For patients with moderate to severe ulcerative colitis (UC), tofacitinib appears safe and effective but is associated with a dose-dependent increase in adverse events, according to a meta-analysis published in the Journal of Clinical Gastroenterology.

Investigators searched Medline, Embase, Web of Science, and Cochrane Central for abstracts regarding the safety and efficacy of tofacitinib for patients with UC. Remission was the primary outcome and clinical response, steroid-free remission, and adverse events were all secondary outcomes.

Overall, 26 studies were included, 4 of which were randomized controlled trials and 22 were of observational design. Safety outcomes were reported in 25 studies and efficacy outcomes in 20. Remission rates were reported in 13 studies. At 8 weeks, 16 weeks, 6 months, and 1 year remission rates were, 29.81% (95% CI, 22.37%-37.25%; I2, 90%), 35.34% (95% CI, 30.28%-40.40%; I2, 33%), 32.27% (95% CI, 27.67%-36.88%; I2, 42%) and 38.03% (95% CI, 33.59%-42.48%; I2, 0%), respectively.


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Clinical response was evaluated in 18 studies. The percentage of patients achieving response at 8 weeks, 16 weeks, 6 months, and 1 year were, 59.41% (95% CI, 55.03%-63.94%; I2, 61%), 51.02% (95% CI, 42.65%-59.38%; I2, 75%), 48.24% (95% CI, 35.34%-61.14%) and 50.87% (95% CI, 42.16%-59.58%; I2, 67%), respectively. In 3 studies, the week 8 clinical response rates by history of biologic exposure were assessed and no statistical difference was reported. Comparing patients who were biologic-naïve with those who were biologic-experienced revealed that the odds of achieving clinical response for biologic-naïve patients was 1.59 (95% CI, 0.54-4.63).

Higher doses of tofacitinib were associated with an increased frequency of adverse events. The pooled incidence rate for several adverse events across all doses were: 4.41 per 100-patient years (PYs) (95% CI, 2.32-8.38 per 100-PY; I2, 78%) for serious infections, 0.91 per 100-PY (95% CI, 0.43-1.93 per 100-PY; I2, 37%) for major adverse cardiovascular events, and 0.91 per 100-PY (95% CI, 0.61-1.34 per 100-PY; I2, 0%) for nonmelanotic squamous cell malignancies.

Study limitations include potential bias that is inherent in observational studies, as well as heterogeneity across the included studies and in end-point definitions. Additionally, there was potential under-reporting of minor adverse events. Finally, most observational studies included reported only on short-term outcomes and had small sample sizes which may have contributed to low-quality evidence.

The researchers concluded, “Further long-term studies of tofacitinib use in UC are

needed to better define the maintenance of efficacy and to identify any late emerging safety signals.”

Reference

Taneja V, El-Dallal M, Haq Z, et al. Effectiveness and safety of tofacitinib for ulcerative colitis: Systematic review and meta-analysis. J Clin Gastroenterol. Published online September 9, 2021. doi: 10.1097/MCG.0000000000001608