The overall risk for infection in patients with rheumatoid arthritis (RA) who are treated with nontumor necrosis factor (TNF) inhibitors is highest among those treated with rituximab compared with abatacept and tocilizumab, according to study results published in Rheumatology.

According to researchers, the risk for infection and the identification of risk factors may be important when choosing non-TNF inhibitor biologic disease-modifying antirheumatic drugs (bDMARDs) for patients with RA. However, few studies have investigated this topic in this patient population. The objective of this study was to compare incidence rates and overall infection risk for Danish patients with RA who initiated therapy with abatacept, rituximab, or tocilizumab and to determine whether smoking, age, use of prior bDMARDs, or other clinical characteristics increased the risk for infection.

In this observational cohort study, researchers identified all patients with RA from the Danish DANBIO registry, which collects prospective data on adults with rheumatic disease treated with bDMARDs. Patients were included in the study if they initiated treatment with abatacept, tocilizumab, or rituximab between 2010 and 2017 as a first-line treatment or had a history of treatment with another bDMARD. Infections were defined as hospitalization due to infection during treatment with a non-TNF inhibitor bDMARD or as reimbursement of an antibiotic prescription, whichever came first. Incidence rates of infection for each drug were adjusted for age and gender using Poisson regression analyses.

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Researchers revealed there were 3696 treatment courses of non-TNF inhibitor bDMARD in 2716 unique patients: 1115 courses of abatacept, 1017 courses of rituximab, and 1564 courses of tocilizumab. Patients treated with rituximab were likely to be older, have longer disease duration, and have previous history of cancer, whereas patients treated with tocilizumab had higher C-reactive protein levels.

During the first 12 months after treatment initiation, 1747 infections were recorded: 512 with abatacept, 500 with rituximab, and 735 with tocilizumab. Age and gender-adjusted incidence rates per 100 person-years were 76 (95% CI, 69-84) for abatacept, 87 (95% CI, 79-96) for rituximab, and 77 (95% CI, 71-84) for tocilizumab. Adjusted relative risk was 0.94 (95% CI, 0.81-1.08) for abatacept, 0.94 (95% CI, 0.81-1.03) for tocilizumab compared with rituximab, and 1.00 (95% CI, 0.88-1.14) for abatacept compared with tocilizumab. A relative risk of approximately 1 was observed after 24 months. Patients with a history of treatment with another bDMARD and ever-smokers had an increased risk for infections compared with patients who were biologics-naive and never-smokers.

Limitations to this study were as follows: missing data may have led to information bias, and the study’s observational design may have led to residual confounding. 

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The study researchers concluded that patients with RA may experience+ a higher risk for infection when treated with rituximab; patients most prone to infections with abatacept, rituximab, or tocilizumab tended to be older, ever-smokers, or have a history of prior treatment with another bDMARD.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Grøn KL, Glintborg B, Nørgaard M, et al. Overall infection risk in rheumatoid arthritis during treatment with abatacept, rituximab and tocilizumab; an observational cohort study [published online November 25, 2019]. Rheumatology. doi: 10.1093/rheumatology/kez530