RESEARCH - Drug-specific risk of non-TB infections in patients receiving anti-TNF therapy: RATIO

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Ann Rheum Dis 2011;70:616-623 doi:10.1136/ard.2010.137422

Clinical and epidemiological research

Extended report

Drug-specific risk of non-tuberculosis opportunistic infections in

patients receiving anti-TNF therapy reported to the 3-year prospective

French RATIO registry

D Salmon-Ceron1, F Tubach2, O Lortholary3, O Chosidow4, S Bretagne5, N

Nicolas2, E Cuillerier6, B Fautrel7, C Michelet8, J Morel9, X

Puéchal10, D Wendling11, M Lemann12, P Ravaud13, X Mariette14, for the

RATIO group

1Université Paris Descartes Assistance Publique–Hôpitaux de Paris

(AP-HP), Hôpital Cochin Broca Hôtel Dieu, Unité de Maladies

Infectieuses, Pôle de médecine, Paris, France

2Université Paris 7 Denis Diderot, UFR de médecine; INSERM, U738;

INSERM CIE801; AP-HP, Hôpital Bichat, Département d'Epidémiologie,

Biostatistique et Recherche Clinique, Paris, France

3Université Paris Descartes; AP-HP, Hôpital Necker-Enfants malades,

Service de maladies infectieuses et tropicales, Centre d'Infectiologie

Necker-Pasteur, Paris, France

4Université Paris-EST; AP-HP, Hôpital Henri Mondor, Service de

dermatologie, Paris, France

5Université Paris-EST; AP-HP, Hôpital Henri Mondor, Service de

parasitologie-mycologie, Créteil, France

6Centre Hospitalier Général, Service de gastro-entérologie, Dreux, France

7Université Paris 6 - Pierre et Marie Curie, UFR de Médecine; AP-HP,

Hôpital Pitié-Salpétrière, Service de rhumatologie, Paris, France

8Université Rennes 2, Hôpital Pontchaillou, Service des maladies

infectieuses et réanimation médicale, Rennes, France

9Université de Montpellier; Hôpital Lapeyronie, Service

d'immuno-rhumatologie, Montpellier, France

10Hôpital du Mans, Service de rhumatologie, Le Mans, France

11Université de Franche Comté; Hôpital Minjoz, Service de

rhumatologie, Besançon, France

12Université Paris 7 Denis Diderot, AP-HP, Hôpital Saint Louis,

Service de gastro-entérologie, Paris, France

13Université Paris Descartes; INSERM, U738; AP-HP, Hôpital Cochin

Broca Hôtel Dieu, Centre d'épidémiologie clinique et de médecine basée

sur les preuves, Paris, France

14Université Paris-Sud 11, AP-HP, Hôpital Bicêtre, Service de

rhumatologie; INSERM, U1012, Le Kremlin-Bicêtre, France

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.

http://ard.bmj.com/content/70/4/616.abstract

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