enced a clinical response, defined as a decrease in CDAI by 70 points from baseline at the 4-week eva luation and without an increase in the use of medicinal products or surgery for Crohn's disease. Patients who responded at week 4 were followed to week 12. Secondary endpoints included the proportion of patients in clinical remission at week 4 (CDAI < 150) and clinical response over time.
At week 4, following administration of a single dose, 22/27 (81%) of infliximab-treated patients receiving a 5 mg/kg dose achieved a clinical response vs. 4/25 (16%) of the placebo-treated patients (p < 0.001). Also at week 4, 13/27 (48%) of infliximab-treated patients achieved a clinical remission (CDAI < 150) vs. 1/25 (4%) of placebo-treated patients. A response was observed within 2 weeks, with a maximum response at 4 weeks. At the last observation at 12 weeks, 13/27 (48%) of infliximab-treated patients were still responding.
Maintenance treatment in moderately to severely active Crohn's disease in adults
The efficacy of repeated infusions with infliximab was studied in a 1-year clinical study (ACCENT I).
A total of 573 patients with moderately to severely active Crohn's disease (CDAI 220 400) received a single infusion of 5 mg/kg at week 0. 178 of the 580 enrolled patients (30.7%) were defined as having severe disease (CDAI score > 300 and concomitant corticosteroid and/or immunosuppressants) corresponding to the population defined in the indication (see section 4.1). At week 2, all patients were assessed for clinical response and randomised to one of 3 treatment groups; a placebo maintenance group, 5 mg/kg maintenance group and 10 mg/kg maintenance group. All 3 groups received repeated infusions at week 2, 6 and every 8 weeks thereafter.
Of the 573 patients randomised, 335 (58%) achieved clinical response by week 2. These patients were classified as Week-2 responders and were included in the primary analysis (see Table 5). Among patients classified as non-responders at week 2, 32% (26/81) in the placebo maintenance group and 42% (68/163) in the infliximab group achieved clinical response by week 6. There was no difference between groups in the number of late responders thereafter.
The co-primary endpoints were the proportion of patients in clinical remission (CDAI<150) at week 30 and time to loss of response through week 54. Corticosteroid tapering was permitted after week 6.
Table 5: Effects on response and remission rate, data from ACCENT I (Week-2 responders)
ACCENT I (Week-2 responders)
% of Patients
Placebo Maintenance
(n=110)
Infliximab Maintenance
5 mg/kg
(n=113)
(p value)
Infliximab Maintenance
10 mg/kg
(n=112)
(p value)
Median time to loss of response through week 54
19 weeks
38 weeks
(0.002)
>54 weeks
(<0.001)
Week 30
Clinical Responsea
27.3
51.3
(<0.001)
59.1
(<0.001)
Clinical Remission
20.9
38.9
(0.003)
45.5
(<0.001)
Steroid-Free Remission
10.7 (6/56)
31.0 (18/58)
(0.008)
36.8 (21/57)
(0.001)
Week 54
Clinical Responsea
15.5
38.1
(<0.001)
47.7
(<0.001)
Clinical Remission
13.6
28.3
(0.007)
38.4
(<0.001)
Sustained Steroid-Free Remissionb
5.7 (3/53)
17.9 (10/56)
(0.075)
28.6 (16/56)
(0. |
