Incidence density of serious infection, opportunistic infection, and tuberculosis associated with biologic treatment in patients with rheumatoid arthritis – a systematic evaluation of the literature

Trung N Tran,¹ Herve Caspard,¹ Fabio Magrini<sup>2

1</sup>Clinical Development, MedImmune, Gaithersburg, MD, USA; ²Eli Lilly, San Diego, CA, USA

Abstract: Summary data on the incidence density (ie, incidence per person-year [PY]) of serious infection, opportunistic infection, and tuberculosis associated with each of the nine biologic therapies currently indicated in rheumatoid arthritis patients are not available. To summarize these data, a systematic review was conducted with searches on PubMed and Embase of literature ranging from January 1998 to November 2011. Incidence density was extracted and reported using the definitions from the respective publications. If the incidence density was not reported, estimation was made using available information. A total of 72 published studies met the inclusion criteria and were reviewed, including 44 clinical trials, open-label extension studies, or meta-analyses, and 28 observational studies. Additional calculation of the incidence density was performed in 12 studies for serious infection and in 13 studies for opportunistic infection or tuberculosis. The incidence of serious infection was consistent across studies and biologic therapies, ranging from 0 to 11/100 PY but mainly clustered from 2 to 6/100 PY. Fewer incidence data were available for opportunistic infection and tuberculosis. The incidence of opportunistic infection and tuberculosis ranged widely, from 0.01 to 3.0/100 PY and 0.01 to 2.6/100 PY, respectively. The data on serious infection may be used to evaluate the public health risk and benefit of biologic treatment. They may also serve as a point of reference for future studies. The limited data on opportunistic infection and the lack of a consistent definition of opportunistic infection invite caution for a benchmark rate for opportunistic infection as a composite category.

Keywords: DMARD, biologic, review, safety, infection, adverse event