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P715 Real-world tofacitinib effectiveness and safety in patients with refractory ulcerative colitis

L. Lair-Mehiri*1, C. Stefanescu1, T. Vaysse2, D. Laharie3, X. Roblin4, I. Rosa5, X. Treton1, V. Abitbol6, A. Amiot7, G. Bouguen8, N. Dib9, M. Fumery10, B. Pariente11, F. Carbonnel2, L. Peryn-Biroulet12, M. Simon13, S. Viennot14, Y. Bouhnik1

1APHP-Hôpital Beaujon, Department of Gastroenterology, Clichy, France, 2APHP-Hôpital Bicêtre, Department of Gastroenterology, Le Kremlin Bicêtre, France, 3Bordeaux University Hospital, Department of Gastroenterology, Bordeaux, France, 4Saint-Etienne University Hospital, Department of Gastroenterology, Saint Etienne, France, 5Intercommunal Creteil Hospital Center, Department of Gastroenterology, Créteil, France, 6AP-HP, Cochin Hospital, Department of Gastroenterology, Paris, France, 7AP-HP, Hôpital Henri Mondor, Department of Gastroenterology, Créteil, France, 8Rennes University Hospital, Department of Gastroenterology, Rennes, France, 9Angers University Hospital, Department of Gastroenterology, Angers, France, 10Amiens University Hospital, Department of Gastroenterology, Amiens, France, 11Lille University Hospital, Department of Gastroenterology, Lille, France, 12Nancy University Hospital, Department of Gastroenterology, Nancy, France, 13Institut Mutualiste Montsouris, Department of Gastroenterology, Paris, France, 14Caen University Hospital, Department of Gastroenterology, Caen, France

Background

OCTAVE phase III trials confirmed the efficacy of tofacitinib, an oral Janus kinase inhibitor (JAK), over placebo for induction and maintenance of remission in patients with moderately to severely active ulcerative colitis (UC). Along this and before it was approved, tofacitinib was administered to a number of patients. Here, we further evaluated the real-world results of tofacitinib in patients with refractory UC (inadequate response, loss of response or intolerance to corticosteroids, immunosuppressant, antagonists to tumour necrosis factor (anti-TNF), vedolizumab or ustekinumab).

Methods

From December 2016 through August 2018, we conducted a multi-centre, retrospective study including all patients with active UC treated with tofacitinib induction therapy (10 mg twice daily) in France. The primary end point was survival without colectomy at Week 24. Secondary end points were survival without tofacitinib interruption and steroid-free clinical remission at Week 24. Disease activity was assessed using the partial Mayo Clinic score. Remission was defined by a total Mayo score ≤ 2 without any sub-score > 1, and the clinical response was defined by the decrease in the Mayo score ≥3 points and ≥30% compared with the inclusion and decrease in the rectal bleeding sub-score ≥1 or absolute sub-score ≤ 1. Survival analyses were performed using the Kaplan–Meier method.

Results

Among 37 patients treated with tofacitinib, 23 (62%) had pancolitis. All patients had been previously treated with TNF antagonist, 26 (70%) with two or more anti-TNFs and 36 (97%) with vedolizumab. Median total Mayo score at baseline was 9 (range 4–11). Median follow-up was 24 weeks (IQR). Non-parametric Kaplan–Meier estimator showed a survival without colectomy of 77% (n = 26) at Week 24 (CI 95%, 58.9%–87.8%); survival without treatment interruption was 62.6% (n = 25) at Week 24 (44.3%–76.4%) and 58.2% (n = 9) at Week 48 (39.2%–73.1%). Clinical response occurred in 15 (41%) patients including 12 (32%) who were in steroid-free clinical remission at Week 24. Adverse events occurred in 10 (27%) patients, of whom 5 (13.5%) were serious, corresponding to infections, and 3 (8.1%) adverse events were herpes zoster infections. No deaths were reported.

Conclusion

In this highly selected refractory population with moderate to severe UC, tofacitinib achieved steroid-free remission in one-third of patients at Week 24, and colectomy was avoided in more than 75% of cases at 6 months. Safety profile was consistent with those reported in the pivotal tofacitinib studies.