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DOP022 Tacrolimus suppositories as induction therapy for refractory ulcerative proctitis: a randomised controlled trial

J.E. Kreijne1*, M.R. Lie1, G. Dijkstra2, M. Löwenberg3, G. van Assche4, R.L. West5, D. van Noord5, A.A. van der Meulen - de Jong6, B.E. Hansen1,7, A.C. de Vries1, C.J. van der Woude1

1Erasmus MC, Gastroenterology and Hepatology, Rotterdam, The Netherlands, 2University Medical Center Groningen and University of Groningen, Gastroenterology and Hepatology, Groningen, The Netherlands, 3Academic Medical Center Amsterdam, Gastroenterology and Hepatology, Amsterdam, The Netherlands, 4University Hospitals Leuven, KU Leuven, Gastroenterology, Leuven, Belgium, 5Franciscus Hospital and Vlietland Hospital, Gastroenterology and Hepatology, Rotterdam, The Netherlands, 6Leiden University Medical Center, Gastroenterology and Hepatology, Leiden, The Netherlands, 7Toronto General Hospital, Center for Liver Disease, Toronto, Canada


The treatment of 5-ASA refractory ulcerative proctitis (UP) remains challenging. Previous studies have shown that topical tacrolimus is effective for the treatment of refractory UP. However, the efficacy of tacrolimus as induction therapy compared with topical corticosteroids is unknown.


We conducted a multicentre double-blinded randomised controlled trial in7 hospitals (EUDRACT number: 2013-001259-11). We randomly allocated adult patients (patients) with refractory UP in a 1:1 ratio, using a sealed envelope method, to either tacrolimus 2 mg suppositories OD (TSP) or beclomethasone 3 mg suppositories OD (BSP). Primary outcome was combined clinical remission, defined as a Colitis Activity Index (CAI) ≤ 4 and endoscopic remission, defined as Mayo score of 0 after 4 weeks. Secondary outcomes included clinical response defined as a decrease of CAI ≥3 from baseline, endoscopic response defined as a decrease in Mayo score ≥1 and/or decrease ≥5 cm extend of inflammation, and safety. All analyses were intention to treat. Outcomes were compared using X2 test or Mann–Whitney U test as appropriate.


Between February 2014 and November 2017, 88 patients were included (66% F, mean age 41.8 years (SD14), median disease duration 7.1 years [IQR 2.8–13.6]). After randomisation, 45 patients received TSP and 43 patients BSP. Concomitant treatments in 53 patients (60%) were comparable for TSP and BSP patients; 5-ASA 17 vs. 23; immunomodulators 12 vs. 5; biologics 5 vs. 4, respectively (p > 0.05). Primary outcome was achieved in 6/45 (13.3%) patients receiving TSP vs. 6/43 (13.9%) patients who received BSP (p = 0.93). Clinical remission rate at week 4 was similar between the TSP group (53.3%, n = 24) and BSP group (58.1% n = 25) (p = 0.35). Endoscopic remission at week 4 was achieved in 24.4% (n = 11) patients treated with TSP vs. 13.9% (n = 6) patients treated with BSP (p = 0.11). The secondary outcome clinical response was achieved in 64.4% (n = 29) TSP patients and in 67.4% (n = 29) BSP patients (p = 0.46). Endoscopic response was seen in 55.6% (n = 25) TSP patients vs. 58.1% (n = 25) BSP patients (p = 0.47). Adverse events were reported in 22 (48.8%) TSP patients vs. 13 (30.2%) BSP patients (p = 0.05). Serious adverse events occurred in five patients (3 TSP, p = 0.68).


In patients with 5-ASA refractory UP efficacy of topical tacrolimus was not statistically different compared with beclomethasone for inducing combined clinical and endoscopic remission, despite the observation of a higher rate of endoscopic remission after topical TSP. No differences were observed in clinical and endoscopic response rates. Fewer adverse effects were observed in the BSP-treated patients. Overall, our results demonstrate that tacrolimus suppositories could be considered as an alternative induction strategy for refractory UP (ZonMw Grant 836011003).