Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry.

Abstract

BACKGROUND:

Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs).

OBJECTIVE:

To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their risk factors.

METHODS:

A 3-year national French registry (RATIO) collected all cases of OI in patients receiving anti-TNF treatment for any indication in France. A case-control study was performed with three controls treated with anti-TNF agents per case, matched for gender and underlying inflammatory disease.

RESULTS:

45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26), spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4 nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4 disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3 invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2 leishmaniasis). Ten patients (23%) required admission to the intensive care unit, and four patients (9%) died. Risk factors for OIs were treatment with infliximab (OR=17.6 (95% CI 4.3 - 72.9); p<0.0001)or adalimumab (OR=10.0 (2.3 to 44.4); p=0.002) versus etanercept, and oral steroid use >10 mg/day or intravenous boluses during the previous year (OR=6.3 (2.0 to 20.0); p=0.002).

CONCLUSION:

Various and severe OIs, especially those with intracellular micro-organisms, may develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody rather than soluble TNF receptor therapy and steroid use >10 mg/day are independently associated with OI.

• Authors: D Salmon-Ceron, F Tubach, O Lortholary, O Chosidow, S Bretagne, N Nicolas, E Cuillerier, B Fautrel, C Michelet, J Morel, X Puéchal, D Wendling, M Lemann, P Ravaud, X Mariette, RATIO group
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 70 Issue 4 Pg. 616-23 (Apr 2011) ISSN: 1468-2060 [Electronic] England
• PMID: 21177290 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Immunoglobulin G
• Immunologic Factors
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha
• Infliximab
• Adalimumab
• Etanercept

Topics

• Adalimumab
• Adult
• Aged
• Anti-Inflammatory Agents (adverse effects)
• Antibodies, Monoclonal (adverse effects)
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents (adverse effects)
• Epidemiologic Methods
• Etanercept
• Female
• France (epidemiology)
• Humans
• Immunoglobulin G (adverse effects)
• Immunologic Factors (adverse effects)
• Infliximab
• Male
• Middle Aged
• Opportunistic Infections (chemically induced, epidemiology)
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)