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OC-006 Randomised placebo-controlled trial of rituximab (anti-CD20) in active ulcerative colitis
  1. K Leiper,
  2. K Martin,
  3. A Ellis,
  4. S Subramanian,
  5. A Watson,
  6. S Christmas,
  7. D Howarth,
  8. F Campbell,
  9. J M Rhodes
  1. School of Clinical Science, University of Liverpool, Liverpool, UK

Abstract

Introduction Ulcerative colitis (UC) is associated with circulating auto-antibodies including pANCA. Although these are often seen as epiphenomena, they might be involved in pathogenesis. Suppression of the humoral response by use of anti-B lymphocyte antibodies might then be therapeutic. Prompted by the efficacy of the B cell (anti-CD20) antibody, rituximab, in rheumatoid arthritis we have conducted a phase II double-blinded placebo-controlled study of this antibody in UC (NCT00261118).

Methods 24 patients with active UC (Mayo score 6–12, but excluding severe colitis as defined by Truelove and Witts) who had either failed to respond to 2 weeks systemic corticosteroids or who had relapsed during steroid tapering were randomised to receive rituximab 1 g in 500 ml 0.9% saline intravenously over 4 h at 0 and 2 weeks (n=16) or saline placebo (n=8). Patients still receiving corticosteroids on entry (placebo group 7/8; rituximab group 14/16) continued a standard tapering regimen. Primary endpoint was remission (Mayo score <2) at 4 weeks. Secondary endpoints included response (reduction in Mayo score by >3 points) at 4 weeks and 12 weeks. The study was designed to assess safety but was powered to give 80% chance of excluding an 80% remission rate with active treatment compared with an estimated 25% placebo rate. Patients were randomised in blocks of five and analysis was by χ2, Student t or Mann–Whitney U, where appropriate.

Results Mayo score on entry was significantly higher in rituximab-treated patients (mean 9.19, 95% CI 8.31 to 10.06) than for placebo patients (7.63, 95% CI 6.63 to 8.62, p=0.03). Five of eight placebo patients and 12 of 16 rituximab patients were receiving Azathioprine, 6-mercaptopurine or methotrexate (n=1). At week 4 only 1/8 placebo-treated patients and 3/16 rituximab patients were in remission. However at week 4, 8/16 rituximab-treated patients had shown a response compared with 2/8 placebo with a median reduction in Mayo score of 2.5 (rituximab) compared with 0 (placebo, p=0.07). This response was however only maintained out to week 12 in 4/16. By week 12, UC had flared in 11/16 Rituximab patients and 7/8 placebo patients. Mucosal healing was seen at week 4 in 5/16 rituximab-treated patients and 2/8 placebo (NS). Rituximab was well tolerated with one chest infection, three mild infusion reactions plus one case of (probably unrelated) non-fatal pulmonary embolism.

Conclusion Rituximab is well tolerated by patients with ulcerative colitis and may have some therapeutic effect. Larger studies, probably using a different dosing regimen, will be needed to assess this.

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