Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial

Abstract

Background & aims: Thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARgamma), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis (UC).

Methods: This multicenter, randomized, double-blind, placebo-controlled clinical trial compared the efficacy of rosiglitazone (Avandia; GlaxoSmithKline, Philadelphia, PA) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC. Disease activity was measured with the Mayo score. The primary end point was clinical response (>/=2-point reduction) at week 12. Clinical remission (Mayo score </=2), endoscopic remission, and quality of life were secondary outcomes.

Results: After 12 weeks of therapy, 23 patients (44%) treated with rosiglitazone and 12 patients (23%) treated with placebo achieved clinical response (P = .04). Remission was achieved in 9 patients (17%) treated with rosiglitazone and 1 patient (2%) treated with placebo (P = .01). Endoscopic remission was uncommon in either treatment arm (8% rosiglitazone vs 2% placebo; P = .34). Clinical improvement was evident as early as 4 weeks after beginning treatment (P = .049). Quality of life was improved significantly at week 8 (P = .01), but not at week 4 (P = .48) or week 12 (P = .14). Serious adverse events were rare.

Conclusions: Rosiglitazone was efficacious in the treatment of mild to moderately active UC.

Trial registration: ClinicalTrials.gov NCT00065065.

Figure 1

Outcome of patients screened and enrolled in the trial.

Figure 2

a Proportion of patients achieving the primary and secondary outcomes at week 12. * p=.03; † p=.01 b Proportion of patients with improvement in the Partial Mayo Score (decrease by 2 points or greater from baseline). * p=0.049; † p=0.03; # p=0.06 c Proportion of patients with improvement in quality of life (IBDQ increase of 16 or more points) after 4, 8, and 12 weeks of therapy. ‡ p=0.04 d Proportion of patients with improvement in the individual components of the Mayo Score. Improvement was defined as a reduction of at least 1 point. Patients who withdrew from the study before week 12 were categorized as not having improvement. * p=0.04; † p=0.03; ‡ p=0.01.

Figure 2

a Proportion of patients achieving the primary and secondary outcomes at week 12. * p=.03; † p=.01 b Proportion of patients with improvement in the Partial Mayo Score (decrease by 2 points or greater from baseline). * p=0.049; † p=0.03; # p=0.06 c Proportion of patients with improvement in quality of life (IBDQ increase of 16 or more points) after 4, 8, and 12 weeks of therapy. ‡ p=0.04 d Proportion of patients with improvement in the individual components of the Mayo Score. Improvement was defined as a reduction of at least 1 point. Patients who withdrew from the study before week 12 were categorized as not having improvement. * p=0.04; † p=0.03; ‡ p=0.01.

Figure 2

a Proportion of patients achieving the primary and secondary outcomes at week 12. * p=.03; † p=.01 b Proportion of patients with improvement in the Partial Mayo Score (decrease by 2 points or greater from baseline). * p=0.049; † p=0.03; # p=0.06 c Proportion of patients with improvement in quality of life (IBDQ increase of 16 or more points) after 4, 8, and 12 weeks of therapy. ‡ p=0.04 d Proportion of patients with improvement in the individual components of the Mayo Score. Improvement was defined as a reduction of at least 1 point. Patients who withdrew from the study before week 12 were categorized as not having improvement. * p=0.04; † p=0.03; ‡ p=0.01.

Figure 2

a Proportion of patients achieving the primary and secondary outcomes at week 12. * p=.03; † p=.01 b Proportion of patients with improvement in the Partial Mayo Score (decrease by 2 points or greater from baseline). * p=0.049; † p=0.03; # p=0.06 c Proportion of patients with improvement in quality of life (IBDQ increase of 16 or more points) after 4, 8, and 12 weeks of therapy. ‡ p=0.04 d Proportion of patients with improvement in the individual components of the Mayo Score. Improvement was defined as a reduction of at least 1 point. Patients who withdrew from the study before week 12 were categorized as not having improvement. * p=0.04; † p=0.03; ‡ p=0.01.