ical response, defined as 50% reduction from baseline in the number of fistulae draining upon gentle compression on at least two consecutive visits (4 weeks apart), without an increase in the use of medicinal products or surgery for Crohn's disease.
Sixty-eight percent (21/31) of infliximab-treated patients receiving a 5 mg/kg dose regimen achieved a clinical response vs. 26% (8/31) placebo-treated patients (p = 0.002). The median time to onset of response in the infliximab-treated group was 2 weeks. The median duration of response was 12 weeks. Additionally, closure of all fistulae was achieved in 55% of infliximab-treated patients compared with 13% of placebo-treated patients (p = 0.001).
Maintenance treatment in fistulising active Crohn's disease
The efficacy of repeated infusions with infliximab in patients with fistulising Crohn's disease was studied in a 1-year clinical study (ACCENT II). A total of 306 patients received 3 doses of infliximab 5 mg/kg at week 0,2 and 6. At baseline, 87% of the patients had perianal fistulae, 14% had abdominal fistulae, 9% had rectovaginal fistulae. The median CDAI score was 180. At week 14, 282 patients were assessed for clinical response and randomised to receive either placebo or 5 mg/kg infliximab every 8 weeks through week 46.
Week-14 responders (195/282) were analyzed for the primary endpoint, which was time from randomisation to loss of response (see Table 7). Corticosteroid tapering was permitted after week 6.
Table 7: Effects on response rate, data from ACCENT II (Week-14 responders)
ACCENT II (Week-14 responders)
Placebo Maintenance
(n=99)
Infliximab Maintenance
(5 mg/kg)
(n=96)
p-value
Median time to loss of response through week 54
14 weeks
>40 weeks
< 0.001
Week 54
Fistula Response (%) a
23.5
46.2
0.001
Complete fistula response (%) b
19.4
36.3
0.009
a: A 50% reduction from baseline in the number of draining fistulas over a period of 4 weeks
b: Absence of any draining fistulas
Beginning at week 22, patients who initially responded to treatment and subsequently lost their response were eligible to cross over to active re-treatment every 8 weeks at a dose of infliximab 5 mg/kg higher than the dose to which they were originally randomised. Among patients in the infliximab 5 mg/kg group who crossed over because of loss of fistula response after week 22, 57% (12/21) responded to re-treatment with infliximab 10 mg/kg every 8 weeks.
There was no significant difference between placebo and infliximab for the proportion of patients with sustained closure of all fistulas through week 54, for symptoms such as proctalgia, abscesses and urinary tract infection or for number of newly developed fistulas during treatment.
Maintenance therapy with infliximab every 8 weeks significantly reduced disease-related hospitalisations and surgeries compared with placebo. Furthermore, a reduction in corticosteroid use and improvements in quality of life were observed.
Adult ulcerative colitis
The safety and efficacy of Remicade were assessed in two (ACT 1 and ACT 2) randomized, double-blind, placebo-controlled clinical studies in adult patients with moderately to severely active ulcerative colitis (Mayo score 6 to 12; Endoscopy subscore 2) with an inadequate response to conventional therapies [oral corticosteroids, aminosalicylates and/or immunomodulators |
