RESEARCH - Orencia (abatacept) does not exacerbate chronic Mycobacterium tuberculosis infection in mice

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Arthritis Rheum. 2007 Aug;56(8):2557-65.

Abatacept treatment does not exacerbate chronic Mycobacterium

tuberculosis infection in mice.

Bigbee CL, Gonchoroff DG, Vratsanos G, Nadler SG, Haggerty HG, Flynn JL.

University of Pittsburgh School of Medicine, 200 Lothrop Street,

Pittsburgh, PA 15261, USA.

OBJECTIVE: Treatment of rheumatoid arthritis and other autoimmune

disorders with anti-tumor necrosis factor (anti-TNF) agents is

associated with an increased risk of reactivation of latent

Mycobacterium tuberculosis. While the mechanism of action of abatacept

is fundamentally different from that of anti-TNF therapies, its effect

on the protective response to latent tuberculosis is not known. We

undertook this study to determine the effect of abatacept treatment in

a murine model of chronic M tuberculosis infection. METHODS: Chronic M

tuberculosis infection was established in C57BL/6 mice. Four months

after infection, mice were treated for up to 16 weeks with abatacept,

anti-murine TNF antibody, or vehicle. The primary end point was

survival; body weight, bacterial load, histologic features,

interferon-gamma (IFNgamma) production by T cells, and cellular

infiltration were also assessed. RESULTS: Abatacept- and

vehicle-treated groups both maintained control of M tuberculosis

infection, with 100% survival after 16 weeks of treatment. These 2

groups had no significant differences in body weight, no clinically

relevant differences in bacterial load in the lungs, lymph nodes, or

spleen, and no differences in the mean percentage of total or

activated T cells, macrophages, neutrophils, or B cells, or in

IFNgamma production in the lung or lymph nodes. In contrast, 100%

mortality was seen in the anti-TNF antibody-treated group by week 9,

with significant body weight loss and increased bacterial load in the

lungs, lymph nodes, and spleen. Furthermore, the anti-TNF

antibody-treated group had increased pathology consistent with the

exacerbation of M tuberculosis infection.

CONCLUSION: Abatacept did not impair the ability of mice to control a

chronic M tuberculosis infection. In contrast, mice treated with

anti-TNF therapy showed increased pathology and bacterial load, with

100% mortality by week 9. The clinical significance of these findings

has not yet been determined.

PMID: 17665452

http://www.ncbi.nlm.nih.gov/pubmed/17665452

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