CDP571, a humanised monoclonal antibody to tumour necrosis factor alpha, for moderate to severe Crohn's disease: a randomised, double blind, placebo controlled trial - PubMed (original) (raw)

Clinical Trial

CDP571, a humanised monoclonal antibody to tumour necrosis factor alpha, for moderate to severe Crohn's disease: a randomised, double blind, placebo controlled trial

W J Sandborn et al. Gut. 2004 Oct.

Abstract

Background: Targeting tumour necrosis factor alpha (TNF-alpha) has demonstrated efficacy in Crohn's disease.

Aim: To evaluate CDP571, a humanised antibody to TNF-alpha, for treating active Crohn's disease.

Patients: A total of 396 patients with moderate to severe Crohn's disease.

Methods: In a 28 week, randomised, double blind, placebo controlled trial, patients received intravenous CDP571 (10 mg/kg) or placebo every eight weeks to week 24. The primary outcome measure was clinical response (a decrease in the Crohn's disease activity index (CDAI) to > or =100 points or remission (CDAI score < or =150 points)) at week 28. A secondary outcome measure was clinical response (using the same definition) at week 2.

Results: Clinical response occurred at week 28 in 80/263 (30.4%) CDP571 patients and 31/132 (23.5%) placebo patients (p = 0.102). Clinical response at week 2 occurred in 90/263 (34.2%) CDP571 patients and 28/132 (21.2%) placebo patients (p = 0.011). Post hoc exploratory subgroup analysis of 159 patients with baseline C reactive protein (CRP) > or =10 mg/l demonstrated significant differences between CDP571 and placebo in clinical response rates at weeks 2 (CDP571, 50/101 (49.5%); placebo, 9/58 (15.5%); p<0.001) and 28 (CDP571, 29/101 (28.7%); placebo, 7/58 (12.1%); p = 0.018). Adverse events occurred at similar frequencies in both treatment groups.

Conclusions: CDP571 is modestly effective for short but not long term treatment of unselected patients with moderate to severe Crohn's disease. The clinical relevance of this short term effect is unclear. Post hoc analysis suggests both short and long term efficacy of CDP571 in patients with elevated baseline CRP (> or =10 mg/l). CDP571 is well tolerated.

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Figures

Figure 1

Figure 1

Trial profile. * Indicates that some patients withdrew from the trial for more than one reason. A total of 76 patients in the placebo group and 113 patients in the CDP571 trial withdrew prior to week 28.

Figure 2

Figure 2

Percentages of patients with Crohn’s disease at each study visit who experienced a clinical response (decrease in Crohn’s disease activity index (CDAI) score >100 points or who achieved clinical remission (CDAI score⩽150 points)) in the placebo and CDP571 groups (ITT population).

Figure 3

Figure 3

Mean scores or values at each study visit, according to treatment group. (A) Crohn’s disease activity index (CDAI) scores; (B) inflammatory bowel disease questionnaire (IBDQ) scores; and (C) C reactive protein (CRP) values (geometric means). Error bars represent SD values (A, B) or 95% confidence intervals (C).

Figure 4

Figure 4

Percentages of patients with Crohn’s disease at each study visit who experienced a clinical response (decrease in Crohn’s disease activity index (CDAI) score >100 points or who achieved clinical remission (CDAI score⩽150 points)) according to baseline C reactive protein (CRP) concentration. (A) Patients with a baseline CRP concentration ⩾10 mg/l; (B) patients with a baseline CRP <10 mg/l.

References

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