P297. Efficacy and safety of natalizumab in Crohn's disease patients treated at six academic Boston hospitals
P. Juillerat1, S.K. Wasan2, S. Fowler3, P. Vikas4, S. Friedman4, J.A. Coukos2, K. Germansky5, A. Barto6, R. Pellish7, A. Cheifetz5, J.R. Korzenik3, F.A. Farraye2, V. Yajnik3
1Inselspital, University Hospital Bern, University Clinic for Visceral Surgery and Medicine, Gastroenterology, Bern, Switzerland; 2Boston University School of Medicine, Gastroenterology, Boston, United States; 3Massachusetts General Hospital, GI Unit, Boston, United States; 4Brigham and Women's Hospital, Gastroenterology, Boston, United States; 5Beth Israel Deaconess Medical Center, Gastroenterology, Boston, United States; 6Lahey Clinic, Gastroenterology, Burlington, United States; 7University of Massachusetts, Gastroenterology, Boston, United States
Background: Despite trials demonstrating its efficacy, many physicians harbor concerns regarding the use of natalizumab in the treatment of patients with refractory Crohn's disease (CD). The purpose of this study was to perform a descriptive analysis of a series of CD patients not enrolled in a clinical trial who received natalizumab (N).
Methods: Patients (pts) on N were identified from the following six sites in Massachusetts: Boston Medical Center (8, 12%), Beth Israel Deaconess Medical Center (9, 13%) Brigham and Women's Hospital (8, 12%), Lahey Clinic (6, 8%), Massachusetts General Hospital (36, 52%) and UMass Medical Center (2, 3%). A retrospective chart review was performed to collect demographic data, disease characteristics, prior medications, duration of N use and reasons for stopping.
Results: 69 patients on N were identified, of whom 68% were female and 93% were white. The average age (±SD, range) at the start of N was 35.1 years (±11, 1966), by which time pts had CD for 11.9 years (±8, 144). 70% had ileocolonic, 24% had colonic, and 6% ileal disease. In addition, 14% had upper GI involvement and 65% had perianal disease, 8 of whom had diverting ileostomies. Other prior surgeries were bowel resection (57% of all patients) and fistula surgery (26%). Prior non-biologic therapies were steroids (96%), 6MP/AZA (94%), antibiotics (74%) and MTX (58%). All but 4 pts had tried and failed anti‑TNF agents: 16 failed 3, 39 failed 2 and 10 failed 1. 18 patients (37%) were primary non responders (after 4 infusions, range 19), 10 (13%) lost efficacy (about 10.7 inf, 614), 6 had an allergic reaction (half ≤3 inf and half ≥8 inf, range 121), 10 for other reasons (adverse events (AE), patient request or medical advice). 25 were still maintained on N with an average of 14 (± 10, 241) inf. Durations of active treatments are currently <1 y (13 pts), 12ys (8 pts) and >2ys (4 pts). The most frequent AE were allergic reactions, headaches, fever and infections (herpes zoster, sore throat, perianal and abdominal abscess). No case of progressive multifocal leucoencephalopathy was observed.
Conclusions: In our clinical experience outside clinical trials, it is largely reserved for CD patients with extensive ileocolonic disease with associated perianal and upper GI involvement and who have failed conventional immunosuppressants and at least two anti‑TNF alpha agents. Natalizumab is well tolerated and offers significant clinical improvement for more than 1 year in one third of these difficult-to-treat CD patients.