Intestinal Research

Naoki Isogawa

3 Articles

Inflammatory bowel diseases

Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn’s disease in Japanese and Korean patients: the OPERA study: Masayuki Saruta, Dong Il Park, Young-Ho Kim, Suk-Kyun Yang, Byung-Ik Jang, Jae Hee Cheon, Jong Pil Im, Takanori Kanai, Tatsuro Katsuno, Yoh Ishiguro, Makoto Nagaoka, Naoki Isogawa, Yinhua Li, Anindita Banerjee, Alaa Ahmad, Mina Hassan-Zahraee, Robert Clare, Kenneth J. Gorelick, Fabio Cataldi, Mamoru Watanabe, Toshifumi Hibi; Intest Res 2020;18(1):45-55. Published online January 30, 2020; DOI: https://doi.org/10.5217/ir.2019.00039

Background/Aims
PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn’s disease (CD).
Methods
OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein > 3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn’s Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients.
Results
In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating β7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment.
Conclusions
In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509)

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Novel Histone Deacetylase 6 Inhibitor Confers Anti-inflammatory Effects and Enhances Gut Barrier Function
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Downregulation of Heat Shock Protein 72 Contributes to Fibrostenosis in Crohn’s Disease
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Corrigendum: Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies: Satoshi Motoya, Mamoru Watanabe, Hyo Jong Kim, Young Ho Kim, Dong Soo Han, Hirotoshi Yuasa, Junichi Tabira, Naoki Isogawa, Shoko Arai, Isao Kawaguchi, Toshifumi Hibi; Intest Res 2018;16(3):499-501. Published online July 27, 2018; DOI: https://doi.org/10.5217/ir.2018.16.3.499

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Post-inflammatory Abdominal Pain in Patients with Inflammatory Bowel Disease During Remission: A Comprehensive Review
Kazuya Takahashi, Iman Geelani Khwaja, Jocelyn Rachel Schreyer, David Bulmer, Madusha Peiris, Shuji Terai, Qasim Aziz
Crohn's & Colitis 360.2021;[Epub] CrossRef
Two cases in which tofacitinib effectively treated both ulcerative colitis and alopecia areata
Oki Kikuchi, Daisuke Saito, Miki Miura, Haruka Wada, Ryo Ozaki, Sotaro Tokunaga, Shintaro Minowa, Masahiro Fukuyama, Tatsuya Mitsui, Akihito Sakuraba, Mari Hayashida, Jun Miyoshi, Minoru Matsuura, Manabu Ohyama, Tadakazu Hisamatsu
Clinical Journal of Gastroenterology.2020; 13(5): 788. CrossRef
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IBD

Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies: Satoshi Motoya, Mamoru Watanabe, Hyo Jong Kim, Young Ho Kim, Dong Soo Han, Hirotoshi Yuasa, Junichi Tabira, Naoki Isogawa, Shoko Arai, Isao Kawaguchi, Toshifumi Hibi; Intest Res 2018;16(2):233-245. Published online April 30, 2018; DOI: https://doi.org/10.5217/ir.2018.16.2.233

Abstract PDF Supplementary Material PubReader ePub

<b>Background/Aims</b><br/>

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.

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Journal of Pharmacy Practice.2021; 34(6): 913. CrossRef
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8,588 View
205 Download
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