Introduction

Tofacitinib, a selective inhibitor of Janus kinase, reduces mucosal  inflammation and immune cell activation in ulcerative colitis (UC). It has been proven to be effective in inducing and maintaining clinical response and remission in various real-world studies and meta-analyses. However, these studies have been limited by small sample sizes, shorter follow-up durations, or lack of representation from developing regions.

Aim

To evaluate real-life, long-term effectiveness and safety of tofacitinib in a large cohort of patients with refractory or difficult-to-treat UC

Patient Profile

• 127 patients with moderately to severely active UC (Mayo score of 6-12, with an endoscopic subscore of 2 or 3)

Method

Study Design

• Multicenter, retrospective, observational cohort study
• Patients received tofacitinib 10 mg twice daily for 8 weeks, followed by maintenance dose of 5 mg twice daily; dose optimization to 10 mg twice daily as a maintenance regimen was as per physician’s discretion
• In non-responders or partial responders to tofacitinib, continuation of induction dosage of 10 mg twice daily for a maximum of 16 weeks was as per physician’s discretion

Endpoints

• Efficacy endpoints: clinical remission and endoscopic response rates after one year, after induction (at weeks 12-16) and up to 26 weeks, clinical response after induction and at 26 weeks, steroid-free clinical remission after induction, at 26 weeks, and at one year, biochemical response after induction, at 26 weeks, and at one year, biochemical remission at 26 weeks and one year, and endoscopic remission within one year, primary and secondary loss of response, the need for dose optimization, UC-related hospitalization, the need for colectomy
• Safety endpoints: incidence of adverse events AEs and serious AEs (SAEs)

Results

Efficacy

• Tofacitinib achieved clinical remission in 31.5% of patients at weeks 12-16, 46.5% at 6 months, and 37% at 1 year (Figure 1)
• Similarly, it also demonstrated steroid-free clinical remission (28.6% at weeks 12-16, 44.8% at 6 months, and 37.1% of patients at 1 year)
• Clinical response was attained in 67.7% of the patients after tofacitinib induction (at weeks 12-16) and in 63% of patients at 6 months
• It achieved significant biochemical responses (51.7% after induction therapy and 50.9% at 6 months) and biochemical remission (33.6% at 6 months and 29.3% at 1 year)
• Tofacitinib led to endoscopic response in 46.0% and endoscopic remission in 15.3% of the patients
• The need for colectomy arose in 7.9% patients, and need for hospitalization in 10.2% patients on tofacitinib treatment and all these patients had been previously exposed to biologics
• An improvement or resolution of the extraintestinal manifestations (EIM) was achieved with tofacitinib treatment in 67.4% patients with active EIM
• A secondary loss of response to tofacitinib during follow-up occurred in 42.5% patients and hence required dose escalation to 10 mg twice a day
• Tofacitinib showed long-term effectiveness and tolerability (drug persistence rate was 73.3% at 12 months, 63.8% at 24 months and 54.3% at 36 months)
• It effectively facilitated to avoid or delay the need for colectomy (mean time to colectomy was 26.87 months) in UC patients; colectomy-free survival rate was 87.4% at 12 months, 78% at 24 months, and 68.5% at 36 months
• Clinical remission with tofacitinib at 1 year was significantly greater in bionaive patients vs. those who experienced biological failure (53.8% vs. 32.7%, p = 0.005)
• Tofacitinib treatment optimization was significantly more common in patients exposed to biologics than bionaive patients (46.5% vs. 26.9%, p = 0.048)

• The clinical remission rate after induction was significantly higher in patients with moderate disease versus those with severe disease (38.6% vs. 18.2%, p = 0.016).
• Significantly higher clinical response rates and the clinical remission rates were noted after induction therapy (66.7% vs. 27.3%, p = 0.032 & 23.8% vs. 0.0%, p = 0.03, resp.) and at 6 months (71.4% vs. 18.2%, p = 0.003 & 38.1% vs. 0.0%, p = 0.004, resp.) in patients with endoscopic Mayo scores 2 vs. those with Mayo scores 3
• Hypoalbuminemia at baseline was not associated with a higher discontinuation rate or loss of response to tofacitinib during follow-up
• The study showed that higher colectomy rate was linked to serum albumin levels <3.5 g/dL (21.4% vs. 4.1%, p = 0.013)

Figure 1: Effect of tofacitinib on the primary efficacy outcome

Safety 

• Tofacitinib was associated with AEs in 20.5% of patients (incidence rate, IR 8.19/100 patient-years) and SAEs in 13.4% patients (IR 5.35/100 patient-years)
• Most common SAEs were colectomy (IR 3.15/100 patient-years) and serious infections (IR 1.58/100 patient-years)

Conclusion

Tofacitinib effectively induced clinical and endoscopic remission and prevented colectomy for more than 2 years, with a favorable safety profile in this large, long-term real-world study in patients with biologically refractory UC

BMC Gastroenterol 2025; 25: 184