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

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.