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The family history of rheumatoid arthritis in anti-cyclic citrullinated peptide antibody-positive patient is not a predictor of poor clinical presentation and treatment response with modern classification criteria and treatment strategy: the ANSWER cohort study

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Abstract

A family history of rheumatoid arthritis (RA) is a strong risk factor for developing RA, affecting both genetically and environmentally. However, whether family history provides clinically relevant information in the modern classification and treatment remains largely unknown. This study aimed to determine whether a family history of RA is associated with a different clinical presentation of RA and treatment response. We retrospectively evaluated the demographic data and disease activity of newly diagnosed RA patients at baseline, 1 year, and 2 years after onset, using the ANSWER (Kansai consortium for the well-being of rheumatic disease patients) cohort data. Thirty-one patients (11.9%) among 260 newly diagnosed RA patients had a family history of RA up to second degree. There was no significant difference in the age at onset, time from onset to first visit, sex, positivity or value of rheumatoid factor or anti-cyclic citrullinated peptide antibody (ACPA), or disease activity between patients with and without a family history of RA. However, patients who had a family history of RA and were ACPA positive showed significantly lower erythrocyte sedimentation rate, and C-reactive protein. Disease activity in patients with a family history was not worse at baseline, after 1 year or 2 years of treatment. The Larsen score 2 years after onset was equivalent between the patients with and without a family history of RA in ACPA-positive patients. Family history of RA in ACPA-positive patients is not associated with high disease activity at baseline and is not a predictor of poor outcome 2 years after onset.

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Acknowledgements

We wish to thank all medical staff at all institutions participating in the ANSWER cohort for providing the data. This manuscript was proofread by Enago, Academic Proofreading Service.

Funding

The study reported in this publication uses ANSWER Cohort supported by grants from five pharmaceutical companies (Chugai Pharmaceutical Co. Ltd, Eisai Co., Ltd., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Ltd. and Sanofi S.A.) and an information technology services company (CAC). Department of Advanced Medicine for Rheumatic Diseases, Kyoto University Graduate School of Medicine is supported by Nagahama City, Shiga, Japan and four pharmaceutical companies (Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co. Ltd, UCB Japan Co. Ltd, and AYUMI Pharmaceutical Co.). KURAMA cohort study, one of cohorts consisting ANSWER cohort, is supported by grant from Daiichi Sankyo Co. Ltd. KN and TT belongs to the department which is financially supported by four pharmaceutical companies (Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Asahi Kasei Pharma Corporation, Eisai Co., Takeda Pharmaceutical Company Limited). This study is conducted as investigator-initiated study. These companies had no role in the design of the study, the collection or analysis of the data, the writing of the manuscript or decision to submit the manuscript for the publication.

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Authors and Affiliations

  1. Department of Advanced Medicine for Rheumatic Diseases, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan

    Koichi Murata, Motomu Hashimoto, Wataru Yamamoto & Masao Tanaka

  2. Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Shogoin, Kyoto, Japan

    Koichi Murata, Hiromu Ito & Shuichi Matsuda

  3. Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Kyoto, Japan

    Motomu Hashimoto, Kosaku Murakami, Masao Tanaka & Tsuneyo Mimori

  4. Department of Health Information Management, Kurashiki Sweet Hospital, 3542-1 Nakasho, Kurashiki, 710-0016, Japan

    Wataru Yamamoto

  5. First Department of Internal Medicine, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, 573-1010, Japan

    Yonsu Son & Hideki Amuro

  6. Department of Internal Medicine (IV), Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, 569-8686, Japan

    Koji Nagai & Tohru Takeuchi

  7. Department of Rheumatology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji, Osaka, 543-8555, Japan

    Masaki Katayama

  8. Department of Respiratory Medicine and Clinical Immunology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan

    Yuichi Maeda

  9. Department of Musculoskeletal Regenerative Medicine, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan

    Kosuke Ebina

  10. Department of Orthopedic Surgery, The Center for Rheumatic Diseases, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan

    Ryota Hara

  11. Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo, Kobe, 650-0017, Japan

    Sadao Jinno & Akira Onishi

  12. Ijinkai Takeda General Hospital, 28-1 Ishidamoriminami-cho, Fushimi, Kyoto, 601-1495, Japan

    Tsuneyo Mimori

Authors
  1. Koichi Murata
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  2. Motomu Hashimoto
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  3. Wataru Yamamoto
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  4. Yonsu Son
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  5. Hideki Amuro
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  6. Koji Nagai
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  7. Tohru Takeuchi
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  8. Masaki Katayama
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  9. Yuichi Maeda
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  10. Kosuke Ebina
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  11. Ryota Hara
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  12. Sadao Jinno
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  13. Akira Onishi
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  14. Kosaku Murakami
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  15. Masao Tanaka
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  16. Hiromu Ito
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  17. Tsuneyo Mimori
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  18. Shuichi Matsuda
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Contributions

KM conceived and designed the study. KM, MH, WS, HA, KN, TT, MK, YM KE, RH, SJ, AO, KM, MT, HI, TM, and SM recruited the patients and collected the data. KM and WY analyzed the data. KM prepared the initial draft of the manuscript. All the authors were involved in revising the manuscript critically for content. All authors read and approved the final manuscript. They also agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Koichi Murata.

