No impact of concomitant methotrexate use on serious adverse event and serious infection risk in patients with rheumatoid arthritis treated with bDMARDs: a systematic literature review and meta-analysis

OBJECTIVES: To compare the risk of serious adverse events, serious infections and death caused by methotrexate and biological disease-modifying antirheumatic drug (bDMARD) combination therapy versus a bDMARD prescribed as monotherapy in rheumatoid arthritis (RA). METHODS: A systematic literature review was conducted until February 2016 in PubMed, Embase and Cochrane Library databases by selecting randomised controlled trials comparing methotrexate and bDMARD combination therapy to bDMARD monotherapy in RA. The meta-analysis compared the occurrence of (1) serious adverse events, (2) serious infections and (3) death among these groups by the Mantel-Haenszel method. RESULTS: The literature review selected 16 controlled trials comparing methotrexate and bDMARD combination therapy to bDMARD monotherapy. After meta-analysis comparing patients under monotherapy to those under combination therapy: (1) the risk of occurrence of serious adverse events was comparable in 12 trials: RR (95% CI) 0.92 (0.78 to 1.08). (2) No significant difference was observed in the risk of occurrence of serious infections in 13 trials: RR (95% CI) 1.15 (0.84 to 1.58). We noted a trend, although insignificant, towards a high risk of the occurrence of tuberculosis in 10 studies: RR (95% CI) 1.78 (0.63 to 4.99). (3) The risk of death was comparable in 12 trials: RR (95% CI) 0.73 (0.40 to 1.35). CONCLUSIONS: The results showed no significant difference between the two groups, confirming that the use of methotrexate and bDMARD combination therapy in RA does not cause an increased risk of serious adverse events or serious infections or death compared with bDMARD monotherapy.