Crohns Colitis. 2021 Jul 5;15(7):1130-1141.doi: 10.1093/ecco-jcc/jjaa249.

Séverine Vermeire ¹, Chinyu Su ², Nervin Lawendy ², Taku Kobayashi ³, William J Sandborn ⁴, David T Rubin ⁵, Irene Modesto ⁶, Sean Gardiner ⁶, Nicole Kulisek ², Haiying Zhang ², Wenjin Wang ², Julian Panés ⁷

Author information

¹Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.

²Pfizer Inc, Collegeville, PA, USA.

³Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.

⁴Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.

⁵University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, IL, USA.

⁶Pfizer Inc, New York, NY, USA.

⁷Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.

Abstract

Background and aims: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present primary completion analysis from RIVETING, an ongoing, double-blind, randomised, parallel-group trial evaluating efficacy and safety of tofacitinib dose reduction to 5 mg twice daily [BID] versus remaining on 10 mg BID in patients in stable remission on tofacitinib 10 mg BID maintenance therapy.

Methods: Patients had received tofacitinib 10 mg BID for ≥ 2 consecutive years and been in stable remission for ≥ 6 months before enrolment. The primary endpoint was modified Mayo score remission at Month 6. Safety was assessed up to February 20, 2020 [data cut-off].

Results: In all, 140 patients were randomised [1:1] to tofacitinib 5 or 10 mg BID; 77.1% and 90.0% of patients in the 5 and 10 mg BID groups, respectively, were in modified Mayo score remission at Month 6 (adjusted difference 12.9%; 95% confidence interval [CI] 0.5-25.0). Smaller differences between treatment groups were seen in patients with baseline endoscopic subscore of 0 versus 1 [9.8%; -3.0-22.6, and 21.1%; -6.1-48.2, respectively], and in patients without versus with prior tumour necrosis factor inhibitor [TNFi] failure [9.5%; -6.6-25.6, and 17.4%; -1.6-36.3, respectively]. Adverse events [AE] and serious AE rates were similar across treatment groups; no deaths were reported.

Conclusions: Most patients in stable remission on 10 mg BID maintenance therapy maintained remission following dose de-escalation. For patients who dose de-escalated, those in deep endoscopic remission and those without prior TNFi failure were more likely to maintain remission. Efficacy data were limited to the first 6 months; a longer duration of follow-up during RIVETING will further characterise the impact of dose reduction on maintenance of remission. Safety findings were consistent with the established safety profile of tofacitinib.