Infliximab or Cyclosporine for Severe Ulcerative Colitis

Abstract

The editorial by D’Haens provides an excellent background and review of the roles for cyclosporine and infliximab in ulcerative colitis (UC).1D’Haens G. Infliximab for ulcerative colitis finally some answers.Gastroenterology. 2005; 128: 2161-2164Abstract Full Text Full Text PDF Scopus (27) Google Scholar However, the “cards are not all in” yet regarding the “impact,” or should we say, “positioning” of infliximab versus cyclosporine for ulcerative colitis. I agree with D’Haens that the ACT I and ACT 2 trials demonstrate effectiveness for patients with “active disease, despite corticosteroid, and immunomodulator treatment” and even (ACT 2) for patients failing aminosalicylates therapy. Indeed, future trials should consider a “top down” approach with infliximab versus corticosteroids for aminosalicylates refractory UC. The positioning of infliximab versus cyclosporine in severe, steroid-refractory UC is not as clear-cut. While the Janerot study2Jarnerot G. Hertervig E. et al.Infliximab as rescue therapy in severe to moderately severe ulcerative colitis a randomized, placebo-controlled study.Gastroenterology. 2005; 128: 1805-1811Abstract Full Text Full Text PDF Scopus (915) Google Scholar demonstrated short-term benefits from infliximab in a severe, steroid-refractory population, the Probert study3Probert C.S. Hearing S.D. et al.Infliximab in moderately severe glucocorticoid resistant ulcerative colitis a randomised controlled trial.Gut. 2003; 52: 998-1002Google Scholar was substantially less impressive in a similar cohort. The combined, or even Janerot, alone, data are not as consistent as the data for cyclosporine in the same context, as D’Haens has reviewed. Furthermore, the potential positioning of therapy (cyclosporine or infliximab, first) has a significant implication for steroid-refractory patients. If infliximab is administered to patients with severe, steroid-refractory UC the drug, and its immunosupressive properties will be present for nearly a month (half-life ∼9 days; Remicade, Centocor, package insert). If the patient fails therapy and wishes to consider cyclosporine rescue, we have no data to support the safety of combined anti-TNF and cyclosporine immunotherapy. Conversely, while we have no data regarding the salvage potential of infliximab in cyclosporine-refractory patients, discontinuing cyclosporine and administration of infliximab would not have the same pharmacodynamic issues pertaining to concomitant exposure. Despite D’Haens’ comments regarding the shortcomings of cyclosporine therapy, the agent has been consistently efficacious in the setting of severe, UC, whether steroid-refractory, or not and there is consistent data regarding long-term transitioning to azathioprine or mercaptopurine to maintain the inductive benefits.4Cohen R.D. Stein R. et al.Intravenous cyclosporin in ulcerative colitis a five-year experience.Am J Gastroenterol. 1999; 94: 1587-1592Google Scholar, 5Actis G.C. Bresso F. et al.Safety and efficacy of azathioprine in the maintenance of ciclosporin-induced remission of ulcerative colitis.Aliment Pharmacol Ther. 2001; 15: 1307-1311Google Scholar While we are all excited and impressed with the data for infliximab in UC, the ultimate positioning remains to be established, particularly in the setting of hospitalized patients with severe UC. Hopefully, clinical trials comparing the short and long-term strategies of infliximab and cyclosporine for severe UC will be forthcoming along with trials evaluating a “top-down” strategy comparing the benefits of infliximab versus corticosteroids for aminosalicylates-refractory disease. It would be most helpful to identify biomarkers or other predictors of response to individual therapies in each of these settings. ReplyGastroenterologyVol. 129Issue 4PreviewWe appreciate Hanauer’s remarks regarding the positioning of cyclosporin versus infliximab for severe steroid refractory ulcerative colitis. It will indeed require a controlled clinical trial to settle the issue which of the 2 treatments should be used first when steroids fail. We need to acknowledge, however, that in the majority of patients cysclosporin needs to be administered during prolonged hospitalization. In addition, the long-term benefit of the treatment is far from satisfacory: Moskowitz et al recently reviewed the patient cohort treated with cyclosporin at the University of Leuven and reported that only 12 per cent had avoided colectomy after 7 years of follow-up. Full-Text PDF Infliximab or Cyclosporine for Severe Ulcerative ColitisGastroenterologyVol. 130Issue 1PreviewI read with interest Dr. Hanauer’s letter on infliximab or cyclosporine for severe ulcerative colitis (UC).1 We certainly need more studies with both drugs in UC. Controlled studies of infliximab in corticosteroid-resistant UC are few, and with cyclosporine even fewer. Dr. Hanauer makes a mistake when he compares our study2 with the Probert study.3 In the latter study, patients were included if they failed to respond to conventional treatment with glucocorticoids, and were not in need of urgent colectomy. Full-Text PDF