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Fcγ receptor IIIb polymorphism and use of glucocorticoids at baseline are associated with infusion reactions to infliximab in patients with rheumatoid arthritis
  1. Ayumi Okuyama1,
  2. Hayato Nagasawa1,
  3. Katsuya Suzuki1,
  4. Hideto Kameda1,2,
  5. Harumi Kondo2,
  6. Kouichi Amano1,
  7. Tsutomu Takeuchi1,2
  1. 1Rheumatology/Clinical Immunology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
  2. 2Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
  1. Correspondence to Professor Tsutomu Takeuchi, 35 Shinanomachi, Shinjuku-ku, Tokyo 160–8582, Japan; tsutake{at}z5.keio.jp

Abstract

Objective Infusion reaction is a major adverse event in patients with rheumatoid arthritis (RA) treated with infliximab. The possible factors including Fcγ receptor (FcγR) polymorphism associated with the development of infusion reactions in patients with RA receiving infliximab were prospectively examined.

Methods 96 patients with RA were enrolled and scheduled to receive infliximab at a dose of 3 mg/kg at weeks 0, 2 and 6 and every 8 weeks thereafter. Genetic polymorphisms for FcγR were examined in FCGR3A 176F/V and FCGR3B NA1/2 alleles by allele-specific PCR analysis.

Results An infusion reaction was observed in 17 patients (18%) during 52 weeks of treatment with infliximab. The FCGR3B NA1/NA1 genotype was found in 75% of the patients with infusion reactions and in only 37% of those without (p=0.01), whereas the FCGR3A 176F/V genotype was equally distributed in the patients with or without infusion reactions. Glucocorticoids were used in 53% of the patients who developed an infusion reaction and in 80% of those without an infusion reaction (p=0.02). A multivariable logistic regression model showed that the FCGR3B NA1/NA1 genotype and use of glucocorticoids at baseline could be used as independent predictive factors for infusion reactions (OR 6.1 (95% CI 1.9 to 24.3) and OR 0.26 (95% CI 0.08 to 0.84), respectively). The presence of anti-infliximab antibody during infliximab treatment was also associated with infusion reactions.

Conclusion FCGR3B NA1/NA1 genotype, use of glucocorticoids and the presence of anti-infliximab antibody accounted for nearly all patients with RA who developed infusion reactions.

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Footnotes

  • Funding Part of this study was supported by a Research Grant-In-Aid for Scientific Research by the Ministry of Health, Labour and Welfare of Japan.

  • Competing interests None of authors are industry employees. TT has received consultant fees from Mitsubishi-Tanabe Pharma, Bristol-Myers-Squibb and Novartis, and lecture fees from Mitsubishi-Tanabe Pharma, Takeda Pharmaceutical, Abbott, Eisai Pharma and Chugai Pharma. HK received honoraria from Mitsubishi-Tanabe Pharma, Centocor, Wyeth Japan, Takeda Pharmaceutical, Abbott, Eisai Pharma and Chugai Pharma.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the internal review board of Saitama Medical University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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