OP0038 THE RISK OF ACUTE CORONARY SYNDROME IN PATIENTS WITH RHEUMATOID ARTHRITIS WHO ATTAINED REMISSION WITH METHOTREXATE OR A TUMOR NECROSIS FACTOR INHIBITOR.

Abstract

BackgroundPatients with rheumatoid arthritis (RA) are at higher risk for cardiovascular disease including acute coronary syndromes (ACS) than the general population. Systemic inflammation may mediate some of this increased risk. Treatment with disease modifying anti-rheumatic drugs (DMARDs) may induce remission and thereby lower any increase in ACS risk related to RA inflammation, but the size of this risk reduction vs. rates in the general population, and whether there are, in addition, DMARD-specific beneficial effects on ACS risk, remain unknown.ObjectivesTo compare the incidence rates of ACS in patients with RA who attain remission while treated with a tumor necrosis factor inhibitor (TNFi) vs. methotrexate (MTX), and to anchor these incidence rates to those in the general population.MethodsWe defined and pooled treatment cohorts of patients with RA from clinical rheumatology registers in Norway and Sweden who started MTX or a TNFi between January 01, 2012 and December 31, 2021. To be eligible, patients had to start MTX or TNFi while not being in remission (swollen joint count (SJC) >1 or c-reactive protein (CRP) >10 mg/dL or erythrocyte sedimentation rate (ESR) >20), and had to attain remission in a time window of 90 to 548 days after treatment start. They were followed up for one year from the first date at which remission was recorded until any ACS (as assessed through register linkages) or a censoring event (first of: death from other cause than ACS, emigration, treatment discontinuation (+90 days), a new DMARD treatment start, first non-remission date, end of the study). Patients had to be free from a history of ACS in the 5 years before start of follow-up. One patient could contribute several treatment episodes. We compared the incidence rates of ACS between the two DMARD cohorts using Cox regression analyses with robust standard errors and different adjustments: 1. Country; 2. Country, age, sex, calendar year; 3. Country, age, sex, calendar year, RA disease duration, use of oral corticosteroids, comorbidities (hyperlipidemia, hypertension, diabetes), smoking. The main disease activity (DA) metric for defining remission was DAS28 (DAS28-ESR ≤2.6 or DAS28-CRP ≤2.4). Other metrics were used in sensitivity analyses, including SJC=0, CRP≤10 mg/dL, and patient global health assessment (PGA) ≤14. For each of the Swedish RA patients, general population controls were matched on age and sex and similarly followed-up for ACS.Results14,488 treatment courses with MTX and 13,056 with TNFi were included (25,283 from Sweden and 1786 from Norway). DAS28 remission in the allowed time-window was achieved in 5867 (40%) for MTX and 4147 (32%) for TNFi. At start of follow-up, and compared to the TNFi cohort, the MTX cohort included more male patients (35% vs. 27%), was older (mean age 64 years vs. 58), had a lower disease duration (1.3 years vs. 7.5), was more often treated with steroids (62% vs. 43%), and had more often recorded comorbidities. 70% of the patients in the TNFi cohort were treated with concomitant MTX. During the one-year follow-up (7570 person-years) 15 ACS events were recorded in the MTX cohort and 12 in the TNFi cohort, corresponding to crude incidence rates of 3.4 (95% confidence interval (CI) 2.0-5.6) and 3.8 (95% CI 2.2-6.7) per 1000 person-years. Comparing these incidence rates, the fully adjusted Cox regression analysis (model 3) provided a HR (95% CI) of 1.19 (0.48-2.93) for TNFi vs. MTX. Using other DA metrics provided similar and statistically non-significant estimates (Figure 1). In the matched general population subjects (Sweden only), we observed 128 events. The comparison of the treated (MTX or TNFi) patients in remission to the general population provided a HR (95% CI) of 1.08 (0.70-1.64), adjusted for age, sex and calendar year.ConclusionPatients with RA who reach remission on MTX have a similar ACS risk as those reaching remission on TNFi. The incidence rates of ACS in patients in remission were comparable to the incidence rate in the general population.Figure 1.Cox regression analyses results.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsBénédicte Delcoigne: None declared, Lotta Ljung: None declared, Sella Aarrestad Provan: None declared, Eirik kristianslund: None declared, Johan Askling Grant/research support from: JA has received grants from Abbvie, Astra-Zeneca, BMS, Eli Lily, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB, these entities have entered into agreements with Karolinska Institutet with JA as principal investigator, mainly in the context of safety monitoring of biologics via ARTIS/Swedish Biologics Register.