Patients with rheumatoid arthritis (RA) who initiate a tumor necrosis factor inhibitor (TNFi) plus methotrexate (MTX) do not have significantly different risks for serious infection compared with those who initiate triple therapy, according to results published in Arthritis Care & Research. The researchers did note, however, that their confidence intervals were wide.

The study included participants with RA receiving MTX who added a TNFi (TNFi plus MTX group) and those who added hydroxychloroquine and sulfasalazine (triple-therapy group). The primary outcome was any serious infection, and secondary outcomes were individual components of the composite end point.

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The researchers used propensity score-based fine stratification and weighting to adjust for baseline confounding. They used a weighted Cox proportional hazards model to estimate the hazard ratio and 95% CI of the outcomes. A total of 45,208 participants were included in the TNFi plus MTX group, and 1387 were included in the triple-therapy group.

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The results indicated that the incidence rate of any serious infection per 100 person-years was 2.46 (95% CI, 2.35-2.58) in the TNFi plus MTX group compared with 2.03 (95% CI, 1.44-2.86) in the triple-therapy group. Comparing the 2 groups, the researchers found a propensity score stratification-weighted hazard ratio for any serious infection was 1.23 (95% CI, 0.87-1.74).

For the secondary outcomes, the researchers found a propensity score stratification-weighted hazard ratio of 1.41 (95% CI, 0.85-2.34) for bacterial infection and 0.80 (95% CI, 0.55-1.18) for herpes zoster. The study included several limitations, including the small number of patients receiving triple therapy, possible confounding from RA severity and duration, and a potential for misclassification.

“In this large real-world cohort of RA patients, we found no substantially different risk of any serious infection, bacterial infection or herpes zoster after initiating TNFi plus MTX treatment versus triple therapy,” the researchers wrote.


Kang EH, Jin Y, Tong AY, Desai RJ, Kim SC. Risk of serious infection among initiators of TNF inhibitors plus methotrexate versus triple therapy for rheumatoid arthritis: a cohort study [published online August 3, 2019]. Arthritis Care Res. doi:10.1002/acr.24038