Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three-year prospective French Research Axed on Tolerance of Biotherapies registry.

Abstract

OBJECTIVE:

Tuberculosis (TB) is associated with anti-tumor necrosis factor (anti-TNF) monoclonal antibody (mAb) therapy, but whether this association is drug-specific remains a concern. Our objective was to describe cases of TB associated with anti-TNF mAb therapy, identify risk factors, and estimate the incidence.

METHODS:

We conducted an incidence study and a case-control analysis to investigate the risk of newly diagnosed TB associated with the use of anti-TNF agents. As part of the French Research Axed on Tolerance of Biotherapies (RATIO) registry, for 3 years we collected cases of TB among French patients receiving anti-TNF mAb therapy for any indication; for each case, 2 patients treated with anti-TNF agents served as control subjects.

RESULTS:

We collected 69 cases of TB in patients treated for rheumatoid arthritis (n = 40), spondylarthritides (n = 18), inflammatory colitis (n = 9), psoriasis (n = 1) and Behçet's disease (n = 1) with infliximab (n = 36), adalimumab (n = 28), and etanercept (n = 5). None of the patients had received correct chemoprophylactic treatment. The sex- and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The standardized incidence ratio (SIR) was 12.2 (95% confidence interval [95% CI] 9.7-15.5) and was higher for therapy with infliximab and adalimumab than for therapy with etanercept (SIR 18.6 [95% CI 13.4-25.8] and SIR 29.3 [95% CI 20.3-42.4] versus SIR 1.8 [95% CI 0.7-4.3], respectively). In the case-control analysis, exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB (odds ratio [OR] 13.3 [95% CI 2.6-69.0] and OR 17.1 [95% CI 3.6-80.6], respectively). Other risk factors were age, the first year of anti-TNF mAb treatment, and being born in an endemic area.

CONCLUSION:

The risk of TB is higher for patients receiving anti-TNF mAb therapy than for those receiving soluble TNF receptor therapy. The increased risk with early anti-TNF treatment and the absence of correct chemoprophylactic treatment favor the reactivation of latent TB.

• Authors: F Tubach, D Salmon, P Ravaud, Y Allanore, P Goupille, M Bréban, B Pallot-Prades, S Pouplin, A Sacchi, R M Chichemanian, S Bretagne, D Emilie, M Lemann, O Lortholary, O Lorthololary, X Mariette, Research Axed on Tolerance of Biotherapies Group
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 60 Issue 7 Pg. 1884-94 (Jul 2009) ISSN: 0004-3591 [Print] United States
• PMID: 19565495 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Immunoglobulin G
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha
• Infliximab
• Adalimumab
• Etanercept

Topics

• Adalimumab
• Adult
• Aged
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Arthritis, Rheumatoid (drug therapy)
• Behcet Syndrome (drug therapy)
• Case-Control Studies
• Colitis (drug therapy)
• Etanercept
• Female
• France
• Humans
• Immunoglobulin G (adverse effects, therapeutic use)
• Infliximab
• Male
• Middle Aged
• Prospective Studies
• Receptors, Tumor Necrosis Factor (therapeutic use)
• Registries
• Risk Factors
• Spondylarthritis (drug therapy)
• Treatment Outcome
• Tuberculosis (chemically induced, drug therapy, epidemiology)
• Tumor Necrosis Factor-alpha (immunology)