REAL-WORLD EXPERIENCE WITH TOFACITINIB DOSE DE-ESCALATION IN PATIENTS WITH MODERATE AND SEVERE ULCERATIVE COLITIS

Abstract

Abstract BACKGROUND Tofacitinib is associated with sustained steroid-free remission and improved quality of life in patients with ulcerative colitis (UC), with the lowest effective dose recommended for maintenance therapy. However, there is limited real-world data to guide decision on optimal maintenance dose. We aimed to evaluate treatment outcomes of tofacitinib dose de-escalation in patients with UC in a real-world cohort. METHODS Included were adults with moderate-severe UC treated with tofacitinib between 1/2012-1/2022. Duration of treatment induction with 10 mg twice daily was 8, 16, or >16 weeks. Dose de-escalation was defined as decrease to 5 mg twice daily. Primary outcome was UC flare, defined as UC-related hospitalization/surgery, reinduction with tofacitinib dose increase, corticosteroid, or change of therapy class. Predictors of UC flare were explored using univariable and multivariable Cox regression. RESULTS Among 162 patients, 54% were male and 71% were white with a median age of 38 years, with 41% and 51% having moderate and severe UC, respectively. Eighty-three (52%) patients continued induction dose while 79 (48%) underwent dose de-escalation. There was no significant difference in number of prior biologic use or baseline endoscopic Mayo score, however, patients who underwent de-escalation were less likely to be steroid dependent during induction (50% vs 70%,p=0.01). After a median follow-up of 12 months, cumulative incidence rates of UC flare at 12 months were similar in patients with and without dose de-escalation (56% vs 58%,p=0.81), though patients without dose de-escalation had higher rates of UC-related hospitalization (27% vs 14%,p=0.04) and change of therapy class (39% vs 12%,p<0.01) compared to those who de-escalated. Among patients with dose de-escalation, cumulative rates of UC flare at 12 months were higher in patients with ongoing severe disease (Mayo 3) at 6 months of tofacitinib (Figure 1). In univariable Cox regression, prolonged duration of induction course with 10 mg twice daily >16 weeks was protective of UC flare (HR 0.37,95% CI 0.16-0.85) while ongoing severe disease (Mayo 3) was associated with UC flare (HR 6.41,95% CI 2.23-18.44), which remained significant after adjusting for age, sex, duration of induction course, and use of corticosteroid at dose de-escalation (HR 6.05, CI 2.00-18.35) (Table 1). Twenty-seven (29%) patients with UC flare had dose re-escalated to 10 mg twice daily with 63% recapturing clinical response at 12 months. CONCLUSIONS In this real-world cohort of UC patients with tofacitinib de-escalation, we observed a 56% cumulative incidence of UC flare at 12 months. Observed factors associated with UC flare after dose de-escalation included shorter induction course <16 weeks and active disease at 6 months of tofacitinib. The majority were able to recapture clinical response after dose re-escalation.