Effectiveness of Upadacitinib in Patients with Rheumatoid Arthritis in Canadian Real-World Practice: Final Results from the Close-Up Post-Marketing Observational Study

Objectives To evaluate the real-world effectiveness and safety of upadacitinib (UPA) among Canadian patients with rheumatoid arthritis (RA) with prior exposure to conventional synthetic (cs)DMARD, biologic (b) DMARD, and targeted-synthetic (ts)DMARD in real-world settings. Methods CLOSE-UP was a prospective, observational post-marketing study conducted at 33 sites in Canada in adults with moderate-to-severe RA who were treated with UPA 15 mg once daily. UPA initiation was decided before study participation. Patients were followed for 24 months after UPA initiation with data collected at routine clinic visits. The primary endpoint was the proportion of patients achieving a Disease Activity Score 28 Joint Count - C-reactive protein (DAS28-CRP) < 2.6 at 6 months. Secondary endpoints included pain score using a visual analog scale, fatigue (FACIT-F), physical function as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and other assessments of disease activity including Clinical Disease Activity Index (CDAI) score. Patients were grouped by prior/most recent exposure to no b/tsDMARDs (bio-naïve), ≤2 bDMARDs but no tsDMARD (bio-experienced), and a maximum of 1 bDMARD followed by a tsDMARD (tsDMARDexperienced). Data are presented as observed and summarized descriptively. Results Analysis included 412 patients, with 47.1% identified as bio-naïve, 41.3% as bio- experienced, and 10.7% as tsDMARD-experienced. At baseline, most patients (84.5%) exhibited a DAS28-CRP > 3.2. After 6 months of UPA treatment initiation, 60.7% of patients achieved a DAS28-CRP < 2.6 (primary endpoint) and 75.6% achieved a DAS28-CRP ≤ 3.2 with a response rate maintained for up to 24 months (Figure 1a). Similar trends were observed using CDAI definitions for clinical remission and low disease activity. The type of prior/most recent DMARD exposure did not impact response. Additionally, the proportion of patients achieving a DAS28-CRP < 2.6 at the 6-month visit were similar between those on UPA monotherapy (62.7%) and those on UPA in combination with a csDMARD (60.1%). Improvements in pain score, fatigue, and physical function were observed throughout the study (Figure 1b). At 6 months, 86.5% of patients persisted in their treatment on UPA and 67.5% persisted up to Month 24. The safety profile of UPA was consistent with that seen in Phase 3 trials with no new safety signals. Conclusion Consistent with clinical trial findings, this real-world Canadian study demonstrated a reduction in disease activity and improvements in patient-reported outcomes, supporting a favorable benefit-risk profile for patients treated with UPA. Notably, response rates were consistent irrespective of prior bDMARDs/tsDMARDs use or concomitant csDMARD.