ge; 50% reduction in number of enterocutaneous fistulas draining upongentle compression on at least 2 consecutive visits without an increase in medication orsurgery for Crohn’s disease) was seen in 68% (21/31) of patients in the 5 mg/kg infliximabgroup (P = 0.002) and 56% (18/32) of patients in the 10 mg/kg infliximab group (P = 0.021)vs. 26% (8/31) of patients in the placebo arm. The median time to onset of response andmedian duration of response in infliximab-treated patients was 2 and 12 weeks, respectively.
Closure of all fistulas was achieved in 52% of infliximab-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 haveat least 1 draining enterocutaneous (perianal, abdominal) fistula. All patients received 5mg/kg infliximab at Weeks 0, 2 and 6. Patients were randomized to placebo or 5 mg/kginfliximab maintenance at Week 14. Patients received maintenance doses at Week 14 andthen every 8 weeks through Week 46. Patients who were in fistula response (fistula responsewas defined the same as in the first trial) at both Weeks 10 and 14 were randomizedseparately from those not in response. The primary endpoint was time from randomization toloss of response among those patients who were in fistula response.
Among the randomized patients (273 of the 296 initially enrolled), 87% had perianal fistulasand 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 toinfliximab maintenance had a longer time to loss of fistula response compared to the placebomaintenance group (Figure 2). At Week 54, 38% (33/87) of infliximab-treated patients had nodraining fistulas compared with 22% (20/90) of placebo-treated patients (P=0.02). Comparedto placebo maintenance, patients on infliximab maintenance had a trend toward fewerhospitalizations.
Figure 2 Life table estimates of the proportion of patients who had not lost fistularesponse through Week 54Patients who achieved a fistula response and subsequently lost response were eligible toreceive infliximab maintenance therapy at a dose that was 5 mg/kg higher than the dose towhich they were randomized. Of the placebo maintenance patients, 66% (25/38) responded to5 mg/kg infliximab, and 57% (12/21) of infliximab maintenance patients responded to 10
mg/kg.
Patients who had not achieved a response by Week 14 were unlikely to respond to additionaldoses of infliximab.
Similar proportions of patients in either group developed new fistulas (17% overall) andsimilar numbers developed abscesses (15% overall).
14.2 Pediatric Crohn’s Disease
The safety and efficacy of infliximab were assessed in a randomized, open-label study (StudyPeds Crohn’s) in 112 pediatric patients aged 6 to 17 years old with moderately to severelyactive Crohn’s disease and an inadequate response to conventional therapies. The median agewas 13 years and the median Pediatric Crohn’s Disease Activity Index (PCDAI) was 40 (on ascale of 0 to 100). All patients were required to be on a stable dose of 6-MP, AZA, or MTX;35% were also receiving corticosteroids at baseline.
All patients received induction dosing of 5 mg/kg infliximab at Weeks 0, 2, and 6. At Week10, 103 patients were randomized to a maintenance regimen of |
