Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun;5(2):78-83.
doi: 10.1159/000506337. Epub 2020 Mar 6.

Management of Primary Nonresponders and Partial Responders to Tumor Necrosis Factor-α Inhibitor Induction Therapy among Patients with Crohn's Disease

Hideki Iijima  1 , Taku Kobayashi  2 , Mitsuo Nagasaka  3 , Shinichiro Shinzaki  1 , Kazuya Kitamura  4 , Yasuo Suzuki  5 , Mamoru Watanabe  6 , Toshifumi Hibi  2
Affiliations

Management of Primary Nonresponders and Partial Responders to Tumor Necrosis Factor-α Inhibitor Induction Therapy among Patients with Crohn's Disease

Hideki Iijima et al. Inflamm Intest Dis. 2020 Jun.

Abstract

Induction therapy with tumor necrosis factor-α (TNF-α) inhibitors is highly effective for the treatment of Crohn's disease. However, there are primary nonresponders (PNR) of TNF-α inhibitors without clinical response during the induction period. In addition, there are partial responders (PR), who show some efficacy, but clinical remission is not achieved by induction therapy. To date, the definition and clinical management of PNR and PR have not been established. This report summarizes the opinions of 36 Japanese experts attending the Japan Round Table Discussion on IBD Meeting regarding how to determine PNR and PR of TNF-α inhibitors and how to manage these patients in clinical practice. PNR, who do not show any initial improvement of clinical symptoms and serum C-reactive protein (CRP) levels, require re-assessment of intestinal complications. PR can be determined either by clinical symptoms, serum CRP levels, or imaging results. PR need intensification of the treatment with TNF-α inhibitors either with or without optimization of immunomodulators. Optimization of initial TNF-α inhibitor therapy may improve long-term outcomes, but more evidence is required to improve the use of TNF-α inhibitors for the prevention and management of PNR and PR.

Keywords: Crohn's disease; Expert opinion; Infliximab; Partial responder; Primary nonresponder.

PubMed Disclaimer

Conflict of interest statement

H.I. received lecture fees from Mitsubishi Tanabe Pharma, AbbVie, Janssen, EA Pharma, and Eisai and research grants from AbbVie and Nippon Kayaku. T.K. received consultancy fees from AbbVie GK, Alfresa Pharma, Covidien, Eli Lilly, Ferring Pharmaceuticals, Janssen, Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda Pharmaceutical, and Thermo Scientific, lecture fees from AbbVie GK, Ajinomoto Pharma, Asahi Kasei Medical, Astellas, Alfresa Pharma, Celltrion, EA Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Nippon Kayaku, Mochida Pharmaceutical, Takeda Pharmaceutical, Mi­tsubishi Tanabe Pharma, ZERIA, Eisai Co., Ltd., Gilead Sciences, Janssen, and JIMRO Co., Ltd., and research funding from AbbVie GK, EA Pharma Co., Ltd., Otsuka Holdings Co., Ltd., ZERIA, ­Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical, EA Pharma Co., Ltd., Thermo Fisher Scientific, Alfresa Pharma, Nippon Kayaku, and Asahi Kasei Medical. K.K. received lecture fees from Mitsubishi Tanabe Pharma, AbbVie, Janssen, and Takeda Pharmaceutical Co. and a research grant from AbbVie. S.S. received lecture fees from Mitsubishi Tanabe Pharma, AbbVie, Janssen, EA Pharma, and Eisai. Y.S. received lecture fees from AbbVie, Mitsubishi Tanabe Pharma, Zeria, Mochida Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., and Janssen and has received research grants from AbbVie, Mitsubishi Tanabe Pharma, EA Pharma Co., Ltd., JIMRO Co., Ltd., Mochida Pharmaceutical Co., Ltd., and Kissei. M.W. received lecture fees from Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd., Astellas Pharma Inc., Nippon Ka­yaku Co., Ltd., Mochida Pharmaceutical Co., Ltd., Pfizer Japan Inc., Janssen Pharmaceutical KK, Kissei Pharmaceutical Co., Ltd., Celltrion Healthcare Co., Ltd., Celgene KK, and Gilead Sciences, Inc., consultancy fees from Takeda Pharmaceutical Co., Ltd., Abb­Vie GK, EA Pharma Co., Ltd., Eli Lilly Japan KK, Gilead Sciences, Inc., and research funding from Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd., Astellas Pharma Inc., MSD KK, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Mochida Pharmaceutical Co., Ltd., Ayumi Pharmaceutical Corporation, Miyarisan Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Asahi Kasei Medical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., AbbVie GK, Kyowa Hakko Kirin Co., Ltd., EA Pharma Co., Ltd., Pfizer Japan Inc., Kissei Pharmaceutical Co., Ltd., Kaken Pharmaceutical Co., Ltd., Alfresa Pharma Corporation, Toray Industries, Inc., Chugai Pharmaceutical Co., Ltd., Gilead Sciences, Inc., and Fujirebio Inc. T.H. received lecture fees from Aspen Japan KK, AbbVie GK, Ferring, Gilead Sciences, Janssen, JIMRO, Kisse Pharmaceutical, Mitsubishi-Tanabe Pharma, Mochida Pharmaceutical, ­Nippon Kayaku Pfizer, Takeda Pharmaceutical, and Zeria Pharmaceutical, advisory/consultancy fees from AbbVie, Bristol-Myers Squibb, Celltrion, EA Pharma, Eli Lilly, Gilead Sciences, Janssen, Kyorin, Mitsubishi-Tanabe Pharma, Nichi-Iko Pharmaceutical, Pfizer, Takeda Pharmaceutical, and Zeria Pharmaceutical, and research grants from AbbVie, EA Pharma, JIMRO, Otuska Holdings, and Zeria Pharmaceuticals.

Figures

Fig. 1
Fig. 1
Concept of primary nonresponders (PNR) and partial responders (PR) after the induction of TNF-α inhibitors.
See this image and copyright information in PMC

References

    1. Verstockt B, Ferrante M, Vermeire S, Van Assche G. New treatment options for inflammatory bowel diseases. J Gastroenterol. 2018 May;53((5)):585–90. - PMC - PubMed
    1. Matsuoka K, Kobayashi T, Ueno F, Matsui T, Hirai F, Inoue N, et al. Evidence-based clinical practice guidelines for inflammatory bowel disease. J Gastroenterol. 2018 Mar;53((3)):305–53. - PMC - PubMed
    1. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, et al. SONIC Study Group Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010 Apr;362((15)):1383–95. - PubMed
    1. Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. ACCENT I Study Group Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002 May;359((9317)):1541–9. - PubMed
    1. Papamichael K, Van Stappen T, Jairath V, Gecse K, Khanna R, D'Haens G, et al. Review article: pharmacological aspects of anti-TNF biosimilars in inflammatory bowel diseases. Aliment Pharmacol Ther. 2015 Nov;42((10)):1158–69. - PubMed