Randomised placebo-controlled trial of rituximab (anti-CD20) in active ulcerative colitis.

OBJECTIVE: To assess the safety and efficacy of the B lymphocyte (anti-CD20) antibody, rituximab, in the treatment of steroid-resistant moderately active ulcerative colitis (UC). METHODS: A double-blinded, randomised controlled trial with a 2:1 ratio of treatment:placebo (phase II) was carried out in the setting of a University teaching hospital. The subjects comprised 24 patients with moderately active UC who have either failed to respond to conventional corticosteroid therapy or who have relapsed during corticosteroid withdrawal. Five of 8 placebo-treated patients and 12 of 16 rituximab-treated patients were receiving azathioprine, 6-mercaptopurine or methotrexate. Two infusions of rituximab 1 g in 500 ml of 0.9% saline intravenously over 4 h (n=16) or saline placebo (n=8) were given at 0 and 2 weeks. Patients still receiving corticosteroids on entry (placebo group 7/8; rituximab group 14/16) continued a standard steroid tapering regimen. The primary end point was remission (Mayo score ≤ 2) at 4 weeks. Secondary end points included response (Mayo score reduced ≥ 3) at 4 and 12 weeks. RESULTS: Mayo score at entry was higher in rituximab-treated patients (mean 9.19; 95% CI 8.31 to 10.06) than for placebo patients (7.63; 6.63 to 8.62, p=0.03). At week 4 only 1/8 placebo-treated patients and 3/16 rituximab-treated patients were in remission (p=1.0), but 8/16 rituximab-treated patients had responded compared with 2/8 placebo-treated patients, with a median reduction in Mayo score of 2.5 (rituximab) compared with 0 (placebo; p=0.07). This response was only maintained to week 12 in 4/16. Mucosal healing was seen at week 4 in 5/16 rituximab-treated patients and 2/8 placebo-treated patients (non-significant). Rituximab was well tolerated, with one chest infection, three mild infusion reactions plus one case of (probably unrelated) non-fatal pulmonary embolism. CONCLUSIONS Rituximab has no significant effect on inducing remission in moderately active UC not responding to oral steroids. There was a possible short-term response that was not sustained. Rituximab is well tolerated in UC. CLINICAL TRIAL NUMBER: NCT00261118.

Effect of systemic corticosteroid therapy on risk for intra-abdominal or pelvic abscess in non-operated Crohn's disease.

BACKGROUND & AIMS: Systemic corticosteroid therapy increases risk of postoperative sepsis in Crohn's disease. This study investigates its effect on risk for sepsis in non-operated patients. METHODS: A retrospective case-control study was performed in 432 patients with Crohn's disease (the 94% of our database for whom adequate documentation could be retrieved). Two analyses were performed. The first tested the hypothesis that patients with perforating Crohn's disease (n = 86) were more likely to develop intra-abdominal or pelvic abscess (n = 29) if they had received systemic corticosteroids during the previous 3 months. The second analysis, confined to interventions since 1998, tested the hypothesis that corticosteroid therapy was more common during the 3 months before presentation with intra-abdominal or pelvic abscess (n = 12) than during the 3 months after presentation with a relapse of nonperforating disease (n = 24 consecutive patients). In both analyses adjustment was made for any other significant variable. RESULTS: Systemic corticosteroid therapy was associated with an adjusted odds ratio (OR) for intra-abdominal or pelvic abscess of 9.03 (95% confidence interval [CI], 2.40-33.98) in patients with perforating Crohn's disease. Patients receiving prednisolone > or = 20 mg per day had an OR of 2.81 (95% CI, 0.99-7.99) for abscess compared with those receiving a lower dose. In patients with relapsed active disease, corticosteroid therapy was associated with an unadjusted OR of 9.31 (95% CI, 1.03-83.91) for intra-abdominal or pelvic abscess. Neither smoking nor azathioprine usage was associated with increased risk for abscess. CONCLUSIONS: Systemic corticosteroid therapy for Crohn's disease is associated with increased risk for intra-abdominal or pelvic abscess.

Medical management of ulcerative colitis.

Patients with ulcerative colitis have no increased mortality compared to population controls and the disease can be cured be colectomy. This review concentrates on the medical management of ulcerative colitis including the management of active colitis, acute severe colitis and first presentation of colitis, maintenance of remission and long-term complications.

Medical management of Crohn's disease.

Current evidence strongly suggests that Crohn's disease is caused by an abnormal response to enteric flora. This review examines the current evidence for medical management of Crohn's disease, particularly focusing on alternative therapies to corticosteroids in managing disease relapses and preventing long-term complications.