A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn’s disease☆
Open accessAbstract
Background & aims Interleukin-6 (IL-6) regulates immune response and inflammation. We carried out a pilot placebo-controlled study to investigate the efficacy, pharmacokinetics, and safety of MRA, a humanized monoclonal antibody to IL-6 receptor, in patients with active Crohn's disease. Methods Thirty-six patients with active Crohn's disease (Crohn's Disease Activity Index [CDAI] > or =150) were randomly assigned to receive biweekly intravenous infusion of either placebo, MRA, or MRA/placebo alternately for 12 weeks at a dose of 8 mg/kg. The study's primary end point was a clinical response rate that was defined as a reduction of CDAI > or =70. Results At the final evaluation, 80% of the patients (8 of 10) given biweekly MRA had a clinical response as compared with 31% of the placebo-treated patients (4 of 13; P = 0.019). Twenty percent of the patients (2 of 10) on this regimen went into remission (CDAI <150), as compared with 0% of the placebo-treated patients (0 of 13). The clinical response rate of the every-4-week regimen was 42% (5 of 12). The serum concentrations of MRA were detected at 2 weeks after every infusion, at which time acute phase responses were completely suppressed; however, they were not suppressed at 4 weeks. Endoscopic and histologic examination showed no difference between MRA and placebo groups. The incidence of adverse events was similar in all the groups. Conclusions This is the first clinical trial of humanized anti-IL-6 receptor monoclonal antibody in Crohn's disease. A biweekly 8 mg/kg infusion of MRA was well tolerated, normalized the acute-phase responses, and suggests a clinical effect in active Crohn's disease.
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In tissue-specific immune-mediated diseases including IBD, therapies that inhibit IL-6 signaling have not gained clinical use despite evidence that antibodies targeting IL-6 or IL-6Rα may have efficacy.
“This is in contrast to tissue-specific immune-mediated diseases, including IBD, where therapies that inhibit IL-6 signaling have not gained clinical use despite evidence that antibodies targeting IL-6 or IL-6Rα may have efficacy (83).”
From T <sub>H</sub> 17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity (2020) · cites this paper as [83]
The Clinical Response to Treatment section (page not supplied) reports a higher response rate with an anti-IL-6 receptor antibody than with placebo in active Crohn’s disease, supporting possible efficacy in IBD. The paper does not establish whether IL-6-inhibiting therapies gained clinical use, nor does its trial address tissue-specific immune-mediated diseases beyond Crohn’s disease. (LLM, conf=0.87)
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- Authors
- Ito, H., Takazoe, M., Fukuda, Y., Hibi, T., Kusugami, K., Andoh, A., Matsumoto, T., Yamamura, T., Azuma, J., & Nishimoto, N.
- Affiliations
- The University of Osaka (JP)
- Tokyo Yamate Medical Center (JP)
- Hyogo Medical University (JP)
- Nagoya University Hospital (JP)
- Shiga University of Medical Science (JP)
- Osaka City University (JP)
- Corresponding author
- Ito, Hiroaki
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 126
- Issue
- 4
- Pages
- 989-996
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2118877038
- Cited by
- 636
- References
- 0
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 16 · 2023: 24 · 2022: 13 · 2021: 24 · 2020: 22 · 2019: 23 · 2018: 29 · 2017: 31 · 2016: 27 · 2015: 22 · 2014: 38 · 2013: 34 · 2012: 33
- FWCI
- 23.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- Crohn's disease, IL-6 receptor, anti-IL-6 receptor monoclonal antibody, MRA, humanized monoclonal antibody, CDAI, clinical response, remission, pharmacokinetics, acute phase response, adverse events
- MeSH terms
- Adult, Antibodies, Monoclonal, Crohn Disease, Female, Humans, Male, Pilot Projects, Signal Transduction, Biomarkers, Treatment Outcome, Receptors, Interleukin-6
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