 across all Short Form 36 Health Survey domains. Baseline (BL) and SF-36 domain scores are relative to age- and gender-adjusted norms (A/G norms) for the general US population. a PBO. b UPA 15 mg. c UPA 30 mg. d Combined. In the combined spydergrams, most of the UPA 30-mg results are covered up by the UPA 15-mg results. BL values and SF-36 domain scores were re-scored from 0 to 100. No further transformations were applied for this analysis. BP, Bodily Pain; GH, General Health; MH, Mental Health; PBO, placebo; PF, Physical Functioning; RE, Role-Emotional; RP, Role-Physical; SF, Social Functioning; UPA, upadacitinib; VT, Vitality; Wk, week

Fig. 2

Percentage of patients reporting improvements ≥ MCID at week 12. a Patient’s Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), morning (AM) joint stiffness duration, AM stiffness severity, Work Instability Scale for RA (RA-WIS), and Short Form 36 Health Survey (SF-36). b SF-36 individual domains. Baseline values and SF-36 domains were re-scored from 0 to 100. ***P < 0.001, **P < 0.01, *P < 0.5 for upadacitinib versus placebo. BP, Bodily Pain; GH, General Health; MCID, minimum clinically important difference; MCS, mental component summary; MH, Mental Health; NNT, number needed to treat; PBO, placebo; PCS, physical component summary; PF, Physical Functioning; RE, Role-Emotional; RP, Role-Physical; SF, Social Functioning; UPA, upadacitinib; VAS, visual analogue scale; VT, Vitality

Fig. 3

Patients reporting scores ≥ normative values at baseline and week 12. a Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Instability Scale for RA (RA-WIS), and Short Form 36 Health Survey (SF-36) PCS and MCS. b SF-36 individual domains. Baseline values and SF-36 domains were re-scored from 0 to 100. ***P < 0.001, **P < 0.01, *P < 0.5 for upadacitinib versus placebo. BL, baseline; BP, Bodily Pain; GH, General Health; MCS, mental component summary; MH, Mental Health; PBO, placebo; PCS, physical component summary; PF, Physical Functioning; RE, Role-Emotional; RP, Role-Physical; SF, Social Functioning; UPA, upadacitinib; VT, Vitality; Wk, week