Pos0596 Speed and Stability of Disease Control in Early Rheumatoid Arthritis After Remission-Induction Treatment With Methotrexate and Bridging Glucocorticoids: Secondary Outcomes of the Carera2020 Trial

Background: In the CareRA2020 trial, early access to 24 weeks etanercept (Bio-induction COBRA-Slim, CS) was not superior in terms of disease control over 2 years compared to addition of leflunomide (Standard-CS) in patients with early Rheumatoid Arthritis (RA) insufficiently responding to an initial remission-induction regimen of methotrexate (MTX) and step-down glucocorticoids. However, b/tsDMARD and oral glucocorticoid use at Week (W) 104 was higher in Standard-CS compared to Bio-induction-CS. Objectives: To determine the speed and long-term stability of disease control in patients with early RA after initial COBRA-Slim remission-induction followed by a treat-to-target (T2T) approach. Methods: DMARD-naïve patients with early RA (diagnosis ≤1y) were included in the 2-year, open-label, multicentre randomised controlled CareRA2020 trial. All patients started a remission-induction regimen with MTX and a step-down prednisone scheme starting from 30 mg/d. In case of an early insufficient response between W8 – W32, defined as DAS28-CRP >3.2 from W8 onwards, or DAS28-CRP ≥2.6 at W32, patients were 1:1 randomised to a "second-hit" remission-induction regimen: addition of leflunomide (Standard-CS) or etanercept for 24 weeks (Bio-induction-CS). Further following a T2T-approach, a DAS28-CRP threshold of ≤3.2 was aimed for. To investigate the speed of response to the second-hit remission-induction regimen in early insufficient responders, the time until first achievement of DAS28-CRP <2.6 after randomisation was determined. The proportion of patients with sustained disease control defined as DAS28-CRP <2.6 for at least 24 weeks, as well as sustained remission based on SDAI (≤3.3) was determined for the early responder as well as both early insufficient responder groups. Data were multiple imputed (m=100), and were analysed descriptively. Results: In CareRA2020, 142 patients were early responders (67% female, mean ± SD age 54.9 ± 13.9y) to the initial remission-induction regimen, 55 early insufficient responders were randomised to Standard-CS (75% female, age 53.4 ± 13.1y), and 55 to Bio-induction-CS (69% female, age 52.5 ± 12.9y). Between BL-W104, 94% [95% CI 88 - 97] early responders achieved sustained DAS28-CRP disease control for at least 24 weeks (sustained SDAI disease control: 64% [55 - 72]). This was 86% [79 - 91] between BL-W64 (SDAI: 50% [41 - 58]), and 76% [68 - 83] between W64-W104 (SDAI: 41% [32 - 50]). Moreover, 38% [30 - 47] of early responders had a DAS28-CRP <2.6 at every study visit between BL-W104 (SDAI ≤3.3 at every study visit: 9% [5 - 15]). After randomisation, Bio-induction-CS achieved DAS28-CRP <2.6 more rapidly compared to Standard-CS (Figure 1). However, a comparable proportion of patients in both randomisation groups maintained DAS28-CRP <2.6 for at least 24 weeks after randomisation until W104 (Standard-CS: 51% [37 - 65], Bio-induction-CS: 45% [32 - 60]) (SDAI: 14% [7 - 26] and 13% [6 - 26], respectively). When considering all visits after randomisation, the proportion of patients maintaining DAS28-CRP <2.6 until the study end was also comparable between the two groups (Standard-CS: 9% [4 - 22], Bio-induction-CS: 8% [3 - 20]) (SDAI: 0% for both randomisation groups). Conclusion: CareRA2020 confirmed that a remission-induction regimen with MTX and bridging prednisone is a highly effective treatment for patients with early RA, as 94% of early responders achieved sustained disease control for at least 24 weeks between BL and W104. In early insufficient responders to the initial regimen, a second-hit remission-induction regimen with 24 weeks of etanercept yielded a more rapid achievement of DAS28-CRP <2.6 compared to addition of leflunomide. However, after randomisation both groups had comparable sustained disease control for at least 24 weeks during the trial. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.