Retreatment and maintenance therapy with infliximab in fistulizing Crohn's disease.

OBJECTIVES: Infliximab has clearly demonstrated its efficacy in the short-term treatment of fistulizing Crohn's disease. We present here the results of retreatment and long-term maintenance therapy. PATIENTS AND METHODS: Eighty one consecutive patients with active fistulizing Crohn's disease, in whom previous treatments had failed, were treated with infliximab. All patients received as the initial treatment of 5 mg/kg i.v. infusions (weeks 0, 2, and 6). Those patients who failed to respond after the initial cycle (group 1, n = 25), or those who relapsed after having responded (group 2, n = 13), received retreatment with three similar doses (weeks 0,2, and 6). Those who responded to retreatment were included in a long-term maintenance programme (n = 44), with repeated doses (5 mg/kg i.v. infusions) every eight weeks for 1-2 years. RESULTS: In the initial treatment 56% of the patients responded partially; this response being complete in 44%. In the retreatment, 28% of group 1 (non-responders) presented a complete response, compared to 77% in group 2 (relapsers) (p < 0.0001). In the maintenance treatment, the global response was 88% (39/44). The mean number of doses per patient was 4.4 +/- 2 (range 1-9) with a duration of 36 +/- 12 weeks (range 8-72). Adverse effects were not significantly increased in either treatment. CONCLUSIONS: Both retreatment and long-term maintenance therapy with infliximab, are highly effective and well tolerated in fistulizing Crohn's disease patients.

Nimesulide-induced severe hemolytic anemia and acute liver failure leading to liver transplantation.

We present the case of a 63-year-old woman who had undergone 7 months of treatment with Nimesulide (100 mg/b.i.d.) for symptomatic osteoarthritis. The patient was admitted to our unit with a clinical picture of progressive jaundice over 3 weeks. Clinical and analytical studies revealed acute liver failure, this being confirmed by liver biopsy, which showed submassive necrosis. Serological tests for different viral agents causing hepatitis were all negative. In addition, she presented a picture of severe haemolytic anaemia resistant to several treatments and needed multiple transfusions. Twenty-three days after admission, the patient presented hepatic encephalopathy and received an orthotopic liver transplant on day 25. The evolution after transplantation was good and the patient continues in good health with no evidence of haemolysis almost 2 years later. Liver toxicity due to Nimesulide is well known, but to our knowledge the occurrence of haemolytic anaemia has not been related to this drug previously. For these reasons, Nimesulide has been restricted or removed from the market in several countries in recent months.

High serum tumor necrosis factor-alpha levels are associated with lack of response to infliximab in fistulizing Crohn's disease.

OBJECTIVES: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor-alpha (anti-TNF-alpha), has been effective in the treatment of patients with active Crohn's disease and with fistulas. We investigated the effect of infliximab on circulating cytokines and acute phase proteins in patients with fistulas to determine the clinical response to anti-TNF-alpha. METHODS: A total of 36 patients with fistulizing Crohn's disease were selected for study. Serum from patients was drawn before the infusion on day 0 and at wk 2, 4, 6, 8, and 10 after completion of treatment. Circulating concentrations of TNF-alpha, interleukin-1beta (IL-1beta), and IL-6 were measured by ELISA. The functional activity of circulating TNF-alpha was assessed by the WEHI 164 TNF-alpha bioassay. Acute phase proteins were also determined. RESULTS: Elevated TNF-alpha, IL-1beta, IL-6, and acute phase proteins were observed in patients with Crohn's disease. Of the patients with fistulas, 22 (61.1%) responded to treatment. Before receiving infliximab, higher levels of serum TNF-alpha were found in patients who did not respond to infliximab compared with those who did (median interquartile range 26, 0-245 pg/ml; n = 14 vs 0, 0-22 pg/ml, n = 22). Patients showed no change in circulating levels of TNF-alpha during the course of the study. CONCLUSIONS: This treatment produces a clinical improvement in about two-thirds of CD patients with fistulas. The circulating levels of TNF-alpha are associated with the response to infliximab and could help to identify patients who would benefit from anti-TNF-alpha treatment.