Pos0061 Interception of the Development of Rheumatoid Arthritis by a 1-Year Course of Methotrexate in Acpa-Negative Arthralgia Patients at Increased Risk for Rheumatoid Arthritis: 4 Year Results of the Treat Earlier Trial

Background: Prevention of rheumatoid arthritis (RA) may go unnoticed in prevention trials that included many low-risk patients due to 'dilution' of a treatment-effect. The TREAT-EARLIER trial in clinically suspect arthralgia (CSA)-patients reported no treatment efficacy for intercepting ACPA-negative RA during 2-years follow-up. However, a large part of ACPA-negative CSA-patients are at low risk of developing RA. Objectives: We hypothesized that prevention of ACPA-negative RA can only be detected after stratifying for risk. Therefore, we studied the efficacy of a 1-year course of methotrexate on reducing RA development in ACPA-negative CSA-patients with increased risk of RA, using TREAT-EARLIER trial data, while taking advantage of 4-years follow-up. Methods: The TREAT-EARLIER trial included 182 ACPA-negative and 54 ACPA-positive CSA-patients with subclinical joint inflammation. Using a previously published prediction model, CSA-patients were grouped in low risk (<25% predicted risk for RA development in 2-years), increased risk (25-70% predicted risk) and high risk (≥70% predicted risk).[1] Development of RA was studied during 4-years follow-up; treatment efficacy was determined per risk group. The severity of MRI-detected joint-inflammation, grip strength and physical functioning was studied in ACPA-negative patients per risk group. Results: Of ACPA-negative CSA-patients, 36% had increased and 64% had low risk. After 4-years in the ACPA-negative increased risk group, 29.0% of the placebo-arm developed RA compared to 8.6% of the treatment-arm (HR 0.27; 95%CI 0.07-0.99) (Figure 1A). In ACPA-negative low risk patients, there was no difference in RA development (9.5% vs 7.5%, HR 0.79; 95%CI 0.22-2.80) (Figure 1B). All ACPA-positive participants were at increased or high risk; despite initial delay of developing ACPA-positive RA, after 4-years there was no difference between placebo- and treatment-arm (52.2% vs 58.1%, HR 0.93; 95%CI 0.45-1.93). In ACPA-negative CSA-patients with increased risk, MRI-detected joint-inflammation, grip strength and physical functioning were persistently improved in the treatment-arm of patients with increased risk, but not in ACPA-negative CSA-patients with low risk. Conclusion: This is the first evidence to suggest that the development of ACPA-negative RA can be intercepted by a 1-year course of methotrexate in patients with CSA. REFERENCES: [1] Matthijssen, X.M.E., et al. Ann Rheum Dis, 2020. Legend figure 1. Kaplan-Meier curves for time to development of RA with 4-years follow-up duration. P-values are calculated by log-rank test. Acknowledgements: NIL. Disclosure of Interests: None declared.