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

Abstract

ObjectivesTo 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).MethodsA 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.ResultsThe 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).ConclusionsThe 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.

Absence of Association Between Abatacept Exposure and Initial Infection in Patients With Juvenile Idiopathic Arthritis

“…32 Due to a potential immunosuppressive effect, MTX and GCs may lead to a possible increase in infection risk, particularly in a susceptible population 33,34 ; as such, it is important to investigate their use concomitantly with bDMARDs. A systematic literature review and metaanalysis of randomized controlled trials demonstrated that combination therapy with bDMARDs and MTX did not increase the risk of serious infections vs bDMARD monotherapy, 35 in line with the results observed in this analysis (Supplementary Figures 5 and 6, available with the online version of this article). In addition, a systematic literature review of 88 studies showed that long-term (≥ 2 yrs) use of MTX monotherapy was not a risk factor for serious infections, including HZ.…”

Tubercular subretinal abscess in a pediatric intermediate uveitis patient on methotrexate

“…MTX has been found to be safe and efficacious in pediatric uveitis,[ 6 ] but interestingly few authors have noted that as compared with non-JIA children, JIA children on MTX without TNF inhibitors had a significantly increased tuberculosis infection rate. [ 7 8 ] Our patient had no other signs of systemic immunosuppression or of systemic TB. In our case, the SR abscess responded well to ATT and completely resolved with no recurrences till the follow-up period.…”

The Key Comorbidities in Patients with Rheumatoid Arthritis: A Narrative Review

“…csDMARDs and the Risk of Infection in Patients with RA Evidence suggests that csDMARDs, such as methotrexate, confer no increased risk for SI or SI-associated mortality in patients with RA [107]. Indeed, the addition of methotrexate to a bDMARD regimen did not increase the risk of SI compared with bDMARD monotherapy in a meta-analysis of patients with RA [119]. These conclusions, however, differ from those from a Japanese cohort study, which identified the use of methotrexate as a risk factor for Pneumocystis pneumonia, although methotrexate use was negatively associated with the incidence of all infections [93].…”