Incidence of tuberculosis in patients with rheumatoid arthritis. A systematic literature review

Objectives: To determine the incidence and risk of tuberculosis in rheumatoid arthritis (RA) patients exposed or unexposed to TNFα antagonists, the impact of recommendations about managing latent tuberculosis, the time to diagnosis of active tuberculosis, and the proportion of extrapulmonary forms.

Methods: Systematic review of articles retrieved using Medline. From each article, we abstracted the incidence and risk of tuberculosis in RA patients exposed or unexposed to TNFα antagonists, the duration of TNFα antagonist exposure at the diagnosis of tuberculosis, and the distribution of the tuberculosis foci.

Results: We selected 14 articles. The risk of tuberculosis was increased 2- to 10-fold in RA patients unexposed to TNFα antagonists and 2- to 4-fold in those exposed to TNFα antagonists, compared to the general population. The incidence of tuberculosis in TNFα antagonist-treated patients varied across studies (9.3 to 449/100,000) according to the country, observation period, and TNFα antagonist used. The risk was greater with monoclonal antibodies than with the soluble receptor. Official recommendations have decreased the risk of tuberculosis in TNFα antagonist-treated patients. Over half the cases of active tuberculosis were diagnosed during the first treatment year. Among TNFα antagonist-treated patients with tuberculosis, 60% had extrapulmonary lesions. Disseminated tuberculosis was more common with monoclonal antibodies.

Conclusions: The risk of tuberculosis is increased during TNFα antagonist therapy, and the increase is larger with the monoclonal antibodies than with the soluble receptor. Tuberculosis during TNFα antagonist therapy is a rare event that occurs early after treatment initiation. Extrapulmonary involvement is common and potentially severe. Therefore, clinicians should direct careful attention to the risk of tuberculosis associated with TNFα antagonist therapy.