Can infliximab increase the risk of tuberculosis?/nThis question concerns an 87-year-old woman trea

Fråga: Can infliximab increase the risk of tuberculosis?

This question concerns an 87-year-old woman treated with infliximab for reumatoid arthritis. Three weeks after her second infusion she is taken to hospital with fever and pulmonary infiltrates are seen on X-ray. Miliary tuberculosis is suspected and she is treated with antituberculosis drugs. After three months of treatment she dies. Autopsy shows suspected miliary tuberculosis involving lungs, liver and spleen.

Sammanfattning: Infliximab does increase the risk of active tuberculosis.

Svar: Infliximab is a tumour necrosis factor alpha (TNF alpha) inhibitor that is used to treat reumatologic diseases and Crohns disease (1). TNF alpha is a cytokine that enhances the ability of macrophages to phagocytose and kill mycobacteria, like Mycobacterium tuberculosis (2).

The risk of active tuberculosis is increased in patients treated with infliximab and an unusually high proportion of the patients with tuberculosis have extrapulmonary or disseminated tuberculosis (3). In many of these patients tuberculosis seems to be caused by reactivaton of latent tuberculosis (2).

The incidence of tuberculosis in Spanish patients with reumatoid arthritis treated with infliximab was 1893 per 100000 patients year 2000 and 1113 per 100000 patients year 2001. Background incidence was 21 cases per 100000 inhabitants and among RA patients not exposed to TNF inhibitors the incidence was 95 cases per 100000 patients. Fifty-nine per cent of patients with TB were diagnosed within 3 months after initiation of infliximab tratment and the infection was extrapulmonary in 65% of patients (4).

In Vigibase, WHO:s adverse drug reactions database, there are 148 reports of tuberculosis following infliximab treatment (5) and in the files of SADRAC (Swedish Adverse Drug Reactions Advisory Committee) there are four reports of tuberculosis (6).

Before treatment with infliximab is initiated all patients should be screened for active and latent tuberculosis infection according to the Swedish Medical Products Agency (MPA) (7). 1 FASS 2003 (The Swedish catalogue of approved medical products) 2 Long R, Gardam M. Tumour necrosis factor-alpha inhibitors and the reactivation of latent tuberculosis infection. CMAJ 2003;168(9):1153-6. 3 Arend SM, Breedveld FC, van Dissel JT. TNF-alpha blockade and tuberculosis: better look before you leap. Neth J Med 2003;61(4):111-9. 4 Gomez-Reino JJ, Carmona L, Valverde VR, Mola EM et al. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk. A multicenter active-surveillance report. Arthritis Rheum 2003;48(8):2122-7. 5 Vigibase: WHO:s adverse drug reactions database (2003-09-02) 6 Swedis (The Swedish Drug Information System) (2003-09-02) 7 Remicade - viktig uppdatering av säkerhetsinformation. Läkemedelsverket Uppdaterad 2002-02-01.