Abstract 1339: Combination TNF Inhibitor-Methotrexate Therapy is Superior to Methotrexate Monotherapy in Reducing the Risk of Acute Myocardial Infarction in Patients with Rheumatoid Arthritis
Authors:
G. Singh, S. Vadhavkar, A. Mithal, G. Triadafilopoulos
Background
Methotrexate (MTX) use has been linked to a decreased risk of cardiovascular and all cause mortality in RA patients compared to non-users. In addition, several reports have suggested that TNF inhibitor use may be associated with a reduced risk of myocardial infarction (MI). Here, Singh et al investigate whether the combination of MTX plus a TNF inhibitor exerts an additive benefit on risk of MI in RA.
Methods
A nested case-control study was performed using the MediCal database, a registry of over 7 million medical assistance patients in California including diagnoses and medication use (prescription and over the counter (OTC)). Cases were RA patients without non-cardiovascular life threatening illness treated with DMARDs between January 1, 1999 to June 30, 2005 who were identified as having their first acute MI, defined as requiring three or more days in the hospital after MI diagnosis or death from MI. Four eligible gender, age, and time matched RA controls without MI were selected for each case. Incident MI was compared according to prior exposure to DMARDs, defined as current, recent, or remote. Exposure groups were divided into categories: MTX monotherapy (reference group), TNF inhibitor monotherapy, TNF inhibitor + MTX combination therapy, TNF inhibitor + non-MTX combination therapy, non-MTX monotherapy, MTX + non-MTX combination therapy.
Results
There were 19,223 RA patients enrolled totaling 74,006 patient-years of follow-up. Among these, 441 cases of MI were identified and exposure status was compared to 1760 matched controls. Eight percent of MI cases were fatal. There was an 80% reduction in risk of MI in patients treated with TNF inhibitor + MTX combination therapy compared to those treated with methotrexate alone (adjusted RR 0.20 (95%CI 0.05 – 0.88)). Other DMARD combination and montherapies did not significantly differ in adjusted risk of MI compared to MTX monotherapy. Incidentally, the adjusted risk of MI was 37% greater in corticosteroid users compared to non-users (RR 1.37 (95% CI 1.07 – 1.75)).
Conclusions
Among RA therapies, the combination of TNF inhibitor + MTX was associated with a significant reduction in acute MI compared to MTX monotherapy
Editorial Comment
RA therapy with the combination of TNF inhibitor + methotrexate has been shown to have potent anti-inflammatory properties, possibly explaining some of the reduction in acute MI seen in this investigation. However, other factors associated with reduced MI, such as the ability to reduce prednisone and NSAID dosing, improved physical function and fitness, and others, may be as responsible for the observed reduction as any direct anti-inflammatory effect at the level of the coronary artery. This study benefits from its large sample size and collection of data not typically found in administrative databases (such as OTC drug use). However, there are issues of selection and generalizability that arise due to the design. Generalizability may be an issue as the population in question is exclusively derived from a medical assistance population. Selection bias may arise from the fact that certain DMARD combinations are used in patients because of factors that may relate to the outcome. For example, TNF inhibitors are generally prescribed to patients with worse disease activity but less comorbidity. In general, these selection issues are difficult, if not impossible, to adjust for in these types of analyses. Importantly, a recent analysis has questioned whether these selection issues may be the sole explanation for the reduced risk of MI associated with TNF inhibitor use observed in several observational cohorts.
