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

Vibeke Strand,Debbie Goldschmidt,Aileen Pangan,Janet Pope,Heidi S Camp,Arijit Ganguli,Michael Schiff,Mahesh Fuldeore,Namita Tundia,Alan Friedman

doi:10.1186/s13075-019-2037-1

Abstract

BackgroundTo evaluate the effect of upadacitinib on patient-reported outcomes (PROs) in patients with RA who had an inadequate response to csDMARDs.MethodsPatients 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.ResultsData 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.ConclusionsUpadacitinib 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 registrationClinicaltrials.gov, NCT02675426. Retrospectively registered 5 February 2016.

Highlights

To evaluate the effect of upadacitinib on patient-reported outcomes (PROs) in patients with Rheumatoid arthritis (RA) who had an inadequate response to Conventional synthetic disease-modifying antirheumatic drug (csDMARD)
We examined the effect of two doses (15 mg or 30 mg daily) of upadacitinib versus placebo on PROs in SELECT-an Randomised controlled trial (RCT) assessing the efficacy and safety of upadacitinib in moderately to severely active csDMARD-Inadequate response (IR) RA patients
The RCT was conducted in accordance with the ethical principles that have their origin in the current Declaration of Helsinki and consistent with International Conference on Harmonisation Good Clinical Practice and Good Epidemiology Practices, along with all applicable local regulatory requirements

Summary

Introduction

To evaluate the effect of upadacitinib on patient-reported outcomes (PROs) in patients with RA who had an inadequate response to csDMARDs. Core patient-reported outcomes (PROs) including global assessment of disease, pain, physical function, fatigue, HRQOL, and work stability provide valuable insights into patients’ perspectives on their health status and impact of disease—improvements in PROs are considered important when evaluating the benefits of treatments [14–18]. Upadacitinib, a selective JAK1 inhibitor, has demonstrated efficacy and a favourable benefit-to-risk profile in active RA among patients with inadequate responses to conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR) in phase 2 and 3 RCTs (NCT02066389; NCT02675426) [24, 25]. To assess the comprehensive benefits of upadacitinib, it is important to understand its impact on patient-centric outcomes To this end, we examined the effect of two doses (15 mg or 30 mg daily) of upadacitinib versus placebo on PROs in SELECT-an RCT assessing the efficacy and safety of upadacitinib in moderately to severely active csDMARD-IR RA patients

Methods

Results

Discussion

Conclusion