Effectiveness and Safety of Tofacitinib in the Management of Ulcerative Colitis: A Brazilian Observational Multicentric Study

Background:
Tofacitinib is an oral pan-JAK inhibitor approved for treatment of several immune-mediated inflammatory disorders, including ulcerative colitis (UC). We aimed to assess the real-life long-term effectiveness and safety data of tofacitinib in a large cohort of patients with refractory or difficult-to-treat UC.
Methods:
A multicenter retrospective observational cohort study, including patients with moderately to severely active UC who received tofacitinib for at least 8 weeks. Clinical remission and response, endoscopic response and remission, biochemical response and remission, steroid-free clinical remission, primary and secondary loss of response, drug discontinuation, and the need for dose optimization, need for colectomy and adverse events were evaluated for a long period of up to 30 months. Non-responder imputation analysis was used to evaluate all outcomes.
Results:
We included 127 patients with UC with an age of 40.3 ± 14.2 years, 58.2% males, 75.6% pancolitis, who had previously failed at least 1 biological therapy (79.5%), mainly anti-TNF (70.1%). Clinical remission was observed in 31.5% at week 12-16, 46.5% at 6 months, and 37.0% at 1 year. Steroid-free clinical remission was observed in 28.6%, 44.8%, and 37.1% at the same time periods, respectively. Biochemical remission at 6 months and at 1 year was achieved in 33.6% and 29.3% of the patients, respectively. Endoscopic response and endoscopic remission within of year were achieved in 46.0% and 15.3%, respectively. Ten patients (7.9%) required colectomy, and 13 patients (10.2%) needed hospitalization while on tofacitinib treatment, all of them were previously exposed to biologics. The colectomy rate was significantly higher in patients with serum albumin levels ≤ 3.5g/dL (21.4% vs 4.1%, p=0.013).
Conclusions:
In this a large, long-term real-world experience involving patients with mostly UC refractory to biologic therapy, tofacitinib has showed to be effective in inducing clinical remission and endoscopic improvement, as well as in preventing colectomy over 30 months with a good safety profile. Remarkably, baseline hypoalbuminemia was associated with higher rates of colectomy.