Tofacitinib effective in ulcerative colitis, but higher doses lead to adverse events

The overall efficacy and safety of tofacitinib in moderate-to-severe ulcerative colitis (UC) agree with clinical trial data, but a dose-dependent increase in adverse events (AEs) occurs, which underscores the importance of early dose de-escalation, according to a study.

Furthermore, the “[r]ate of clinical response after tofacitinib induction was similar in biologic-naïve and biologic-experienced patients,” the investigators said.

The databases of Medline, Embase, Web of Science, and Cochrane Central were searched for articles and abstracts reporting on the efficacy or safety of tofacitinib in UC. Remission was the primary outcome, while secondary ones included clinical response, steroid-free remission, and AEs. Twenty-six studies met the eligibility criteria.

Remission rates were 29.81 percent (95 percent confidence interval [CI], 22.37‒37.25; I², 90 percent) at week 8, 32.27 percent (95 percent CI, 27.67‒36.88; I², 42 percent) at 6 months, and 38.03 percent (95 percent CI, 33.59‒42.48; I², 0 percent) at 1 year.

Clinical response rates at week 8, 6 months, and 1 year were 59.41 percent (95 percent CI, 55.03‒63.94; I², 61 percent), 48.99 percent (95 percent CI, 36.92‒61.06; I², 91 percent), and 50.7 percent (95 percent CI, 42.16‒59.5; I², 67 percent), respectively.

Clinical response at week 8 in biologic-naïve patients, compared with biologic-experienced counterparts, had an odds ratio of 1.59 (95 percent CI, 0.54‒4.63).

Pooled incidence rates across all doses were 4.41 per 100 patient-years (PY; 95 percent CI, 2.32‒8.38; I², 78 percent) for serious infections, 0.91 per 100 PY (95 percent CI, 0.43‒1.93; I², 37 percent) for major adverse cardiovascular events, and 0.91 per 100 PY (95 percent CI, 0.61‒1.34; I², 0 percent) for nonmelanotic squamous cell malignancies.

Of note, a higher dose correlated with greater AE frequency.