Background: The prevention of clinical relapse represents the major outcome in the treatment of ulcerative colitis (UC) patients. High fecal calprotectin levels indicate mucosal inflammation and have been shown to predict clinical relapse in many groups of UC patients. Epidemiological studies suggest that n-3 polyunsaturated fatty acids protect against the development of UC. Eicosapentaenoic acid, the major component of n-3 fish oil, has shown to have anti-inflammatory and chemopreventive properties. Aim of this study is to define the effectiveness of highly purified eicosapentaenoic acid as free-fatty acid (EPA-FFA) in reducing fecal calprotectin levels and preventing recurrence in a group of asymptomatic UC patients at risk of clinical relapse, defined as fecal calprotectin level ≥150 μg/g.
Methods: This is a double-blind, randomized, placebo-controlled study. Sixty UC patients with fecal calprotectin level ≥150 μg/g and Mayo endoscopic subscore ≤1, in stable therapy for at least the 3 previous months, were randomized 1:1 to receive either EPA-FFA (500 mg sustained-release capsules, 2 bid) or placebo (500 mg sustained-release capsules of capric and caprylic acids, 2 bid) for a 6 month period. Fecal calprotectin levels, clinical and laboratory assessments have been performed at baseline, 3 and 6 months or at the time of clinical relapse, which has been defined as the occurrence of symptoms accompanied by an increase in the partial Mayo score >2 and/or requiring a change in therapy. Patients who relapsed were referred for endoscopic evaluation.
Results: Cohort groups did not differ in clinical and demographic characteristics. Fecal calprotectin levels significantly decreased in the EPA-FFA group in comparison to the placebo group (p=0.004). At intention to treat analysis, 23.3% of patients in the EPA-FFA group and 50% of patients in the placebo group experienced a clinical relapse during the 6 months of follow up (χ2 p=0.03). At binary logistic regression analysis EPA-FFA treatment was the only factor affecting the number of patients who relapsed (HR 0.30, 95% CI 0.10–0.92, p=0.03). The cumulative 3 and 6 month relapse-free survival (RFS) was 86.7 and 76.7%, respectively, in the EPA-FFA group, compared to 80% and 50%, respectively, in the placebo group (Long-Rank test p=0.04) (Figure 1). Both treatments were safe and well tolerated, with no major side effects.
Conclusions: EPA-FFA decreases fecal calprotectin levels and is a safe and promising treatment to maintain symptom-free remission in UC patients.