Extended Tofacitinib Induction Therapy Safely Elicits Clinical Responses in Ulcerative Colitis

UC colonoscopy
ulcerative colitis, biopsy, microscopic image, colonoscopy, IBD
Investigators tested the safety and efficacy of an additional 8-week course of tofacitinib monotherapy in patients with ulcerative colitis to determine whether a longer course of induction therapy would induce clinical responses.

Extended tofacitinib induction therapy was found to not only elicit clinical responses in patients with ulcerative colitis (UC) who did not respond to an initial 8-week course of the JAK inhibitor, but also endoscopic improvement and remission, according to study data published in Clinical Gastroenterology and Hepatology. Results from the phase 3 OCTAVE Open trial (ClinicalTrials.gov identifier: NCT01470612) showed that the safety profile of the 16-week extended induction course was similar to that of the 8-week standard induction course.

The investigators evaluated the 8-week extended induction course in a subset of 295 patients who previously received twice-daily tofacitinib (10 mg) in the OCTAVE Induction 1 (ClinicalTrials.gov identifier: NCT01465763) or OCTAVE Induction 2 (ClinicalTrials.gov identifier: NCT01458951) trials, did not have a clinical response at week 8, and subsequently enrolled in the open-label, long-term extension OCTAVE Open study. In OCTAVE Open, these patients received another 8-week course of twice-daily tofacitinib (10 mg), were assessed for response at month 2, and subsequently classified either as “delayed responders” or “complete non-responders” at the conclusion of the 16-week treatment period.

After the second 8-week course of tofacitinib therapy, patients deemed delayed responders received twice-daily maintenance tofacitinib (10 mg). Those who did not have a response after the extended induction course discontinued tofacitinib per protocol. Clinical response was defined as a decrease from induction study baseline total Mayo score of 3 or more points and 30% or greater, plus a decrease in rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.

Of the 295 patients included in the OCTAVE Open analysis, 148 were classified as delayed responders and 147, complete non-responders. After the additional 8 weeks of tofacitinib therapy in OCTAVE Open, 52.2% of the 295 patients achieved a clinical response. Most of these responders (55.8%) did not respond to prior tumor necrosis factor inhibitor-based therapy.

Among the delayed responders, 70.3% maintained a clinical response at 12 months of continued tofacitinib use, 44.6% were in remission, and 56.8% demonstrated endoscopic improvement. “Extended induction conferred a clinical response in approximately half of those patients who had not demonstrated a clinical response after an initial 8 weeks of tofacitinib therapy in OCTAVE Induction 1 or 2, and increased the total absolute clinical response rate to 74.6%,” the study authors said. “A considerable number of patients [56.1%] maintained a clinical response at month 36 of OCTAVE Open,” they added.

Importantly, the incidence of adverse events seen with the additional 8 weeks of tofacitinib therapy was comparable to that observed during the initial 8-week period (52.2% vs 55.4%). Serious adverse reactions were seen in 3.8% during the first 8 weeks and 3.7% during the second.

Safety was assessed up to month 2 in patients who did not respond to tofacitinib induction therapy in OCTAVE Open and up to May 2019 in patients who had a delayed response. Among the non-responders, 2 patients experienced serious infections and 1 patient had herpes zoster. In the delayed responder population, 1 patient had a pulmonary embolism after 216 days of treatment with tofacitinib; however, this patient had a history of deep vein thrombosis and pulmonary embolism. The safety analysis was limited by the “relatively short-term” patient exposure to tofacitinib and the “limited size” of the delayed responder subpopulation, according to the investigators.

The OCTAVE Open data indicate that the majority of patients with UC were able to achieve a clinical response after 16 weeks of tofacitinib therapy, validating the viability of this treatment strategy for this patient population. “The tofacitinib UC clinical program further supports the recommended dosing of tofacitinib 10 mg BID for induction (8 weeks) or extended induction (16 weeks)…However, patients who fail to achieve adequate therapeutic benefit from tofacitinib by week 16 should discontinue treatment,” the study authors concluded.

Disclosure: The clinical trials were supported by Pfizer. Multiple authors declared affiliations with industry. Please refer to the original article for a full list of the authors’ disclosures.

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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. Published online October 27, 2020. doi: 10.1016/j.cgh.2020.10.038.