Tacrolimus Suppositories in Therapy-Resistant Ulcerative Proctitis

Abstract

Background: Ulcerative proctitis may often be managed with topical salicylates or steroids alone, but in some patients, symptoms are persistent and severe. We analyzed the efficacy of tacrolimus suppositories in patients who had proven refractory to combined topical and systemic treatment.

Methods: In this retrospective analysis, ulcerative colitis activity index (CAI), side effects, co-medication and drug levels were assessed in 43 patients with distal ulcerative colitis who received suppositories containing 2 mg of tacrolimus b.i.d. as add-on medication.

Results: A total of 23 patients with ulcerative proctitis presented to follow-up within ≤50 days (mean 27.0 days) after suppositories were started. A decrease in CAI (from 8.0 to 5.5 points) was observed and 52.3% reached clinical remission (CAI ≤4). In total, 43 patients were available for analysis, of whom 9 had inflammation of the sigmoid colon as well. For the entire cohort, the median treatment duration was 76 days; 60% were in remission on the last documented visit. Serum measurements revealed a substantial tacrolimus level with a mean of 5.5 ng/mL. We observed one case of mild reversible acute kidney injury.

Conclusions: In ulcerative proctitis, adding tacrolimus suppositories can be an effective and safe option when topical mesalazine, corticoid formulations and concomitant oral or parenteral medications have failed.

Keywords: Inflammatory bowel disease; Tacrolimus; Therapy resistant; Topical treatment; Ulcerative proctitis.

Fig. 1.

a Duration from start of tacrolimus suppositories to last documented follow-up visit. The histogram with a bin width of 10 therapy days shows the distribution of treatment duration. b Colitis activity index at baseline and at last documented follow-up connected by lines. As the follow-up interval had a range from 7 to 2,157 days, we refrained from a statistical comparison.

Fig. 2.

a Colitis activity index response within 50 days, including all patients with distal ulcerative colitis (n = 31). The Wilcoxon matched-pairs signed-rank test was used to test for significant differences between the activity index at baseline and at a given follow-up time point. p values are two-tailed. The underlying jitter plot shows individual scores with corresponding endoscopic diagnosis. Thick horizontal bars are medians. ** p < 0.01. b Colitis activity index response within 50 days, including only patients with ulcerative proctitis (n = 23). The Wilcoxon matched-pairs signed-rank test was used to test for significant differences between the activity index at baseline and at a given follow-up time point. p values are two-tailed. The underlying jitter plot shows individual scores with corresponding endoscopic diagnosis. Thick horizontal bars are medians. *** p < 0.001.

Fig. 3.

a Tacrolimus blood level and time interval from last dose to blood sampling. All 82 available measurement pairs are shown. The fitted regression line and 95% confidence interval (shaded area) visualize the degree of correlation of blood levels with the length of the time interval. Spearman's ρ = −0.36, p < 0.001. b Correlation of tacrolimus blood level and colitis activity index in patients with proctitis only who presented to follow-up within 50 days (compare Fig. 2b). All available measurement pairs are shown. The fitted regression line and 95% confidence interval (shaded area) visualize the degree of correlation of blood levels with the length of the time interval. Spearman's ρ = −0.26, p = nonsignificant.