Original articleIncidence of tuberculosis in patients with rheumatoid arthritis. A systematic literature review
Introduction
TNFα antagonist therapy has radically changed the management of patients with rheumatoid arthritis (RA). TNFα antagonists not only alleviate the symptoms of RA, but also prevent the development of joint damage and deformities. TNFα is a pivotal factor in the inflammatory, anti-tumor, and anti-infectious immune responses. During tuberculosis, TNFα plays a crucial role in the development of the granulomas that limit lesion extension [1].
Early cohort studies showed an excess risk of tuberculosis in TNFα antagonist-treated RA patients. This finding rapidly prompted the development of recommendations about the screening and treatment of latent tuberculosis and the management of active tuberculosis during TNFα antagonist therapy. In France, the first set of recommendations was issued in 2002 by the Agency for Healthcare Product Safety (AFSSAPS) [2]. Active surveillance registries established in several countries provided additional information on the risk of tuberculosis associated with TNFα antagonists. In contrast, few epidemiological data are available on the risk of tuberculosis in RA patients before the introduction of TNFα antagonists.
The objectives of this systematic literature review were to evaluate the incidence and risk of tuberculosis in RA patients with or without exposure to TNFα antagonists, the time to the diagnosis of tuberculosis with each type of TNFα antagonist, and the proportion of extrapulmonary cases.
Section snippets
Methods
We conducted a systematic literature review by searching the Medline database using the terms tuberculosis (MeSH) and arthritis, rheumatoid (MeSH). Limits were “humans” and “French” or “English” language. We selected retrospective and prospective studies published after January 2003 in which patients met American College of Rheumatology (ACR) criteria for RA and tuberculosis cases were documented by bacteriological studies. Only studies done in Western countries or Japan were considered.
We used
Results of the literature search
Of the 709 publications retrieved by the literature search, 14 were selected. Fig. 1 shows the flow chart of article selection. Publications excluded based on the titles and abstracts were case-reports, therapeutic guidelines, and studies whose main objective was not relevant to tuberculosis.
Incidence of tuberculosis in the general population
Fig. 2 shows WHO data on the incidence of tuberculosis in the general population in various countries.
Incidence and relative risk of tuberculosis in patients with rheumatoid arthritis
Before the introduction of TNFα antagonists, few epidemiological data were obtained about the incidence
Discussion
Few data on the epidemiology of tuberculosis among RA patients were obtained before the advent of TNFα antagonists. Several studies showed a 2-fold to 10-fold increase in the risk of tuberculosis among RA patients naive to TNFα antagonists, compared to the general population [6], [7], [12]. In patients on TNFα antagonist therapy, the risk was increased 2-fold to 4-fold [12], [16].
The increase in the risk of tuberculosis seems greater with the monoclonal antibodies to TNFα than with the soluble
Conflicts of interest statement
T. Schaeverbeke contributed to clinical trials sponsored by Wyeth, Abbott, Schering, MSD, and Pfizer; occasionally produced expert reports for Abbott and Wyeth; occasionally actes as a consultant for Wyeth, Abbott, Schering, MSD, and Pfizer; and participated in conferences sponsored by Wyeth, Pfizer, MSD, Abbott, and Schering.
C. Richez contributed to clinical trials sponsored by Wyeth, Abbott, Schering, MSD, and Pfizer; and occasionally produced expert reports for Wyeth-Pfizer.
References (27)
- et al.
Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management
Lancet Infect Dis
(2003) - et al.
Tuberculosis and infliximab treatment. National surveillance from January 1, 2000, through June 30, 2003 [Article in French]
Presse Med
(2005) - et al.
Infections induced by low-dose corticosteroids in rheumatoid arthritis: a systematic literature review
Joint Bone Spine
(2010) - et al.
Anti-TNFalpha blockers, autoantibodies and autoimmune diseases
Joint Bone Spine
(2009) - et al.
Prospective cohort study of effects of infliximab on rheumatoid factor, anti-cyclic citrullinated peptide antibodies and antinuclear antibodies in patients with long-standing rheumatoid arthritis
Joint Bone Spine
(2009) Prévention et prise en charge des tuberculoses survenant sous anti-TNF
Afssaps
(2005)Epidemiologie de la tuberculose en France et en Europe
sanitaire Idv
(2006)Surveillance, planning, financing
WHO Organization
(2008)- et al.
Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy
Arthritis Rheum
(2004) - et al.
Increased risk of tuberculosis in patients with rheumatoid arthritis
J Rheumatol
(2003)
Increased risk of tuberculosis in patients with rheumatoid arthritis in Japan
Ann Rheum Dis
Rheumatoid arthritis, its treatments, and the risk of tuberculosis in Quebec, Canada
Arthritis Rheum
Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists
Arthritis Rheum
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