Introduction
Tofacitinib (TOFA) is an oral Janus kinase Inhibitor for the treatment of ulcerative colitis (UC). We aimed to prospectively assess the real-world effectiveness and safety of TOFA in patients with moderate-to-severe UC, using a stringent criteria for clinical benefit.
Aims & Methods
TOFAST study is a prospective, multicenter, observational study including patients initiating TOFA from 39 French centers (Dec 2020 – Jun 2023). This interim analysis reports one-year effectiveness and safety. The primary endpoint was clinical benefit at one-year, defined as PRO-2 remission [rectal bleeding subscore (RBS) of 0 and stool frequency subscore (SFS) of ≤1], regardless of TOFA discontinuation. Patients with colectomy, death, treatment with another biologic/JAKi/immunosuppressant or corticosteroids (CS) in the last 3 months were considered non-responders. Secondary endpoints included clinical remission, clinical response, change in daily PRO-2 scores during the first 14 days, the median time to relief, and safety. Clinical remission was defined as Partial Mayo Score (PMS) ≤2 with no subscore >1, clinical response as a decrease in PMS ≥ 3 points and ≥30% from inclusion with a concomitant decrease in RBS ≥ 1 point (absolute subscore of 0 or 1). Patient’s symptomatic relief was reported as the time in days from initiation of TOFA to improvement of their symptoms. Missing data were imputed as non-responders.
Results
150 and 146 patients were included in the safety and effectiveness analysis, respectively, with a median exposure duration of 7.4 [Q1; Q3: 2.9; 12.0] months. In the effectiveness population, mean (± SD) age was 36.9 ±13.6 years, median disease duration was 6.0 years [Q1; Q3: 2.6; 11.2], 47.2% of patients had pancolitis, and the mean total Mayo Score was 7.8 ±2.3. 94.5% of patients had previously received at least one TNF-inhibitor, 62.3% vedolizumab and 32.2% ustekinumab. 27.4% of patients received at least 3 biologics. All patients initiated TOFA at 10 mg b.i.d, in combination with 5-ASA and CS for 19.9% and 33.6% of patients, respectively.
At one-year clinical benefit was achieved by 38/146 (26.0%) patients, and 66/146 (45.2%) of patients were still treated with TOFA. 30.1% and 30.8% of patients achieved clinical remission and clinical response, respectively. For the 94 (64.4%) patients who reported symptomatic improvement the median time to relief was 7 days [Q1; Q3: 4.0; 14.0]. Among the 102 patients who completed their daily PRO-2 subscores during the first 14 days, 36 (35.3%) and 55 (53.9%) normalized their SFS and RBS, respectively by day 14.
89.3% of patients reported at least one adverse event (AE) and 23.3% reported at least one serious AE. Twenty-two (14.7%) infections, 3 cases of herpes zoster, 2 cases of cancers (one non-invasive low-grade urothelial carcinoma and one colon adenocarcinoma) as well as one death (considered not related to the treatment) were reported. No major cardiovascular or venous thromboembolic event were observed.
Conclusion
In this large prospective real-world cohort of refractory UC patients, one-year clinical benefit was achieved in 26% using a stringent PRO-2 endpoint. Nearly one third were in clinical remission. Rapid symptomatic relief within 14 days and a manageable safety profile reinforce the role of TOFA as a therapeutic option in difficult-to-treat UC.
Disclosure
This study has been sponsored by Pfizer. A Bouzidi and Y Brault are employees and shareholders of Pfizer.