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.
ABSTRACT
BACKGROUND & AIMS: Endoscopic hemostasis is effective in treatment of bleeding peptic ulcers. However, rebleeding is difficult to treat and associated with substantial morbidity and mortality. We performed a prospective randomized trial to determine whether over-the-scope clips (OTSCs) are more effective than standard treatment of severe recurrent upper gastrointestinal bleeding. METHODS: We performed our study at 9 academic referral centers (in Germany, Switzerland, and Hong Kong) from March 2013 through September 2016. Adult patients with recurrent peptic ulcer bleeding following initially successful hemostasis (66 patients in the intent-to-treat analysis) were randomly assigned to groups (1:1) that underwent hemostasis with either OTSC or standard therapy. Standard therapy was defined as hemostasis with through-the-scope clips (TTSC, n = 31) or thermal therapy plus injection with diluted adrenaline (n = 2). The primary endpoint was further bleeding (a composite endpoint of a persistent bleeding despite endoscopic therapy according to the protocol or recurrent bleeding within 7 days after successful hemostasis). Patients with further bleeding were allowed to cross over to OTSC therapy. Main secondary endpoints were mortality, necessity of surgical or angiographic salvage therapy, duration of stay in the hospital or intensive care, number of blood units transfused, and complications associated with endoscopic therapy. RESULTS: Persistent bleeding after per-protocol hemostasis was observed in 14 patients (42.4%) in the standard therapy group and 2 patients (6.0%) in the OTSC group (P = .001). Recurrent bleeding within 7 days occurred in 5 patients (16.1%) in the standard therapy group vs 3 patients (9.1%) in the OTSC group (P = .468). Further bleeding occurred in 19 patients (57.6%) in the standard therapy group and in 5 patients (15.2%) in the OTSC group (absolute difference 42.4%; 95% confidence interval 21.6-63.2; P = .001) Within 30 days of follow-up, 1 patient in the standard therapy group (3.0%) and 1 patient in the OTSC group (3.0%) required surgical therapy (P = .999). Within 30 days of the procedure, 2 patients died in the standard therapy group (6.3%) and 4 patients died in the OTSC group (12.1%) (P = .672). There were no significant differences in the other secondary endpoints. CONCLUSIONS: In prospective randomized trial, we found endoscopic treatment with OTSCs to be superior to standard therapy with TTSCs for patients with recurrent peptic ulcer bleeding. STING Study, Clinicaltrials.gov no: NCT1836900.
