Infliximab for Crohnʼs Disease: The First 262 Patients, Ten Years Later (2009)

Purpose: To evaluate the long-term safety profile and usage patterns of infliximab in patients (pts) with Crohn's disease. Methods: From 1998-2001 262 pts received at least 1 infliximab infusion. The medical records of these pts were reviewed and abstracted for adverse events and length of treatment. Results: There were 194 pts who received induction and 68 pts who received maintenance therapy during initial infliximab courses. Of the 194 pts started on induction therapy, 22 received maintenance infliximab during subsequent treatments. Seventy pts had >1 time period during which infliximab was infused with a total of 90 pts having received maintenance therapy. Over the past 10 years (yrs), 55/90 pts receiving maintenance therapy required dose escalation and/or shortened dosing interval. The median follow-up after first infusion was 7.2 yrs (range, 0.01-10.7 yrs). The cumulative probability of any bacterial complication at 30 days, 1 yr, 5 yrs and 10 yrs was 1%, 7%, 34% and 39%, respectively. There were 28 bacterial infections, including Mycobacterium avium intracellulare complex (n=1), C. difficile (n=1), bacteremia (n=11), abscess (n=4), Staphylococcus (n=2), and other (n=9). The cumulative probability of any fungal infection at 30 days, 5 yrs and 10 yrs was 0.5%, 9% and 9%, respectively. There were 5 fungal infections, including histoplasmosis (n=3), and candidiasis (n=2). The cumulative probability of any viral infection at 30 days, 1 yr, 5 yrs and 10 yrs was 1%, 3%, 7% and 10%. There were 8 viral infections (herpes simplex or varicella zoster). The cumulative probability of malignancy at 30 days, 1 yr, 5 yrs and 10 yrs was 1%, 3%, 7% and 14%. There were 12 documented cases of cancer and dysplasia including lymphoma (n=1), squamous cell skin carcinoma (n=1), melanoma (n=1), lung adenocarcinoma (n=2) and dysplasia (n=7). Of 262 pts, 30 had an infusion reaction, 30 had a delayed hypersensitivity reaction, and 7 had a lupus reaction. Of the 68 pts who received maintenance therapy during the initial course of treatment with infliximab, the cumulative probability of discontinuation was 60.3% at 5 yrs and 91.2% at 10 yrs. Maintenance therapy was discontinued in 25/90 pts secondary to loss of response with an additional 23 pts discontinuing for other reasons. Based on 24 pts the cumulative probability of death at 5yrs and 10yrs was 8% and 15%. Conclusion: In our early clinical practice with infliximab for Crohn's disease, the persistency rate among those treated with maintenance therapy was 40% at 5 years and 9% at 10 years. The long-term safety of infliximab remained consistent with current knowledge. Adverse events observed include bacterial, fungal, and viral infections, infusion and autoimmune reactions, and malignancy. Disclosure: Jennifer Seminerio: No financial relationships Dr Edward V. Loftus, Jr - Consultant:Abbott Labs and UCB and Schering - Plough, consulting for Abbott Labs and UCB Dr William J. Sandborn - consultant: Research support and consultant - Centocor, Abbott Laboratories, UCB Pharma, Schering-Plough W. Scott Harmsen: No Financial Relationships Prabin Thapa: No Financial Relationships Alan R. Zinsmeister: No Financial Relationships.