Lower Dose Tofacitinib Provides Remission for Ulcerative Colitis

Peter M. Irving, MD

A new analysis shows a dose reduction of tofacitinib still will likely achieve remission for patients with ulcerative colitis.

A team, led by Peter M. Irving, MD, IBD Unit, Guy's and St Thomas' Hospital, examined existing evidence on tofacitinib dosing strategies for patients with ulcerative colitis.

The Drug

Tofacitinib, an oral, small molecule, Janus kinase inhibitor (JAK) has been indicated for the treatment of patients with ulcerative colitis. The current induction dose is twice daily 10 mg tofacitinib, while the lowest effective dose is recommended for maintenance therapy. The treatment was first approved by the US Food and Drug Administration in 2018.

In the study, the investigators identified published evidence on dosing regiments, including expert interpretation of the data and how they could inform clinical practice.

Doses

The team assessed the use of tofacitinib 5 or 10 mg daily dosing using data from the tofacitinib UC clinical program in the context of different clinical scenarios, including experts’ opinions on the clinical implications of dose adjustments to inform the benefit/risk of using the different doses based on clinical scenarios and real-world data.

The data comes from 2 identical 8-week, phase 3 studies (OCTAVE Induction 1 and 2) where patients were randomized to receive either tofacitinib 10 mg twice daily, 15 mg twice daily discontinued following a protocol amendment or placebo for 8 weeks.

The investigators sought primary efficacy endpoints of remission at week 8 defined by a total Mayo score of at least 2, no individual subscore greater than 1, and a rectal bleeding subscore of 0.

The investigators considered disease severity, comorbidities, and previous biological exposure as factors to consider when adjusting a tofacitinib dose.

Results

Overall, they found endoscopic subscores can determine whether a patient is a suitable candidate for dose reduction. After a dose relapse, the response can be recaptured in a significant number of patients with a dose increase.

Data also shows real-world use of tofacitinib that is consistent with the data identified in clinical trials.

“Overall, the clinical data suggest that the majority of patients are able to maintain tofacitinib-induced remission on the lower dose, at least up to 52 weeks,” the authors wrote. “Due to the high risk of relapse for these patients (i.e. patients with prior biological failure), dose reduction may present a challenging clinical scenario. Conversely, patients without prior TNFi failure are more likely to maintain remission after dose reduction and may be less likely to require subsequent dose increase.”

The authors went on to say the results show there is a lot to consider when advising a patients with ulcerative colitis to change their dose of tofacitinib.

“Clinicians must consider the benefit/risk balance of tofacitinib 10 versus 5 mg (twice daily dosing) in terms of dose-related side effects, as well as the safety implications of undertreating active disease,” the authors wrote. “All patients should be closely monitored for disease relapse following dose reduction or interruption for early recapture of response.”

The study, “Review article: guide to tofacitinib dosing in patients with ulcerative colitis,” was published online in Alimentary Pharmacology & Therapeutics.