P949 Effectiveness and safety of rectal tacrolimus in patients with ulcerative colitis. TACRO-TOPIC study. A multicenter study from the young group of GETECCU
Authors: Fuentes-Valenzuela E , Bastón-Rey I , García-Alonso F J , Leo Carnerero E , Garcia de la Filia I , Pedraza Pérez A , Sáiz Chumillas R M , Pascual Oliver A , Muñoz Villafranca C , Moreno V , Suárez Ferrer C , Molina Arriero G , Ferreiro-Iglesias R , Vega Villaamil P , Gardeazábal Mateos D , Segarra-Ortega J X , Garrido Marín A , Doallo A I , Elosua A , Alonso-Galán H , Brunet- Mas E , Jimenez García N , López Romero-Salazar F , Velayos B , Carballo-Folgoso L , Pérez Santamaría C , Mata Román L , Núñez Ortiz A , Barrio J , Barreiro-de Acosta M , Gutiérrez-Casbas A 
Published: January 2024

Abstract

Background
Few small studies have assessed the efficacy of topical therapy with tacrolimus in patients with ulcerative colitis (UC). The aim of our study was to evaluate its effectiveness and safety in a real-world setting.

Methods
A multicenter observational retrospective study at 25 Spanish GETECCU hospitals was performed. Adult patients with UC who received topical tacrolimus from January 2009 to January 2023 were eligible. Inclusion criteria were proctitis, left-sided, or extensive colitis with persistent distal colonic activity confirmed endoscopically during the previous 3 months. Clinical and biochemical data were collected at baseline, week 4, 8 and 54. Tacrolimus trough levels were evaluated in week 4 and 8. Primary outcome was clinical response at week 8, defined as a ≥3 points or ≥30% decrease of partial Mayo score with ≥1point reduction in the bleeding score. Mean partial mayo scores were compared using the t-test. A p&lt;0.05 was considered statistically significant.

Results
106 patients, 59 (55.6%) males, median age 48.7 years (IQR:39.9-59.7), received rectal tacrolimus during a median of 9.7 weeks (IQR:5-18.7). Sixty-four patients (60.4%) received suppositories, 41 (38.7%) enemas and 1 patient an ointment (0.9%). Thirty (28.3%) were patients with proctitis, 45 (42.4%) with left colitis and 31 (29.2%) with extensive colitis. At baseline, 54 patients (50.9%) received concomitant biological/small molecules therapy, while 14 patients received immunomodulators. Most common dose was 2 mg (84%) Q24H (71.7%).
A significant decrease in mean partial mayo score was observed at week 4 and 8 (figure 1). Clinical response at week 8 was achieved in 63 patients (66.3%) and clinical remission in 42 (44.2%). 32 patients (33.7%) were non-responder at week 8. Clinical response and remission at week 4 were achieved in 56 (57.7%) and 33 (34.4%), respectively. Clinical response at week 8 was similar between the group with concomitant biological therapy and without (64.6.9% vs 68.1%, p=0.8). Clinical response at week 8 was similar among different extensions (proctitis: 55.6%; left colitis: 80%; extensive colitis 57.1%; p=0.052). Clinical outcomes are detailed in table 1.
Median tacrolimus trough levels at week 4 was 3.4 ng/ml (IQR 1.5-6.7) and 2.9 ng/ml (IQR 1.5-6) at week 8.
Adverse events were detected in 21 patients (19.8%), Thirteen were graded as mild and 8 moderate. Treatment was ceased due to adverse events in 11 (10.4%) patients.

Conclusion
Topical tacrolimus is effective in UC achieving clinical response in more than sixty percent at week 8 with even lower doses than reported in clinical trials. Adverse events reported in nearly 20% of patients were mostly mild.