Single-Center Experience With Upadacitinib 45-mg Reinduction for Ulcerative Colitis

Background:
For ulcerative colitis, the standard induction dosing for Upadacitinib (UPA) is 45 mg dosed daily for 8 weeks. Clinical trial data revealed that UC patients without response to initial 8 weeks of induction, who received an additional 8 weeks of 45 mg dosing, with subsequent clinical response, ultimately achieved clinical remission in 36% of cases at 52 weeks, without additional safety signals. Multiple patients in our center responded to UPA induction but developed recur-rent symptoms or had objective evidence of inflammation while on maintenance UPA dosing. Some of these patients were provided with additional 45 mg induction dose UPA for at least 8 weeks. We aim to describe our experience and outcomes with using additional UPA induction dosing courses.
Methods:
We retrospectively identified 8 patients within our IBD registry who received additional induction dosing of UPA 45 mg daily for 8 weeks or more. Clinical documentation, endoscopic Mayo score (EMS), and fecal calprotectin (FCP) were extracted prior to reinduction and after reinduction. Median follow up after initiation of reinduction course was 6 months.
Results:
Of the 8 patients, all had received at least 1 biologic prior to starting UPA, and 6 of 8 patients (75%) had previously received multiple biologics. All patients received, at minimum, an additional 8 weeks of UPA 45 mg daily, with reinduction occurring 18-295 days from finishing initial induction (median of 108.5 days). The reasons for reinduction were endoscopic inflammation (n=3, EMS 2-3), elevated FCP (n=3, FCP 1680-5050), or clinical symptoms (n=2). Post-reinduction objective outcomes were available for 7 or 8 patients. 2 of 7 patients (28.5%) achieved remission as assessed by objective means (EMS of 1 and FCP of 134), while 5 of 7 did not; 1 had an EMS of 3, 2 had an EMS of 2, and 2 with elevated FCP (354-930). Of the initial responders to reinduction, 1 has maintained a lower FCP of 181 at 30 weeks from reinduction, and 1 remains in clinical remission but is on long-term UPA 45 mg daily. Of the initial non-responders to reinduction, 2 proceeded to colectomy, 2 are on combination therapy with UPA and another advanced therapy, and 1 remains on UPA 30 mg daily for what is thought to be partial response (FCP 354 plus clinical remission).
Conclusions:
The objective response rate to UPA reinduction for patients with initial response to UPA induction, but recurrence of symptoms or inflammation after moving to maintenance dosing, was 27.5% (2/7), with an additional patient achieving partial response. One responder required long-term 45 mg induction dosing to maintain clinical remission. Overall, this suggests that it is rea-sonable to attempt reinduction courses in these patients, noting that this UC population is al-ready relatively medically refractory. Use of UPA reinduction as described above likely reflects a more generalizable, real-world approach for UC patients treated with UPA, and, within the limitations of the study, results in outcomes similar to an initial non-responder cohort treated with concurrent extended induction.