Achieving Remission with Methotrexate or TNFi Linked to Lower CV Risk in Rheumatoid Arthritis


An analysis of patient data from Sweden and Norway detail the impact of achieving remission with methotrexate or TNF inhibitors on risk of acute coronary syndrome in patients with rheumatoid arthritis.

Bénédicte Delcoigne, PhD, MSc | Credit: Karolinska Institute

Bénédicte Delcoigne, PhD, MSc
Credit: Karolinska Institute

An analysis of patient data from a pair of European nations is offering clinicians with insight into the risk of acute coronary syndrome in patients with rheumatoid arthritis based on whether they have attained remission with a methotrexate or a tumor necrosis factor (TNF) inhibitor.

Results of the study, which were presented at the European Congress of Rheumatology (EULAR) 2023 annual meeting, indicate the risk of acute coronary syndrome was similar for those who achieved remission using methotrexate relative to their counterparts achieving remission with a TNF inhibitor, with overall incidence rates of acute coronary syndrome in patients in remission comparable to the incidence rate in the general population.1

“Patients with [rheumatoid arthritis] who reach remission on MTX have a similar ACS risk as those reaching remission on TNF inhibitors,” said Bénédicte Delcoigne, PhD, MSc, a statistician from the Karolinska Institutet in Stockholm, Sweden.2 “The incidence rates of [acute coronary syndrome] in patients in remission were comparable to the incidence rate in the general population.”

As multidisciplinary care has become more of a focal point in the management of patients, interest has grown in managing the increased cardiovascular risk associated with rheumatic disease, including a recent systematic review and meta-analysis, which found use of TNF inhibitors was associated with a favorable effect on surrogate markers for cardiovascular disease risk.3 Citing an interest in exploring differences in risk for acute coronary syndrome based on achievement of remission with either methotrexate or a TNF inhibitor in patients with rheumatoid arthritis, Delcoigne and a team of colleagues from the Karolinska Institute designed the current study as an analysis of data from clinical rheumatology registers in Norway and Sweden.1

For inclusion in the analysis, patients needed to have started therapy with methotrexate or a TNF inhibitor between 2012-2021 while not being in remission. Further inclusion criteria required patients to have achieved remission with 90-548 days of beginning treatment and have no history of acute coronary syndrome for at least 5 years preceding study entry. For the purpose of analysis, patients were followed for 1-year from the first date at which remission was recorded until any acute coronary syndrome event or a censoring event, which included first incidence of mortality from any cause other than acute coronary syndrome, emigration, treatment discontinuation of 90 days or longer, new DMARD treatment start, the first non-remission date, or the end of the study.1

Investigators used Cox regression analyses to compare incidence rates of acute coronary syndrome among the study. Cohorts. Of note, the fully adjusted model accounted for country, age, sex, calendar year,disease duration, use of oral corticosteroids, comorbidities, and smoking status. Overall, investigators identified 14,488 treatment courses with methotrexate and 13,056 with TNF inhibitors during the period of interest. Initial analysis indicated DAS28 remission in the allowed time window was achieved in 40% using methotrexate and 4147 using TNF inhibitors.1

During the 1-year follow-up, investigators identified 15 acute coronary syndrome events among those who achieved remission with methotrexate and 12 acute coronary syndrome events among toe who achieved remission with a TNF inhibitor. Investigators noted this corresponds with crude incidence rates of 3.4 (95% Confidence interval [CI], 2.0-5.6) and 3.8 (95% CI, 2.2-6.7) events per 1000 person-years for the methotrexate and TNF inhibitor groups, respectively.1

When comparing incidence rates, the full-adjusted model suggested risk of acute coronary syndrome was 19% greater among those achieving remission with TNF inhibitors relative to methotrexate (Hazard Ratio [HR], 1.19 [95% CI, 0.48-2.93]). Using other disease activity metrics, investigators observed methotrexate and TNF inhibitors provided similar and statistically non-significant estimates. When compared to the matched general population, patients achieving remission, regardless of therapy used, had an 8% increase in risk of acute coronary syndrome relative to their healthy counterparts after adjustment for age, sex, and calendar year.1


  1. Delcoigne B, Ljung L, Aarestad Provan S, et al. THE RISK OF ACUTE CORONARY SYNDROME IN PATIENTS WITH RHEUMATOID ARTHRITIS WHO ATTAINED REMISSION WITH METHOTREXATE OR A TUMOR NECROSIS FACTOR INHIBITOR. Paper presented at: European Congress of Rheumatology (EULAR) 2023. Milan, Italy. May 31 – June 3, 2023.
  2. EULAR 2023. CARDIOVASCULAR CONSIDERATIONS IN RA. EULAR Press Releases. May 31, 2023. Accessed May 31, 2023.
  3. Iapoce C. TNF inhibitors may reduce CVD risk in patients with rheumatoid arthritis. HCP Live. January 20, 2023. Accessed May 31, 2023.
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