The safety and efficacy of ENTOCORT EC were evaluated in 994 patients with mild to moderate active Crohn’s disease of the ileum and/or ascending colon in 5 randomized and double-blind studies. The study patients ranged in age from 17 to 85 (mean 35), 40% were male and 97% were white. Of the 651 patients treated with ENTOCORT EC, 17 (2.6%) were ≥65 years of age and none were >74 years of age. The Crohn’s Disease Activity Index (CDAI) was the main clinical assessment used for determining efficacy in these 5 studies. The CDAI is a validated index based on subjective aspects rated by the patient (frequency of liquid or very soft stools, abdominal pain rating and general well-being) and objective observations (number of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal mass, body weight and hematocrit). Clinical improvement, defined as a CDAI score of ≤150 assessed after 8 weeks of treatment, was the primary efficacy variable in these 5 comparative efficacy studies of ENTOCORT EC capsules. Safety assessments in these studies included monitoring of adverse experiences. A checklist of potential symptoms of hypercorticism was used.

One study (Study 1) compared the safety and efficacy of ENTOCORT EC 9 mg qd in the morning to a comparator. At baseline, the median CDAI was 272. ENTOCORT EC 9 mg qd resulted in a significantly higher clinical improvement rate at Week 8 than the comparator (Table 1).

Two placebo-controlled clinical trials (Studies 2 and 3) were conducted. Study 2 involved 258 patients and tested the effects of graded doses of ENTOCORT EC (1.5 mg bid, 4.5 mg bid, or 7.5 mg bid) versus placebo. At baseline, the median CDAI was 290. The 3 mg per day dose level (data not shown) could not be differentiated from placebo. The 9 mg per day arm was statistically different from placebo (Table 1), while no additional benefit was seen when the daily ENTOCORT EC dose was increased to 15 mg per day (data not shown). In Study 3, the median CDAI at baseline was 263. Neither 9 mg qd nor 4.5 mg bid ENTOCORT EC dose levels was statistically different from placebo (Table 1).

Two clinical trials (Studies 4 and 5) compared ENTOCORT EC capsules with oral prednisolone (initial dose 40 mg per day). At baseline, the median CDAI was 277. Equal clinical improvement rates (60%) were seen in the ENTOCORT EC 9 mg qd and the prednisolone groups in Study 4. In Study 5, 13% fewer patients in the ENTOCORT EC group experience clinical improvement than in the prednisolone group (no statistical difference) (Table 1).

The proportion of patients with normal plasma cortisol values (≥150 nmol/L) was significantly higher in the ENTOCORT EC groups in both trials (60 to 66%) than in the prednisolone groups (26 to 28%) at Week 8.

The efficacy and safety of ENTOCORT EC for maintenance of clinical remission were evaluated in four double-blind, placebo-controlled, 12-month trials in which 380 patients were randomized and treated once daily with 3 mg or 6 mg ENTOCORT EC or placebo. Patients ranged in age from 18 to 73 (mean 37) years. Sixty percent of the patients were female and 99% were Caucasian. The mean CDAI at entry was 96. Among the four clinical trials, approximately 75% of the patients enrolled had exclusively ileal disease. Colonoscopy was not performed following treatment. ENTOCORT EC 6 mg/day prolonged the time to relapse, defined as an increase in CDAI of at least 60 units to a total score >150 or withdrawal due to disease deterioration. The median time to relapse in the pooled population of the 4 studies was 154 days for patients taking placebo, and 268 days for patients taking ENTOCORT EC 6 mg/day. ENTOCORT EC 6 mg/day reduced the proportion of patients with loss of symptom control relative to placebo in the pooled population for the 4 studies at 3 months (28% vs. 45% for placebo).