Effectiveness of Tofacitinib in the Treatment of Ulcerative Colitis in Real-World Clinical Practice

Tofacitinib in the Treatment of UC

Therapeutic options for inflammatory bowel diseases (IBD) are rapidly expanding. Janus kinase inhibitor (JAKi) tofacitinib is the first small-molecule drug approved for the treatment of moderate to severe ulcerative colitis (UC). Compared to monoclonal antibodies targeting specific cytokines, JAKis target multiple signaling pathways and substances believed to modulate inflammation in UC, such as interleukins IL-6, IL-12, IL-15, IL-23, and interferon gamma (IFN-γ).

Data from Clinical Studies vs. Real-World Clinical Practice

The effectiveness of tofacitinib in the therapy of UC has been previously confirmed by standard randomized controlled clinical trials (RCTs). However, a retrospective analysis of conducted RCTs revealed that only 26% of UC patients from the 'real world' would be eligible for inclusion in a 'register' RCT. Common reasons for exclusion included the use of topical rectal therapy, situations where the patient had not yet been treated with immunomodulators, newly diagnosed disease, or the need for colectomy.

Results obtained from non-interventional clinical evaluations are often referred to as real-world evidence (RWE). Data from everyday clinical practice, such as electronic health records, patient registries, and surveys, are evaluated. By studying a UC patient population more representative of clinical practice, RWE can offer additional insights into predictors of effectiveness and treatment sequencing and reveal new safety information. However, while RWE data provide many valuable insights, it is also important to recognize their limitations, such as the risk of various types of bias.

Mega-analyses of RWE Studies

Two meta-analyses recently focused on observational studies with tofacitinib in UC therapy.

Lucaciu et al. analyzed 9 studies involving 830 patients. After 8 weeks (median), a clinical response was achieved in 51% of patients (95% confidence interval [CI] 41–60) and remission in 37% (95% CI 26–45). After 24 weeks, the clinical response was maintained in 40% of patients (95% CI 31–50) and remission in 29% (95% CI 23–36). 32% of patients experienced at least one adverse event, most commonly mild infection (13%) and worsening of UC requiring colectomy (13%). One-third of patients (35%) discontinued tofacitinib, most often due to a lack of primary response (51%).

In a more recent work, Taxonera et al. analyzed 17 studies with a total of 1162 UC patients. At week 8, a clinical response was observed in 62.1% of patients (95% CI 55.0–69.1) and remission in 34.7% (95% CI 24.4–45.1). At week 24, a response was observed in 50.8% of patients (95% CI 42.1–59.5) and remission in 38.3% (95% CI 29.2–47.5). Patients who had not previously been treated with biologics (11.6%) had a significantly higher response rate at week 8 (1.38; 95% CI 1.03–1.84; p = 0.032). The incidence of serious adverse events was 8.9 per 100 patient-years, and the incidence of herpes zoster was 6.9 per 100 patient-years. No significant cardiovascular events or thromboembolic complications were reported in any of the analyzed studies.

Conclusion

Meta-analyses of real-world studies confirm the effectiveness of tofacitinib in a highly refractory population of patients with moderate to severe active ulcerative colitis and an acceptable safety profile. Findings from real-world practice are also consistent with clinical trial results and further support the use of tofacitinib in UC.

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Sources:
1. Lucaciu L. A., Constantine-Cooke N., Plevris N. et al. Real-world experience with tofacitinib in ulcerative colitis: a systematic review and meta-analysis. Therap Adv Gastroenterol 2021 Dec 23; 14: 17562848211064004, doi: 10.1177/17562848211064004.
2. Taxonera C., Olivares D., Alba C. et al. Real-world effectiveness and safety of tofacitinib in patients with ulcerative colitis: systematic review with meta-analysis. Inflamm Bowel Dis 2022 Jan 5; 28 (1): 32–40, doi: 10.1093/ibd/izab011.