Serious infective complications associated with anti-TNF alpha therapy in inflammatory bowel disease

Abstract

Background: Anti-TNFαmedications are effective in the management of patients with difficult Crohn’s disease (CD) and ulcerative colitis/IBDU(UC/IBDU). They are, however, associated with an increased risk of tuberculosis (TB) reactivation, initial TB infection, and potentially other bacterial, viral or fungal infections. Aims: To examine the Australasian experience of TB and serious infective complications in IBD patients treated with an anti-TNFα. Methods: Data was collected from eight sites across Australia and New Zealand specialising in IBD management. Overall IBD patient numbers managed, patient numbers ever treated with an anti-TNFα, and patients suffering TB, or a serious infection while receiving anti-TNFαtherapy were analysed. A serious infection was defined as ‘an infection requiring hospital admission’. Patient demographics, concurrent IBD medications, the anti-TNFαmedication used, time on the anti-TNFα, infection type and infection outcome was also collected. Results: A total of 5613 IBD patients (2904 CD, 2709 UC/IBDU) were managed across the centers. Anti-TNFαtherapy was used in 16.9% of CD(491; 442-infliximab, 94-adalimumab, 45-both) and 3.7% of UC/IBDU patients (100 UC/IBDU; 94-infliximab, 14-adalimumab, 8-both). There were no cases of reactivation of latent TB and no new cases reported. There were nine serious infections (4M/5F, 1 UC/IBDU/8 CD, average 36.1 years, range 14–57 years). Infections occurred in three patients receiving <6months, one with 6–12 months, three after 12–24 months and two with >24 months of an anti-TNFα. All these patients were receiving additional immunosuppressive (IS) medication: 2-pred, 1-pred/AZA, 2-AZA, 1-methotrexate (MTX), 1-pred/MTX, 1-pred/AZA/MTX and 1-pred/MTX/mycophenolate mofetil. Seven of the infections occurred while on an anti-TNFαand two within 3 months of the last treatment. There were two primary varicella zoster, one Pneumocysits carnii peunmonia, one UTI with enterobacteraerogenes, and five infections where no organ-ism was identified (1 pneumonia, one diverticular abscess, one conjunc-tivitis and two unidentified source). All infections resolved. Conclusion: TB does not appear to be a problem with anti-TNFα therapy in Australasia. Infections, resulting in a hospital admission, are low occur-ring in only 1.8% of patients receiving anti-TNFαtherapy, but all those patients were also on other IS medications. All the infections were successfully treated.