Current News from ECCO 2023: Tofacitinib in the Treatment of Ulcerative Colitis in Real-World Practice

Purpose of the Study

Tofacitinib is indicated for the treatment of rheumatoid, psoriatic, and juvenile idiopathic arthritis, ankylosing spondylitis, and ulcerative colitis. It belongs to targeted synthetic disease-modifying drugs, and its mechanism of action is Janus kinase (JAK) inhibition. For UC, the recommended dose is 10 mg twice daily during an 8-week induction and 5 mg twice daily in subsequent maintenance therapy. If there is no therapeutic benefit by the 8th week, the induction dose may be extended by another 8 weeks, followed by maintenance therapy.

The main goal of the cited study was to evaluate the sustained efficacy of tofacitinib in the treatment of UC.

Methodology and Course

This was a retrospective multicenter study involving patients with UC who received their first dose of tofacitinib at least 8 weeks before inclusion. They were monitored from this first dose until the treatment was discontinued or the last physician's check-up. Only patients with active disease, defined as a PMS (Partial Mayo Score) > 2 at the start of tofacitinib, were included in the efficacy analysis, and clinical efficacy was also assessed based on this score. For patients who discontinued tofacitinib before the last recorded check-up, missing data were supplemented using the last observation carried forward method, i.e., repeating the last recorded value.

Evaluated Patient Population

The study included 408 patients with an average age of 44 years, of which 40% were women. The median duration of UC was 7.5 years. 45% of these patients had comorbidities, 30% had cardiovascular risk factors, and 15% had a positive family history of idiopathic bowel diseases (IBD).

Regarding the extent of the disease, 57% of the included patients had extensive colitis, 37% had left-sided colitis, and 6% had proctitis. Extraintestinal manifestations were present in 28% of the patients. The median PMS at study entry was 6, severe clinical activity on endoscopic examination was found in 55% of patients, and 32% suffered from anemia. 92% of the patients had previously used biological therapy. Current mesalazine treatment was ongoing in 40%.

Results

Persistence of Treatment Efficacy

The incidence of tofacitinib discontinuation was 41% per patient-year of follow-up. The probability of continuing tofacitinib treatment was about 60% after 1 year and about 50% after 2 years. The main reasons for discontinuation were primary non-response to treatment (in 44%) and loss of response (in 26%). Younger age and moderate to severe clinical disease activity were associated with a higher probability of therapy discontinuation.

Achieving Remission

In terms of short-term efficacy, treatment response was achieved in 56% of patients after 4 weeks, including 38% of patients in remission; after 8 weeks, in 61% of patients, including 45% in remission; and after 16 weeks, these figures were 58% and 47%, respectively. Lower chances of achieving remission at week 8 were found in patients with moderate to severe disease activity at study entry compared to mild activity (odds ratio [OR] 0.2; 95% CI 0.1–0.4). The probability of maintaining the achieved remission decreased to 50% after about 18 months.

The dose of tofacitinib was increased in 66% of patients who experienced loss of response, and 82% of them showed improvement (with 60% achieving remission again). The proportion of participants in clinical remission after 6 months was 46%, after 12 months 44%, after 2 years 48%, and after 3 years 49%.

No evidence was found of an adverse impact of tofacitinib on extraintestinal manifestations of the disease or immune-mediated diseases.

Safety

The most common adverse events reported during tofacitinib treatment were infections (11%), of which 39% were serious and attributable to tofacitinib. In 20% of cases, these led to therapy discontinuation. Hypercholesterolemia was found in 6.6% of treated patients, but it was not severe in any case. Herpetic infections, including 2.6% of herpes zoster cases, occurred in 5.1%, with 10% being serious. Other adverse events that could be related to tofacitinib included anemia (3.7%), lymphopenia (1.7%), hypertriglyceridemia (1.2%), and thromboembolism (1%).

Conclusion

Tofacitinib is an effective drug for inducing remission even in patients with highly refractory UC. In this cohort, it led to remission in 45% of patients 8 weeks after the failure of previous biological therapy. A similar proportion of treated patients remained in remission after 1, 2, and 3 years of follow-up. Nevertheless, 44% of patients discontinue this treatment in real-world practice due to the absence of a primary response. However, dose escalation in cases of lost efficacy is likely to lead to remission re-achievement. This study did not reveal any new safety signals regarding the use of tofacitinib in UC patients.

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Source: Chaparro M., Acosta D., Rodríguez C. et al.; To-ReWard study group. P675 Real world evidence of tofacitinib in ulcerative colitis: short and long-term effectiveness, safety and impact of extraintestinal manifestations and immunomediated diseases. J Crohns Colitis 2023 Feb; 17 (Suppl. 1): i806–i808, doi: 10.1093/ecco-jcc/jjac190.0805.