DOP022 Tacrolimus suppositories as induction therapy for refractory ulcerative proctitis: a randomised controlled trial
Bibliographic record
Abstract
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).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.011 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".