Severe disease, short induction course up UC flare risk after tofacitinib dose de-escalation

Ulcerative colitis (UC) flare at 12 months has occurred in more than half of UC patients with tofacitinib dose de-escalation, according to a study presented at the recent Crohn’s & Colitis Congress (CCC 2023). Factors associated with UC flare following de-escalation are shorter induction course (<16 weeks) and active disease at 6 months of tofacitinib.

Majority of these patients have achieved clinical response after dose re-escalation, according to the researchers, led by Amy Yu from the University of California San Francisco, US.

“Tofacitinib is associated with sustained steroid-free remission and improved quality of life in patients with UC, with the lowest effective dose recommended for maintenance therapy,” said the researchers. “However, there is limited real-world data to guide decision on optimal maintenance dose.”

To address this, Yu and her team assessed treatment outcomes of dose de-escalation in 162 adults with moderate-to-severe UC (median age 38 years, 54 percent male, 71 percent White) treated with the tofacitinib between January 2012 and January 2022.

Patients were administered tofacitinib 10 mg twice daily for 8, 16, or >16 weeks. Dose de-escalation referred to a decrease to 5 mg twice daily. UC flare, the primary outcome, was defined as UC-related hospitalization or surgery, reinduction with tofacitinib dose increase, corticosteroid, or change of therapy class. Univariable and multivariable Cox regression were used to assess the UC flare predictors.

Of the included patients, 41 percent had moderate UC and 51 percent had severe UC. More than half of them (n=83, 52 percent) continued the induction dose, while the rest (n=79, 48 percent) underwent dose de-escalation. [CCC 2023, abstract P038]

No significant between-group difference was observed in the number of prior biologic use or baseline endoscopic Mayo score. However, patients in the de-escalation arm were less likely to be dependent on steroids during induction (50 percent vs 70 percent; p=0.01).

The cumulative incidence rates of UC flare after a median follow-up of 12 months were not significantly different between patients with and without dose de-escalation (56 percent vs 58 percent; p=0.81), but those who did not undergo dose de-escalation were more likely to be hospitalized for UC-related causes (27 percent vs 14 percent; p=0.04) and have a change of therapy class (39 percent vs 12 percent; p<0.01) relative to their de-escalated counterparts.

Among patients who underwent dose de-escalation, the cumulative rates of UC flare at 12 months were higher in those with ongoing severe disease (Mayo 3) at 6 months of tofacitinib treatment.

Univariable analysis revealed that prolonged duration of induction course (>16 weeks) with 10-mg tofacitinib twice daily was associated with a lower risk of UC flare (hazard ratio [HR], 0.37, 95 percent confidence interval [CI], 0.16‒0.85). In contrast, ongoing severe disease (Mayo 3) correlated with an increased risk (HR, 6.41, 95 percent CI, 2.23‒18.44), which persisted even after adjusting for age, sex, duration of induction course, and use of corticosteroid at dose de-escalation (HR, 6.05, 95 percent CI, 2.00‒18.35).

Finally, 27 patients (29 percent) with UC flare underwent dose re-escalation to 10 mg twice daily, and majority of them (63 percent) achieved clinical response at 12 months.