Upadacitinib as monotherapy in patients with rheumatoid arthritis and prior inadequate response to methotrexate: results at 260 weeks from the SELECT-MONOTHERAPY randomised study.

INTRODUCTION

The phase III SELECT-MONOTHERAPY trial (NCT02706951) demonstrated the safety and efficacy of upadacitinib (UPA) monotherapy through 84 weeks in patients with rheumatoid arthritis who responded inadequately to methotrexate. Here we report week 260 results.

METHODS

Patients were randomised to continue methotrexate or UPA 15 mg (UPA15) or 30 mg (UPA30) monotherapy for 14 weeks. From week 14, patients continuing methotrexate switched to UPA15 or UPA30 per prespecified assignment; patients randomised to UPA continued treatment. Following a protocol amendment, all cohorts switched to open-label UPA15. Safety was summarised using exposure-adjusted event and incidence rates. Efficacy was reported as observed and using non-responder imputation (NRI).

RESULTS

Of 648 randomised patients, 598 entered the long-term extension. Of these, 249 (41.6%) discontinued study drug by week 260 primarily due to adverse events (14.5%), consent withdrawal (9.9%), lost to follow-up (3.3%), lack of efficacy (2.2%), COVID-19 (0.7%) or other reasons (11.0%). Rates of herpes zoster, non-melanoma skin cancer, hepatic disorder, neutropenia, lymphopenia and creatine kinase elevation were higher with UPA30 versus UPA15. Long-term UPA safety data were consistent with the established UPA safety profile. Based on NRI, >39% of patients treated continuously with UPA achieved low disease activity per Clinical Disease Activity Index ≤10 (UPA15, n=93/217; UPA30, n=91/215) and 28-joint Disease Activity Score using C reactive protein ≤3.2 (UPA15, n=90/217; UPA30, n=94/215) at week 260. Efficacy was similar among patients switching from methotrexate to UPA.

CONCLUSION

No new safety risks were identified with long-term UPA treatment. UPA monotherapy was efficacious in treating rheumatoid arthritis through week 260.

TRIAL REGISTRATION NUMBER: NCT02706951.