Infliximab in the treatment of steroid resistant/dependant and fistulating Crohn's disease: An analysis of predictors of response in a italian multicentric open study in 573 patients
Orlando A., Colombo E., Kohn A., Biancone L., Viscido A., Sostegni R., Rizzello F., Benazzato L., Castiglione F., Papi C., Meucci G., Rigler G., Mocciaro F., Lavagna A., Molten M., Scimeca D., Angelucci E., Morselli C., Geremia A., Milite G., Cottone M.
Background: The treatment of moderate-severe Crohn's disease is difficult and approximately 20% of patients do not respond to conventional therapy, including corticosteroids and immunosuppressive drugs. Infliximab is a treatment of proven efficacy in this group of patients. It is not clear which variables predict a good response. Aims: To evaluate in a large series of patients (pts) with acute steroid resistant Crohn's Disease or fistulating disease the role of Infliximab looking at the predictors of response. Patients and Methods: 573 pts (265 men, 308 women) with steroid dependent/resistant moderate severe Crohn's disease (CDAI > 220-400) (312 pts) or with fistulating disease (190 pts) or both of them (71 pts) (perianal 72%, enterocutaneous 11%, others 17%) in 12 Italian referral centers were treated with a dose of 5 mg per kg of body weight. In dependant/resistant steroid disease one single or 3 infusions were given whereas in fistulating disease 3 infusions (at 0,2,6 weeks) were given. Primary endpoints were: (a) clinical response, defined as a reduction of 70 or more points in the score on the Crohn's disease activity index at 12 weeks after first infusion and clinical remission, defined as CDAI < 150 in pts with steroid/dependant patients; (b) reduction of at least 50% of the number of fistulas or complete closure of fistulas in pts with fistulating disease. The following variables were evaluated in a univariable analysis: sex, age at diagnosis, smoking habit, site of disease, previous surgery, extraintestinal manifestations and concomitant therapies, type of fistulas. Side effects were evaluated. Results: (a) steroid dependant/resistant disease: 94 pts (24,5%) had a clinical response and 228 pts (59,5%) reached clinical remission. (b) fistulating disease: 80 pts (30,6%) had a reduction of 50% of the number of fistulas and in 107 pts (41%) a total closure of fistulas was observed. For luminal disease previous surgery predicted a worse response (OR 0.54, CI 0.296-0.975); for fistulating disease other fistulas responded less than perianal fistulas (0.57, CI 0.303-1,097). No serious side effects were observed. Conclusion: Infliximab is effective in steroid dependant/resistant patients and in fistulating disease. Previous surgery and other fistulas predicted a worse response in luminal and fistulating disease respectively.