Authors
A. CREMER (1), T. LOBATON (2), S. VIEUJAN (3), P. BOSSUYT (4), J. RAHIER (5), F. BAERT (6), O. DEWIT (7), E. MACKEN (8), M. SOMERS (8), A. VIJVERMAN (9), P. VAN HOOTEGEM (10), F. MANA (11), B. WILLANDT (12), P. CAENEPEEL (13), E. HUMBLET (13), F. D'HEYGERE (14), A. VERRETH (15), A. EL NAWAR (16), J. COENEGRACHTS (17), S. DEWIT (18), S. DE CONINCK (19), N. SCHOOFS (20), S. DELEN (21), J. DUTRE (22), C. THIENPONT (23), S. VANDEN BRANDEN (24), D. STAESSEN (25), D. FRANCHIMONT (1) / [1] Erasme Hospital, Brussels, Belgium, Department of Gastroenterology, [2] Ghent University Hospital, Ghent, Belgium, Department of Gastroenterology, [3] CHU Sart Tilman, Liège, Belgium, Department of Gastroenterology, [4] Imelda Hospital, Bonheiden, Belgium, Department of Gastroenterology, [5] CHU UCL Namur, Yvoir, Belgium, Department of Gastroenterology, [6] AZ Delta, Roeselare, Belgium, Department of Gastroenterology, [7] Cliniques universitaires Saint-Luc, Brussels, Belgium, Department of Gastroenterology, [8] Antwerp University Hospital, Edegem, Belgium, Department of Gastroenterology, [9] CHR Citadelle, Liège, Belgium, Department of Gastroenterology, [10] Algemeen Ziekenhuis Sint-Lucas, , Belgium, Department of Gastroenterology, [11] Clinique Saint-Jean, Brussels, Belgium, Department of Gastroenterology, [12] AZ Sint-Jan Brugge-Oostende, Brugge, Belgium, Department of Gastroenterology, [13] Ziekenhuis Oost Limbug (ZOL), Genk, Belgium, Department of Gastroenterology, [14] AZ Groeninge, Kortrijk, Belgium, Department of Gastroenterology, [15] AZ Sint-Jozef, , Belgium, Department of Gastroenterology, [16] CENTRE HOSPITALIER MOUSCRON, Mouscron, Belgium, Department of Gastroenterology, [17] Jessa Ziekenhuis, Hasselt, , Belgium, Department of Gastroenterology, [18] Mariaziekenhuis Noord-Limburg, Overpelt, Belgium, Department of Gastroenterology, [19] Sint Andries ziekenhuis Tielt, Tielt, Belgium, Department of Gastroenterology, [20] Sint-Trudo ziekenhuis, Sint-Truiden, Sint-Truiden, Belgium, Department of Gastroenterology, [21] ZH Maas en Kempen, , Belgium, Department of Gastroenterology, [22] ZNA Jan Palfijn, Merksem, Belgium, Department of Gastroenterology, [23] ZNA Antwerpen, Antwerpen, Belgium, Department of Gastroenterology, [24] OnzeLieveVrouwziekenhuis, Aalst, , Belgium, Department of Gastroenterology, [25] GZA Sint-Vincentius ziekenhuis, Antwerpen, , Belgium, Department of Gastroenterology
Introduction
Tofacitinib, an oral small molecule Janus kinase inhibitor, has been approved in 2018 for the treatment of moderate to severe ulcerative colitis (UC) in Europe. We report on real-world short-term efficacy and safety data from a multicenter Belgium refractory cohort of UC patients with prior exposure to both anti-TNF and vedolizumab.
Aim
The aim of the study was to evaluate clinical and endoscopic response and remission rates at weeks 8 and 16.
Methods
This is an observational, national, retrospective multicenter study including all UC active patients started on tofacitinib (10 mg BID) from 25 centers in Belgium between November 2018 to August 2019. Prospectively collected data were retrospectively analyzed according intention-to-treat. Clinical response was defined as a decrease from baseline in Modified Clinical Mayo score (rectal bleeding, stool frequency) by ≥2 points, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Clinical remission was defined as a Modified Clinical Mayo score ≤1. Endoscopic response was defined as a decrease from baseline in Endoscopic Mayo score by ≥1. Endoscopic remission was defined as an Endoscopic Mayo score ≤1. Complete endoscopic remission was defined as an Endoscopic Mayo score of 0. Descriptive statistics and Wilcoxon signed rank test were calculated using Medcal 19.1.
Results
Median disease duration at baseline of the 70 included patients was 13 years (IQR 8-16). Nearly all patients were refractory to at least one anti-TNF and vedolizumab. 3 patients did not receive anti-TNF, and 2 did not receive vedolizumab. Modified Clinical Mayo score at baseline was 5 (IQR 3-5), and Endoscopic Mayo score was 3 (IQR 2-3). Fifty-four percent (38/70) of patients required prolonged induction at 10mg BID. Median follow-up was 16 weeks (IQR 13-26). Clinical evaluation was available in all patients at week 8 and 49 patients at week 16, while endoscopic data were available in 52 patients and 42 at weeks 8 and 16, respectively. Clinical response and remission were 63% and 41% at week 8 and 76% and 53% at week 16. Endoscopic response and remission were 44% and 23% at week 8 and 69% and 50% at week 16. Complete endoscopic remission was 13% at week 8 and 19% at week 16. Fifty percent (21/42) of the patients under steroids at baseline could have stopped steroids at week 16. Median baseline Modified Mayo score (rectal bleeding, stool frequency and endoscopy) decreased from 7 (IQR 5- 8) to 4 (IQR 2-7) after 8 weeks (n=49) (p<0.0001), and down to 2 (IQR 1-5) at week 16 (n=40) (p<0.0001). Median CRP significantly decreased from baseline (5.3 mg/l, IQR [1.9–16.8]) to 1 mg/l at week 8 (IQR 0.5-6.2) (n=49) (p=0.003). Tofacitinib was well tolerated with only 1 reported case of single dermatome herpes zoster and no case of venous thromboembolism.
Conclusions
Tofacitinib very effectively induced short-term clinical and endoscopic response and remission even in a refractory cohort of patients with UC in a real-world clinical setting. During this short-term follow-up, tofacitinib was well tolerated with respect to adverse events.
