Risk of Serious Infection Among Initiators of Tumor Necrosis Factor Inhibitors Plus Methotrexate Versus Triple Therapy for Rheumatoid Arthritis: A Cohort Study.

OBJECTIVE

To compare the risk of serious infections between the use of tumor necrosis factor inhibitors (TNFi) plus methotrexate (MTX) versus triple therapy among rheumatoid arthritis (RA) patients in a real-world setting.

METHODS

Using claims data from Truven MarketScan (2003-2014), we conducted a cohort study to compare RA patients receiving MTX who added a TNFi (TNFi plus MTX group) versus MTX plus hydroxychloroquine and sulfasalazine (triple therapy group). The primary outcome was any serious infection (i.e., a composite end point of hospitalized bacterial and opportunistic infections or herpes zoster). Secondary outcomes were individual components of the composite end point. To adjust for baseline confounding, we used propensity score (PS)-based fine stratification and weighting. A weighted Cox proportional hazards model estimated the hazard ratio (HR) and 95% confidence interval (95% CI) of the outcomes.

RESULTS

After PS stratification (PSS) and weighting, we included a total of 45,208 TNFi plus MTX initiators and 1,387 triple therapy initiators. Mean age was 53 years and 70% were female. The incidence rate of any serious infection per 100 person-years was 2.46 in the TNFi plus MTX group and 2.03 in the triple therapy group. The PSS-weighted HR for any serious infection comparing TNFi plus MTX versus triple therapy was 1.23 (95% CI 0.87-1.74). For the secondary outcomes, the PSS-weighted HR was 1.41 (95% CI 0.85-2.34) for bacterial infection and 0.80 (95% CI 0.55-1.18) for herpes zoster.

CONCLUSION

In this real-world cohort of RA patients, we noted no substantially different risk of any serious infection, bacterial infection, or herpes zoster after initiating TNFi plus MTX versus triple therapy, although CIs were wide.