DENVER—Dose de-escalation of tofacitinib appears to be safe and effective for patients with ulcerative colitis, but physicians should validate response to an initial induction dose before de-escalating therapy, according to data presented at the 2023 Crohn’s and Colitis Congress (abstract P038).

Findings from the retrospective analysis of 162 patients at the University of California, San Francisco (UCSF) showed that dose de-escalation of tofacitinib in patients with ulcerative colitis did not lead to a significant increase in flare-ups. After a median follow-up of 12 months, the cumulative incidence rates of ulcerative colitis flare at 12 months were similar in patients with and without dose de-escalation (56% vs. 58%; P=0.81).

The researchers also identified several factors associated with ulcerative colitis flare after dose de-escalation, including a shorter induction course (<16 weeks) and active disease at six months of tofacitinib (Xeljanz, Pfizer). Of note, most patients were able to recapture clinical response after dose re-escalation, the co-investigators reported.

“Based on these real-world data, providers should consider doing an endoscopic assessment at the eight- to-16-week mark to see if there’s improvement before deciding to dose de-escalate tofacitinib,” said lead researcher, Amy Yu, MD, a clinical fellow at UCSF.

Real-World Data on De-escalation
Dr. Yu and her co-investigators aimed to evaluate treatment outcomes after tofacitinib dose de-escalation in patients with ulcerative colitis in a real-world cohort. The researchers included adults with moderate to severe ulcerative colitis who were treated with tofacitinib at UCSF between January 2012 and January 2022.

Overall, 54% of patients were male, 71% were white, and the median age was 38 years. In addition, 41% of patients had moderate ulcerative colitis, while 51% had severe disease. The duration of induction treatment (10 mg twice daily) was eight, 16 or greater than 16 weeks. Dose de-escalation was defined as a decrease to 5 mg twice daily. 

The primary outcome measured was ulcerative colitis flare, defined as ulcerative colitis–related hospitalization or surgery, reinduction with tofacitinib dose increase, corticosteroid, or change of therapy class. The investigators explored predictors of ulcerative colitis flare using univariable and multivariable Cox regression. More than half of patients (52%) continued the induction dose, while 48% underwent dose de-escalation.

“Results of this real-world study showed that tofacitinib dose de-escalation is suitable for ulcerative colitis patients, with a cumulative incidence of ulcerative colitis flare at 12 months of 56% versus 58% for patients who did not de-escalate,” Dr. Yu said.  Patients without dose de-escalation had higher rates of ulcerative colitis–related hospitalization (27% vs. 14%; P=0.04) and change of therapy class (39% vs. 12%; P<0.01) compared with those who de-escalated.

According to Dr. Yu, these findings provide important insights for medical professionals on the use of tofacitinib for the treatment of ulcerative colitis and may guide decisions on optimal maintenance dose in real-world settings. In addition to endoscopic assessment at the eight- to-16-week mark before de-escalating therapy, Dr. Yu noted that a longer induction dosing should be considered in specific patients. “In patients who may be refractory or have severe disease, a longer dosing schedule could help balance the risk/benefit of the patient’s clinical symptoms, disease and the risk of adverse events associated with tofacitinib.”

—Chase Doyle