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Fistulizing Crohn’s Disease The safety and efficacy of REMICADE were assessed in 2 randomized, double-blind, placebo-controlled studies in patients with fistulizing
Crohn’s disease with fistula(s) that were of at least 3 months' duration. Concurrent use of stable doses of corticosteroids, 5-aminosalicylates, antibiotics, MTX, 6-mercaptopurine (6-MP), and/or azathioprine (AZA) was permitted. In the first trial,10 94 patients received three doses of either placebo or REMICADE at weeks 0, 2, and 6. Fistula response (=50% reduction in number of enterocutaneous fistulas draining upon gentle compression on at least two consecutive visits without an increase in medication or surgery for Crohn’s disease) was seen in 68% (21/31) of patients in the 5 mg/kg REMICADE group (p=0.002) and 56% (18/32) of patients in the 10 mg/kg REMICADE group (p=0.021) vs. 26% (8/31) of patients in the placebo arm. The median time to onset of response and median duration of response in REMICADE-treated patients was 2 and 12 weeks, respectively. Closure of all fistulas was achieved in 52% of REMICADE-treated patients compared with 13% of placebo-treated patients (p<0.001). In the second trial (ACCENT II [Study Crohn’s II]), patients who were enrolled had to have at least one draining enterocutaneous (perianal,
abdominal) fistula. All patients received 5 mg/kg REMICADE at weeks 0, 2, and 6. Patients were randomized to placebo or 5 mg/kg REMICADE maintenance at week 14. Patients received maintenance doses at week 14 and then every eight weeks through week 46. Patients who were in fistula response (fistula response was defined the same as in the first trial) at both weeks 10 and 14 were randomized separately from those not in response. Text Continues Below
The primary endpoint was time from randomization to loss of response among those patients who were in fistula response. Among the randomized patients (273 of the 296 initially enrolled), 87% had perianal fistulas and 14% had abdominal fistulas. Eight percent also had rectovaginal fistulas. Greater than 90% of the patients had received previous immunosuppressive and antibiotic therapy. At week 14, 65% (177/273) of patients were in fistula response. Patients randomized to REMICADE maintenance had a longer time to loss of fistula response compared to the placebo maintenance group (Figure 2). At week 54, 38% (33/87) of REMICADE-treated patients had no draining fistulas compared with 22% (20/90) of placebo-treated patients (p=0.02). Compared to placebo maintenance, patients on REMICADE maintenance had a trend toward fewer hospitalizations. OVERDOSAGE Single doses up to 20 mg/kg have been administered without any direct toxic effect. In case of overdosage, it is recommended that the patient
be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately.
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