Efficacy and safety of infliximab in patients with ulcerative colitis refractory to steroids and immunosuppressive agents

Introduction: Infliximab (IFX; Remicade, Schering Plough), a chimeric monoclonal antibody targeting TNF-α, represents the first biological approved for treatment of ulcerative colitis (UC). In order to evaluate the efficacy and safety of IFX in UC, we retrospectively analyzed the effect of IFX on induction and maintenance of remission, prevention of colectomy and safety in UC patients, refractory to steroids and immunosuppressive agents. Methods: All patients treated with immunosuppressive therapy with azathioprine or 6-mercaptopurine presenting with moderate to severe UC (Lichtiger score CAI 5–15) in our IBD center and treated with IFX for therapy-refractory UC for at least 2 months between January 2005 and May 2008 were retrospectively analyzed in this study. Following an induction therapy (week 0, 2, and 6), IFX infusions (5mg/kg) were performed every 8 weeks. For evaluation of disease activity the CAI was calculated for each patient at every visit. Clinical remission was defined as a score of 4 or less points, clinical response was defined as a decrease of at least 5 points or a decrease below 10 points calculated on two different days. Results: Overall, 72 patients were included into data analysis. Clinical response was observed in 46 patients (64%) with a decrease of median CAI from 11.5 (range 0–16) before IFX to 4 points (range 0–11) after first infusion (median decrease: 6, range 0–12). Twenty-one patients (29%) did not show significant clinical response to initial therapy (median Δ of CAI 2; range -5–4). In 5 cases (7%; 2 of initial responders and 3 non-responders), treatment was stopped due to infusion reaction. Analyzing the 46 responders during a median of 19 months (range 3–96), 27 (59%) were still in remission (median CAI 2; range 2–6) after 3 to 6 months. Eight patients (17%) with clinical response, but CAI >4, were maintained on scheduled IFX infusions every 8 weeks. Eight patients experienced loss of response, whereas 3 of them had to undergo surgery (colectomy n=2; ileostomy n=1). In one case, therapy was stopped after pregnancy was noticed, and in 2 patients follow-up was lost. Additionally to the infusion reactions in 7 patients, the following adverse events were observed: worsening of pre-existing depression (n=1), viral respiratory infection (n=3), arthralgia (n=2), vomiting (n=1). Conclusion: Patients with refractory UC benefit from IFX therapy. Larger cohorts and long term follow-up will be necessary to clarify the long term outcome regardomg efficacy and safety of IFX in UC.