Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs

Abstract

Background: Patient-reported outcomes (PROs) are important when evaluating treatment benefits in rheumatoid arthritis (RA). We compared upadacitinib, an oral, selective JAK-1 inhibitor, with placebo to assess clinically meaningful improvements in PROs in patients with RA who have had inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARD-IR).

Methods: PRO responses between upadacitinib 15 mg or 30 mg and placebo were evaluated at week 12 from the SELECT-BEYOND trial. Improvement was determined by measuring Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36), duration and severity of morning (AM) stiffness, and Insomnia Severity Index (ISI). Least squares mean changes and percentage of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores greater than or equal to normative values were determined. The number needed to treat (NNT) to achieve clinically meaningful improvements was calculated.

Results: In 498 patients, both upadacitinib doses resulted in statistically significant changes from baseline versus placebo in PtGA, pain, HAQ-DI, SF-36 Physical Component Summary (PCS), 7 of 8 SF-36 domains (15 mg), 6 of 8 SF-36 domains (30 mg), and AM stiffness duration and severity. Compared with placebo, more upadacitinib-treated patients reported improvements ≥ MCID in PtGA, pain, HAQ-DI, SF-36 PCS, 7 of 8 SF-36 domains (15 mg), 5 of 8 SF-36 domains (30 mg), AM stiffness duration and severity, and ISI (30 mg) and scores ≥ normative values in HAQ-DI and SF-36 domains. Across most PROs, NNTs to achieve MCID with upadacitinib ranged from 4 to 7 patients.

Conclusions: In bDMARD-IR RA patients, upadacitinib (15 mg or 30 mg) improved multiple aspects of quality of life, and more patients reached clinically meaningful improvements approaching normative values compared with placebo.

Trial registration: The trial is registered with ClinicalTrials.gov (NCT02706847), registered 6 March 2016.

Keywords: Fatigue; HAQ; JAK inhibitor; MCID; Pain; Patient-reported outcome measures; Quality of life; Rheumatoid arthritis; SF-36; Treatment outcomes; Upadacitinib.

Conflict of interest statement

VS is a consultant for AbbVie, Amgen, AstraZeneca, BMS, Celgene, Genentech, GSK, Janssen, Eli Lilly, Novartis, Pfizer, Regeneron, Sanofi, and UCB, and is involved in advisory boards for AbbVie, Amgen, AstraZeneca, BMS, Celgene, Genentech, GSK, Janssen, Eli Lilly, Novartis, Pfizer, Regeneron, Sanofi, and UCB.

MS is a consultant for AbbVie, BMS, Eli Lilly, JNJ, and UCB, and is a member of the speaker bureau for AbbVie and BMS.

JP is a consultant for AbbVie, Amgen, BMS, Celltrion, GSK, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, Sandoz, and UCB.

NT, AF, SM, AP, and MF are employees of AbbVie and may own AbbVie stock or stock options.

AG is a former employee of AbbVie and may own AbbVie stock or stock options.

YS is an employee of Analysis Group Inc., which received consulting fees from AbbVie for this study.

Figures

Fig. 1

BL and week 12 scores across SF-36 domains relative to age- and gender-adjusted (A/G) norms for the general US population. a Placebo. b UPA 15 mg. c UPA 30 mg. d Combined. All scores were based on a scale of 0 to 100, where 0 is the worst and 100 is the best. No further transformations were applied. *P < 0.05 for UPA 15 mg vs PBO. **P < 0.05 for UPA 30 mg vs PBO. BL, baseline; BP, bodily pain; GH, general health; MH, mental health; PBO, placebo; PF, physical functioning; RE, role-emotional; RP, role-physical; SF, social functioning; SF-36, Short Form-36 Health Survey; UPA, upadacitinib; VT, vitality; Wk, week

Fig. 2

Patients reporting improvements ≥ MCID at week 12 across PROs. a Results from multiple patient health-related quality of life assessments. b Results from the SF-36 subdomains. SF-36 domains were rescored from 0 to 100, where 0 is the worst and 100 is the best. No further transformations were applied. *P < 0.05 for UPA vs PBO. AM, morning; BP, bodily pain; EQ-5D-5L, Euro Qol 5-Dimension 5-Level Questionnaire; GH, general health; HAQ-DI, Health Assessment Questionnaire Disability Index; ISI, Insomnia Severity Index; 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; PRO, patient-reported outcome; PtGA, Patient Global Assessment of Disease Activity; RE, role-emotional; RP, role-physical; SF, social functioning; SF-36, Short Form-36 Health Survey; UPA, upadacitinib; VAS, visual analog scale; VT, vitality

Fig. 3

Patients reporting scores ≥ normative values. a Select PROs at baseline and week 12. b Short Form 36 (SF-36) domains. SF-36 domains were rescored from 0 to 100, where 0 is the worst and 100 is the best. No further transformations were applied. *P < 0.05 for UPA vs PBO. BL, baseline; BP, bodily pain; EQ-5D-5L, Euro Qol 5-Dimension 5-Level Questionnaire; GH, general health; HAQ-DI, Health Assessment Questionnaire Disability Index; ISI, Insomnia Severity Index; MCS, Mental Component Summary; MH, mental health; PBO, placebo; PCS, Physical Component Summary; PF, physical functioning; PRO, patient-reported outcome; RE, role-emotional; RP, role-physical; SF, social functioning; SF-36, Short Form-36 Health Survey; UPA, upadacitinib; VT, vitality; Wk, week