Real-World Effectiveness of Upadacitinib for Treatment of Rheumatoid Arthritis in Canadian Patients: Interim Results from the Prospective Observational CLOSE-UP Study

Abstract

Introduction: Upadacitinib (UPA), a selective, reversible, oral Janus kinase (JAK)-1 inhibitor, was approved in 2019 in Canada for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). This phase 4 prospective study aimed to characterise the effectiveness of UPA in the real-world population of patients with RA.

Methods: Adults with RA who initiated treatment with once daily UPA (15 mg) and enrolled in the Canadian Real-Life post-marketing Observational Study assessing the Effectiveness of UPadacitinib for treating rheumatoid arthritis (CLOSE-UP) and who completed a 6-month assessment as of 28 February 2023 were included. The primary endpoint of the CLOSE-UP study is the proportion of patients achieving a Disease Activity Score-28 Joint Count C-reactive protein (DAS28-CRP) < 2.6 at 6 months. Data was collected at routine visits. Data analysed and summarised descriptively for the overall interim population and for subgroups based on prior therapy included remission or low disease activity, patient-reported outcomes (PROs), and adverse events.

Results: A total of 392 patients were included in the interim analysis. Overall, 63.5% (191/301) of patients achieved a DAS28-CRP score < 2.6 at month 6, with similar rates observed for all subgroups analysed according to prior therapy including those with prior JAK inhibitor exposure (range 57.4-71.0%), and in patients who received UPA monotherapy (71.6% [48/67]). Early (month 3) and sustained improvements up to 6 months were observed for all PROs. The safety profile was consistent with previous reports.

Conclusion: Real-world improvements in disease activity and PROs in response to UPA treatment were consistent with clinical trial data across a range of Canadian patients with prior therapy exposure and with UPA monotherapy, with an overall favourable benefit-risk profile.

Trial registration: NCT04574492.

Keywords: Clinical trial; Janus kinase inhibitor; Phase 4; Real-world effectiveness; Rheumatoid arthritis; Upadacitinib.

Fig. 1

Proportion of patients in the overall interim analysis CLOSE-UP population and in subgroups of patients based on exposure to prior therapy achieving (i) DAS28-CRP < 2.6 (solid bars) or DAS28-CRP ≤ 3.2 (shaded bars), or remission (solid bars) or low disease activity (shaded bars) defined according to the (ii) CDAI, (iii) SDAI, and (iv) ACR-EULAR Boolean 2.0 criteria. Abbreviations: ACR-EULAR, American College of Rheumatology-European League Against Rheumatism; CDAI, Clinical Disease Activity Index; DAS28-CRP, Disease Activity Score-28 Joint Count C-reactive protein; SDAI, Simplified Disease Activity Index; tsDMARD, targeted synthetic disease-modifying antirheumatic drugs

Fig. 2

Proportion of patients in the subgroups of patients treated with UPA monotherapy and a combination of UPA and csDMARDs achieving (i) DAS28-CRP < 2.6 (solid bars) or DAS28-CRP ≤ 3.2 (shaded bars), remission (solid bars) or low disease activity (shaded bars) defined according to the (ii) CDAI, (iii) SDAI, (iv) ACR-EULAR Boolean 2.0 criteria, or (v) a 50% reduction in pain score, or minimal clinically important difference in FACIT-F or HAQ-DI scores from baseline. Abbreviations: ACR-EULAR, American College of Rheumatology-European League Against Rheumatism; CDAI, Clinical Disease Activity Index; csDMARD, conventional synthetic disease-modifying antirheumatic drugs; DAS28-CRP, Disease Activity Score-28 Joint Count C-reactive protein; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire-Disability Index; SDAI, Simplified Disease Activity Index; UPA, upadacitinib