Increased Risk of Surgery After Attenuation of Anti-Tnfα Therapy for Crohn’S Disease
Brian P. Bosworth*1, Benjamin Lebwohl2, Raja Taunk3, Nicole Green1, Harrison Lakehomer1, Ugonna Iroku2, Arun Swaminath2, Jeffrey W. Milsom4, Fabrizio Michelassi4, Ellen J. Scherl1
1Gastroenterology and Hepatology, Weill Medical College of Cornell University, New York, NY; 2Digestive and Liver Diseases, Columbia College of Physicians and Surgeons, New York, NY; 3Medicine, New York Presbyterian Hospital: Weill Cornell Center, New York, NY; 4Surgery, Weill Medical College of Cornell University, New York, NY
Background: The rate of intestinal resection among patients with Crohn’s disease may be as high as 80% after 20 years of disease. By inducing mucosal healing and achieving high remission rates, TNFα antagonists reduce hospitalizations and steroid requirement. Early combination treatment with azathioprine (AZA) and anti-TNFα achieves higher remission rates than either infliximab (IFX) or AZA alone. It is presumed that IFX, adalimumab (ADA) and certolizumab (CZP) will also impact on the need for surgery. However, many patients attenuate response or flare during therapy, requiring re-induction or switch among anti-TNFs. When this fails, surgery becomes necessary. The goal of our study was to identify risk factors for surgery in the setting of biologic therapy. Methods: The Consortium on Outcomes of Biologic Therapy in IBD (COBI) is a prospectively compiled database of 147 patients treated for Crohn’s disease between July 2002 and September 2009 with anti-TNFα medications (for a total of 366 patient-years of therapy). We performed a retrospective analysis to determine the incidence and risk of TNFα antagonist attenuation of response or need for surgical intervention. Both univariate and multivariate analyses were performed.Results: In our cohort, 63% of patients were either re-induced with (16/93, 17%) or switched to a second TNFα antagonist (77/93, 83%). Surgery had been performed in 38% of these patients prior to anti-TNFα therapy. The mean age at the start of the first anti-TNFα was 33.5 (± 15.2) years; mean duration of disease 9.2 (± 9) years and mean duration of initial anti-TNFα treatment 36.1 (±31.2) months. There were 82, 9 and 2 patients initially started on IFX, ADA and CZP respectively; the second agent used was IFX, ADA and CZP in 1, 55 and 21 patients respectively. There were 31 patients (33%) who underwent surgery within 6 months of failing the initial regimen. Patients treated with anti-TNFα therapy for longer periods (>30 months) had increased odds of surgery (OR 3.22, 95% CI 1.03-10.06).Conclusion: Despite the efficacy of the TNFα antagonists, nearly 2/3 of patients required either re-induction or switch within the class, with surgery necessary in nearly 1/3 of those patients. Patients on long-term anti-TNFα therapy before switching had a greater risk for surgery. Earlier intervention with primary anti-TNFα therapy may decrease secondary loss of response and intestinal resection rates. Further studies are warranted to determine anti-TNFα optimization strategies and whether attenuation is less likely among different anti-TNFα agents.
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