Background Monotherapy use of upadacitinib (UPA), a selective JAK1 inhibitor, demonstrated clinically meaningful improvement in the signs and symptoms of rheumatoid arthritis (RA) compared with methotrexate (MTX).¹ To better understand the impact of UPA treatment in RA from the patient’s perspective, we examined the effect of UPA on patient-reported outcomes (PROs).

Objectives To evaluate the effect of UPA monotherapy vs MTX at week 12 on PROs in SELECT-EARLY (NCT02706873), a randomised controlled trial in MTX-naïve patients with moderate to severe RA.

Methods Patients were randomised 1:1:1 to receive once daily UPA (15 mg or 30 mg) or weekly MTX (titrated by Week 8). PROs assessed included Patient Global Assessment of Disease Activity (PtGA) by visual analogue scale (VAS), pain by VAS, physical function by Health Assessment Questionnaire Disability Index (HAQ-DI), fatigue by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), duration and severity of morning (AM) stiffness, HRQoL by Short Form 36 (SF-36), and Work Productivity and Activity Impairment (WPAI) measure. Least square mean (LSM) changes from baseline (BL) to Week 12 were based on analysis of covariance. Percentages of patients reporting changes in PRO scores from BL to Week 12 ≥ minimum clinically important differences (MCIDs) or scores ≥ normative values (age- and gender-matched for SF-36 only) were determined for UPA and MTX groups; comparisons used chi-square tests. For each PRO, the incremental number needed to treat (NNT) to achieve clinically meaningful improvement from BL was calculated.

Results Data from 945 patients (MTX: 314; UPA 15 mg: 317; UPA 30 mg: 314) were analysed. Mean age was 53 years; 76% were female; 49% had RA for <6 months. Statistically significant LSM changes from BL to Week 12 were reported for both doses of UPA vs MTX for all PROs (Table). At Week 2, both UPA doses had significantly higher proportions of patients reporting improvements ≥ MCID vs MTX in HAQ-DI, duration and severity of AM stiffness, pain, and PtGA. Compared with MTX at Week 12, a significantly greater proportion of patients receiving UPA at either dose reported improvements ≥ MCID in all PROs. A significantly greater proportion of patients receiving UPA also reported scores ≥ normative values for all PROs except SF-36 Mental Health (UPA 15 mg) and SF-36 General Health (both UPA doses) domains. For most PROs, NNTs with UPA ranged from 4 to 8 patients at Week 12.

Conclusion Among MTX-naïve patients with active RA, treatment with UPA 15 mg or 30 mg daily for 12 weeks resulted in statistically significant and clinically meaningful improvements in physical function, pain, fatigue, AM stiffness, HRQoL, and work productivity compared with MTX. The NNTs to achieve these improvements were favourable.

Reference [1] van Vollenhoven R, et al. Arthritis Rheumatol. 2018;70(S9):983, abstract 891.

Acknowledgement Financial support for the study was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the abstract. All authors contributed to the development of the publication and maintained control over the final content. Medical writing services were provided by Joann Hettasch of JK Associates Inc., a member of the Fishawack Group of Companies, and funded by AbbVie.

Disclosure of Interests Vibeke Strand Consultant for: AbbVie, Amgen, Bayer, BMS, Boehringer Ingelheim, Celgene, Celltrion, CORRONA, Crescendo, EMD Serono, Genentech/Roche, GSK, Horizon, Inmedix, Janssen, Kezar, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Servier, UCB., Namita Tundia Shareholder of: AbbVie, Employee of: AbbVie, Sebastiao Radominski Consultant for: Abbvie, Celgene, Genentech/Roche, Janssen, Pfizer, UCB, Speakers bureau: Abbvie, Celgene, Genentech/Roche, Janssen, Pfizer, UCB, Alan Friedman Shareholder of: AbbVie, Employee of: AbbVie, Kendall Dunlap Shareholder of: AbbVie, Employee of: AbbVie, Deborah Goldschmidt Employee of: Analysis Group Inc, which received consulting fees from AbbVie for this study., Martin Bergman Shareholder of: Johnson and Johnson (parent company of Janssen), Consultant for: AbbVie, Amgen, BMS, Celgene, Genentech/Roche, Janssen, Merck, Novartis, Pfizer, and Sanofi/Regeneron, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech/Roche, Janssen, Merck, Novartis, Pfizer, and Sanofi/Regeneron