Tofacitinib Extended Induction May Improve Clinical Response Rate in Ulcerative Colitis

Extending tofacitinib induction therapy up to 16 weeks is a safe, efficacious option for patients with UC who do not respond to treatment by 8 weeks.

Extended tofacitinib dosing for up to 16 weeks of induction is associated with improved clinical response rates in patients with ulcerative colitis (UC) who failed to respond by 8 weeks, according to study results published in Clinical Gastroenterology and Hepatology.

The findings are based on the short- and long-term (up to 36 months) efficacy and safety profile of extended induction (up to 16 weeks) with tofacitinib 10 mg twice per day in patients who failed to achieve a clinical response to an initial 8 weeks of tofacitinib induction treatment.

The efficacy and safety of tofacitinib has been previously assessed in adults with moderately to severely active UC, including a dose-ranging phase 2 induction trial; a pair of phase 3 induction trials (OCTAVE induction 1 and 2); a phase 3 maintenance trial (OCTAVE sustain); and an ongoing, long-term extension trial (OCTAVE open).

The efficacy endpoints in OCTAVE open included clinical response (decrease from an induction study baseline total Mayo score of ≥3 points and ≥30%, as well as a decrease in rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of 0 or 1), endoscopic improvement, and remission. Safety endpoints included adverse events (AEs), serious AEs, and AEs of special interest.

Most patients who responded to extended induction maintained a clinical response up to 36 months. However, patients who fail to achieve adequate therapeutic benefit from tofacitinib by week 16 should discontinue treatment.

The OCTAVE open cohort included 523 patients (mean age, 42.7±13.9 years; women, 44%) who had a clinical response to 8 weeks of tofacitinib 10 mg twice per day in OCTAVE induction 1 and 2; 148 patients with delayed induction response,  (mean age, 40.4±13.5 years; women, 36.5%) who demonstrated a clinical response at month 2 of OCTAVE open; and 147 patients who were complete nonresponders (mean age, 37.4±13.2 years; women, 38.8%) and did not demonstrate a clinical response at month 2 of OCTAVE open.

After an additional 8 weeks of tofacitinib 10 mg twice per day in OCTAVE open, 52.2% (n=295) of the induction nonresponders achieved a clinical response. A total of 675 (n=905) patients achieved a clinical response with tofacitinib 10 mg twice per day after either 8 weeks of induction or the extended 16-week induction, for an overall clinical response rate of 74.6%.

Among patients with delayed response, 70.3%, 44.6%, and 56.8% (n=148 for all) maintained a clinical response, were in remission, and showed endoscopic improvement, respectively, at month 12 of OCTAVE open. The corresponding rates at month 24 were 58.8%, 43.2%, and 52.0%, respectively, and the rates at month 36 were 56.1%, 44.6%, and 52.0%, respectively.

The rate of any AE was 52.2% for tofacitinib induction nonresponders in OCTAVE open who received the additional 8 weeks of treatment compared with 55.4% in those who received an initial 8 weeks of treatment in OCTAVE induction and 56.4% in those who received placebo in OCTAVE induction. Among the tofacitinib induction nonresponders, 2 patients had serious infections and 1 had herpes zoster.

Study limitations in the safety analysis include the relatively short-term exposure to tofacitinib treatment in the tofacitinib UC clinical program and the limited size of the delayed responder subpopulation.

“The tofacitinib UC clinical program further supports the recommended dosing of tofacitinib 10 mg BID [twice per day] for induction (8 weeks) or extended induction (16 weeks),” the study authors concluded. “Most patients who responded to extended induction maintained a clinical response up to 36 months. However, patients who fail to achieve adequate therapeutic benefit from tofacitinib by week 16 should discontinue treatment.”

Disclosure: These trials were sponsored by Pfizer Inc. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References:

Sandborn WJ, Peyrin-Biroulet L, Quirk D, et al. Efficacy and safety of extended induction with tofacitinib for the treatment of ulcerative colitis. Clin Gastroenterol Hepatol. 2022;20(8):1821-1830.e3. doi:10.1016/j.cgh.2020.10.038