Intest Res.  2018 Apr;16(2):233-245. 10.5217/ir.2018.16.2.233.

Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies

• Motoya S
• Watanabe M
• Kim HJ
• Kim YH
• Han DS
• Yuasa H
• Tabira J
• Isogawa N
• Arai S
• Kawaguchi
• Hibi T

• KMID: 2417675
• DOI: http://doi.org/10.5217/ir.2018.16.2.233

Abstract

BACKGROUND/AIMS
Tofacitinib is an oral, small-molecule Janus kinase inhibitor being investigated for ulcerative colitis (UC). In OCTAVE Induction 1 and 2, patients with moderately to severely active UC received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks. Clinical responders in OCTAVE Induction were re-randomized to 52 weeks' therapy with placebo, tofacitinib 5 mg BID, or tofacitinib 10 mg BID.
METHODS
We conducted post-hoc efficacy and safety analyses of East Asian patients in OCTAVE Induction 1 and 2 and OCTAVE Sustain.
RESULTS
A total of 121 East Asian (Japan, Korea, and Taiwan) patients were randomized in OCTAVE Induction 1 and 2 (placebo, n=26; tofacitinib 10 mg BID, n=95), and 63 in OCTAVE Sustain (placebo, n=20; tofacitinib 5 mg BID, n=22; tofacitinib 10 mg BID, n=21). At week 8 of OCTAVE Induction 1 and 2, 18.9% of patients (18/95) achieved remission with tofacitinib 10 mg BID versus 3.8% (1/26) with placebo. In OCTAVE Sustain, the week 52 remission rates were 45.5% (10/22), 47.6% (10/21), and 15.0% (3/20) with 5 mg BID, 10 mg BID, and placebo, respectively. Adverse event rates were similar between groups in OCTAVE Induction and numerically higher with tofacitinib in OCTAVE Sustain. Serious adverse event rates were similar across groups in all studies. Infections were numerically more frequent with tofacitinib than placebo. Increases in serum lipid levels were observed with tofacitinib.
CONCLUSIONS
In East Asian patients with UC, tofacitinib demonstrated numerically greater efficacy versus placebo as induction and maintenance therapy, with a safety profile consistent with the global study population. ClinicalTrials.gov: NCT01465763; NCT01458951; NCT01458574.

Keyword

Janus kinase; Colitis, ulcerative; Clinical trials

MeSH Terms

Asian Continental Ancestry Group*
Colitis, Ulcerative*
Humans
Korea
Phosphotransferases
Ulcer*
Phosphotransferases

Figure

• 

  Fig. 1 Overview of the OCTAVE study design, including maintenance and open-label studies. Response in OCTAVE Induction 1 and 2 was defined as week 8 remission (total Mayo score ≤2, no individual subscore >1, and rectal bleeding subscore 0) or clinical response (decrease from baseline total Mayo score of ≥3 points and ≥30%, with an accompanying decrease in the rectal bleeding subscore of ≥1 or absolute rectal bleeding subscore ≤1). aFinal complete efficacy assessment at weeks 8 and 52; treatment continued to week 9 in OCTAVE Induction 1 and 2 and to week 53 in OCTAVE Sustain; bPatients in remission at open-label extension baseline received tofacitinib 5 mg BID; all other patients received tofacitinib 10 mg BID. BID, twice daily.

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  Fig. 2 Patient disposition of the East Asian population in (A) OCTAVE Induction 1 and 2 and (B) OCTAVE Sustain. Patients with insufficient clinical response included those who discontinued because of an adverse event (AE) of worsening UC. BID, twice daily.

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  Fig. 3 Proportion of East Asian patients in OCTAVE Induction 1 and 2 achieving (A) remission, (B) mucosal healing, (C) clinical response, (D) clinical remission, and (E) endoscopic remission at week 8 by treatment group, non-responder imputation. Remission: total Mayo score ≤2, no individual subscore >1, and rectal bleeding subscore 0; mucosal healing: Mayo endoscopic subscore 0 or 1; clinical response: decrease from baseline total Mayo score of ≥3 points and ≥30%, with an accompanying decrease in the rectal bleeding subscore of ≥1 or absolute rectal bleeding subscore ≤1; clinical remission: total Mayo score ≤2, no individual subscore >>1; endoscopic remission: Mayo endoscopic subscore 0. Data are from the full analysis set with non-responder imputation, central read. Δ, treatment effect size; BID, twice daily.

• 

  Fig. 4 Change from baseline in partial Mayo score over time in East Asian patients in (A) OCTAVE Induction 1 and 2 and (B) OCTAVE Sustain, by treatment group, observed case. Partial Mayo score: Mayo score excluding endoscopic findings subscore. Data are from the full analysis set, observed case based on descriptive statistics. BID, twice daily.

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  Fig. 5 Proportion of East Asian patients in OCTAVE Sustain achieving (A) remission, (B) mucosal healing, (C) sustained steroid-free remission among patients in remission at baseline, (D) clinical response, (E) clinical remission, and (F) endoscopic remission at week 52 by treatment group, non-responder imputation. Remission: total Mayo score ≤2, no individual subscore >1, and rectal bleeding subscore 0; mucosal healing: Mayo endoscopic subscore 0 or 1; sustained steroid-free remission: achieving remission at both weeks 24 and 52 and not requiring corticosteroids for ≥4 weeks before each visit; clinical response: decrease from the baseline total Mayo score of ≥3 points and ≥30%, with an accompanying decrease in the rectal bleeding subscore of ≥1 or absolute rectal bleeding subscore ≤1; clinical remission: total Mayo score ≤2, no individual subscore >1; endoscopic remission: Mayo endoscopic subscore 0. Data are from the full analysis set with non-responder imputation, central read. Δ, treatment effect size; BID, twice daily.

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