Tofacitinib induction efficacy and safety in ulcerative colitis at week 8 - results from clinical practice
Abstract
Introduction: Tofacitinib is an oral Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). Its efficiency was proven in registration trials, however data from real clinical practice are still sparse.
Our aim was to evaluate efficacy and safety of tofacitinib in UC patients within 8-week induction period. Methods: Data from consecutive UC patients who started tofacitinib 10 mg twice a day were evaluated.
Disease activity was assessed by Mayo score including endoscopic Mayo at baseline and week 8 together with C-reactive protein (CRP) and fecal calprotectin (FC). At week 8, patients with total Mayo <=5 with endoscopic subscore <= 1 were considered responders.
Adverse events were registered at each visit. Results: A total of 24 patients (41.7% males), mean age 35.3 +- 11.8 years were included.
The mean disease duration was 8.3 +- 5.2 years. In median, the patients were previously treated with two biologic agents, however 25% of the patients were naïve to any biologic therapy.
Systemic corticosteroids were present in 41.7% of patients at baseline and no patient had concomitant biologic or immunosuppressive therapy. At week 8, 52.9% of patients responded to treatment.
The mean total Mayo decreased in responders from 5.9 +- 3.5 to 1.1 +- 1.3 (p = 0.01), while non-responders it changed from 8.0 +- 2.5 to 8.9 +- 2.1 (p = 0.86). Endoscopic subscore decreased from 2.0 +- 1.0 to 0.6 +- 0.7 (p = 0.02) in responders, however remained stable in non-responders (2.9).
CRP and FC dropped significantly in responders (6.7 +- 6.2 vs. 2.0 +- 2.2 mg/L, p = 0.04; 1,195 +- 1,189 vs. 578 +- 654 μg/g, p = 0.05), but not in non-responders. Non-responders had significantly higher baseline triglycerides compared to responders.
Tofacitinib was stopped in 23.5% of patients until week 8 due to insufficient response. Two patients reported headaches after treatment initiation and single events of Cytomegalovirus colitis, Clostridium difficile colitis and oral candidiasis occurred.
Conclusion: Tofacitinib was efficient in inducing clinical response with mucosal healing in about half of UC patients after 8 weeks of therapy. A need for long-term outcomes and for safety data with emphasis on infectious complications warrant further investigation.