maintenancegroup received 5 mg/kg at Weeks 2 and 6, and then 10 mg/kg every 8 weeks. Patients inresponse at Week 2 were randomized and analyzed separately from those not in response atWeek 2. Corticosteroid taper was permitted after Week 6.
At Week 2, 57% (311/545) of patients were in clinical response. At Week 30, a significantlygreater proportion of these patients in the 5 mg/kg and 10 mg/kg maintenance groupsachieved clinical remission compared to patients in the placebo maintenance group (Table 3).
Additionally, a significantly greater proportion of patients in the 5 mg/kg and 10 mg/kginfliximab maintenance groups were in clinical remission and were able to discontinuecorticosteroid use compared to patients in the placebo maintenance group at Week 54(Table 3).
Table 3 Clinical remission and steroid withdrawal
Single 5-mg/kg Dosea Three-Dose Inductionb
Placebo Maintenance Infliximab Maintenance q 8 wks
5 mg/kg 10 mg/kg
Week 30 25/102 41/104 48/105
Clinical remission 25% 39% 46%
P-valuec 0.022 0.001
Week 54 6/54 14/56 18/53
Patients in remission able to
discontinue corticosteroid used 11% 25% 34%
P-valuec 0.059 0.005 a Infliximab at Week 0
b Infliximab 5 mg/kg administered at Weeks 0, 2 and 6 c P-values represent pairwise comparisons to placebo
d Of those receiving corticosteroids at baseline
Patients in the infliximab maintenance groups (5 mg/kg and 10 mg/kg) had a longer time toloss of response than patients in the placebo maintenance group (Figure 1). At Weeks 30 and54, significant improvement from baseline was seen among the 5 mg/kg and 10 mg/kginfliximab-treated groups compared to the placebo group in the disease-specific inflammatorybowel disease questionnaire (IBDQ), particularly the bowel and systemic components, and inthe physical component summary score of the general health-related quality of lifequestionnaire SF-36.
Figure 1 Kaplan-Meier estimate of the proportion of patients who had not lost
response through Week 54
In a subset of 78 patients who had mucosal ulceration at baseline and who participated in anendoscopic substudy, 13 of 43 patients in the infliximab maintenance group had endoscopicevidence of mucosal healing compared to 1 of 28 patients in the placebo group at Week 10.
Of the infliximab-treated patients showing mucosal healing at Week 10, 9 of 12 patients alsoshowed mucosal healing at Week 54.
Patients who achieved a response and subsequently lost response were eligible to receiveinfliximab on an episodic basis at a dose that was 5 mg/kg higher than the dose to which theywere randomized. The majority of such patients responded to the higher dose.
Amongpatients who were not in response at Week 2, 59% (92/157) of infliximab maintenance patients responded by Week 14 compared to 51% (39/77) of placebo maintenance patients.
Among patients who did not respond by Week 14, additional therapy did not result in
significantly more responses [see Dosage and Administration (2)].
Fistulizing Crohn’s Disease
The safety and efficacy of infliximab were assessed in 2 randomized, double-blind, placebocontrolledstudies in patients with fistulizing Crohn’s disease with fistula(s) that were of atleast 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, 94 patients received 3 doses of either placebo or infliximab at Weeks 0, 2 and6. Fistula response (& |
