Patient-reported outcomes of upadacitinib versus abatacept in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying antirheumatic drugs: 12- and 24-week results of a phase 3 trial

Abstract

Background: In previous clinical trials, patients with active rheumatoid arthritis (RA) treated with upadacitinib (UPA) have improved patient-reported outcomes (PROs). This post hoc analysis of SELECT-CHOICE, a phase 3 clinical trial, evaluated the impact of UPA vs abatacept (ABA) with background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on PROs in patients with RA with inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR).

Methods: Patients in SELECT-CHOICE received UPA (oral 15 mg/day) or ABA (intravenous). PROs evaluated included Patient Global Assessment of Disease Activity (PtGA) by visual analog scale (VAS), patient's assessment of pain by VAS, Health Assessment Questionnaire Disability Index (HAQ-DI), morning stiffness duration and severity, 36-Item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Impairment (WPAI), and EQ-5D 5-Level (EQ-5D-5L) index score. Least squares mean (LSM) changes from baseline to weeks 12 and 24 were based on an analysis of covariance model. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCID) were compared using chi-square tests.

Results: Data from 612 patients were analyzed (UPA, n=303; ABA, n=309). Mean age was 56 years and mean disease duration was 12 years. One-third received ≥2 prior bDMARDs and 72% received concomitant methotrexate at baseline. At week 12, UPA- vs ABA-treated patients had significantly greater improvements in PtGA, pain, HAQ-DI, morning stiffness severity, EQ-5D-5L, 2/4 WPAI domains, and 3/8 SF-36 domains and Physical Component Summary (PCS) scores (P<0.05); significant differences persisted at week 24 for HAQ-DI, morning stiffness severity, SF-36 PCS and bodily pain domain, and WPAI activity impairment domain. At week 12, significantly more UPA- vs ABA-treated patients reported improvements ≥MCID in HAQ-DI (74% vs 64%) and SF-36 PCS (79% vs 66%) and 4/8 domain scores (P<0.05).

Conclusions: At week 12, UPA vs ABA treatment elicited greater improvements in key domains of physical functioning, pain, and general health and earlier improvements in HAQ-DI. Overall, more UPA- vs ABA-treated patients achieved ≥MCID in most PROs at all timepoints; however, not all differences were statistically significant. These data, however, highlight the faster response to UPA treatment.

Trial registration: NCT03086343 , March 22, 2017.

Keywords: JAK inhibitors; Patient-reported outcomes; Rheumatoid arthritis; Targeted synthetic DMARDs; Upadacitinib.

Conflict of interest statement

MB is a consultant/speaker for AbbVie, Amgen, BMS, Genentech/Roche, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi/Regeneron; and shareholder of Johnson & Johnson (parent company of Janssen).

GCW has received speaker and consulting fees from AbbVie and BMS.

NM, JLS, and JP are employees and stockholders of AbbVie.

NT is a former employee of AbbVie and may hold stock.

DG and YS are employees of Analysis Group, Inc., which received consulting fees from AbbVie for this study.

© 2022. The Author(s).

Figures

Fig. 1

Proportion of patients reporting improvements ≥ MCIDa in PROs at weeks 12 (A) and 24 (B). aMCID was defined as reduction of ≥10 mm for PtGA and pain, ≥1 for severity of AM stiffness, reduction of ≥0.22 units for HAQ-DI, increase of ≥4 points for FACIT-F, proxied at one-half standard deviation for duration of AM stiffness, increase of ≥0.05 points for EQ-5D-5L, reduction of 7% in score for WPAI, and increase of ≥2.5 points for SF-36 PCS and MCS. bABA IV at day 1 and weeks 2, 4, 8, 12, 16, and 20 (<60 kg: 500 mg; 60–100 kg: 750 mg; >100 kg: 1,000 mg). cNNTs are for UPA vs ABA. ABA abatacept, AM morning, EQ-5D-5L(index score), EQ-5D 5-Level, FACIT-F Functional Assessment of Chronic Illness Therapy-Fatigue, HAQ-DI Health Assessment Questionnaire Disability Index, IV intravenous, MCID minimal clinically important difference, MCS Mental Component Summary. NNT number needed to treat, PCS Physical Component Summary, PRO patient-reported outcome, PtGA Patient Global Assessment of Disease Activity, SF-36 36-Item Short Form Health Survey, UPA upadacitinib, VAS visual analog scale, WPAI Work Productivity and Activity Impairment. *P<0.05 for UPA vs ABA. P values represent statistical significance between treatment groups

Fig. 2

Proportion of patients reporting improvements ≥ MCIDa in SF-36 at weeks 12 (A) and 24 (B). aMCID was defined as increase ≥5.0 for all SF-36 domains. bABA IV at day 1 and weeks 2, 4, 8, 12, 16, and 20 (<60 kg: 500 mg; 60–100 kg: 750 mg; >100 kg: 1000 mg). cNNTs are for UPA vs ABA. ABA abatacept, BP bodily pain, GH general health, IV intravenous, MCID minimal clinically important difference, MH mental health, PF physical functioning, RE role emotional, RP role physical, SF social functioning, SF-36 36-Item Short Form Health Survey, UPA upadacitinib, VT vitality. *P<0.05 for UPA vs ABA. P values represent statistical significance between treatment groups