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Conflict of interest

KMurat received a speaking fee and/or consulting fee from Eisai Co., Ltd. MH received a research grant and/or speaker fee from Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, and Bristol-Myers Squibb. TT is affiliated with a department that is financially supported by six pharmaceutical companies (Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co. Ltd, AYUMI Pharmaceutical Co., Astellas Pharma, Eisai Co., Ltd., and Takeda Pharmaceutical Company Limited). KN received a research grant and/or speaker fee from Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Bristol-Myers Squibb, Eli Lily, Pfizer Inc, Janssen Pharmaceutical K.K., UCB Japan Co. Ltd, and Asahi Kasei Pharma Corporation. TT received a research grant from Chugai Pharmaceutical Co. Ltd, and a speaker fee from Astellas Pharma Inc., Chugai Pharmaceutical Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Bristol-Myers Squibb, Eli Lily, Pfizer Inc, Janssen Pharmaceutical K.K., UCB Japan Co. Ltd, Astellas Pharma, and Asahi Kasei Pharma Corporation. YM received a research grant and/or speaker fee from Eli Lily, Chugai Pharmaceutical Co. Ltd., Pfizer Inc, Bristol-Myers Squibb and Mitsubishi Tanabe Pharma Corporation. KE received a research grant and/or speaker fee from Asahi Kasei Corporation, Astellas Pharma Inc., Chugai Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Taisho-toyama, and UCB Japan Co. Ltd. SJ received a research grant and/or speaker fee from Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Asahi Kasei Pharma Corporation, Eli Lilly and Company, and AbbVie GK. KMurak has received speaking fees, and/or consulting fees from Eisai Co. Ltd, Chugai Pharmaceutical Co. Ltd., Pfizer Inc., Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Corporation, UCB Japan Co. Ltd, Daiichi Sankyo Co. Ltd. and Astellas Pharma Inc. M.T. has received research grants and/or speaker fees from AbbVie GK, Asahi Kasei Pharma Corporation, Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly and Company, Pfizer Inc., UCB Japan Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Taisho Pharma Co., Ltd, and Takeda Pharmaceutical Company Limited,. H.I. has received a research grant and/or speaker fee from Bristol-Myers Squibb, Astellas Pharma Inc., Asahi Kasei Pharma Corporation, and Kyocera Medical Co. TM has received research grants and/or speakers’ fees from Astellas Pharma Inc., Asahi Kasei Corporation, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Pfizer Inc., and Sanofi S.A. SM has received a research grant and/or speaker fee from Eisai Co., Ltd., Chugai Pharmaceutical Co. Ltd, and Ono Pharmaceutical Co. All other authors have declared no conflicts of interests.

Ethics approval

This observational study was conducted as per the Declaration of Helsinki and was approved by the ethics committees of all seven institutes: Kyoto University (2016-03-24/approved number R053), Osaka University (2015-11-04/approved number 15300), Osaka Medical College (2014-07-14/approved number 1529), Kansai Medical University (2017-11-21/approved number 2014625), Kobe University (2015-03-20/approved number 1738), Nara Medial University (2018-01-23/approved number 1692), and Osaka Red Cross Hospital (2015-09-01/approved number 644).

Informed consent

The board of Osaka University Hospital Ethical Committee waived the requirement for patients’ informed consent because of the anonymous nature of the data. Written informed consent was obtained from the participants in other institutes.

Plagiarism

No parts of the manuscript were copied from elsewhere.

Prior conference presentation

Part of the data was presented at the 63rd annual general assembly and scientific meeting of the Japan College of Rheumatology and the 5th annual meeting of Japanese Society of Osteoimmunogy.

Congress abstract

Koichi Murata, Motomu Hashimoto, Wataru Yamamoto, Yonsu Son, Hideki Amuro, Koji Nagai, Tohru Takeuchi, Masaki Katayama, Yuichi Maeda, Kosuke Ebina, Ryota Hara, Sadao Jinno, Akira Onishi, Kosaku Murakami, Masao Tanaka, Hiromu Ito, Tsuneyo Mimori and Shuichi Matsuda. Does a family history of RA influence the clinical presentation and treatment response in RA? ANSWER Cohort—[abstract] In: the 63rd annual general assembly and scientific meeting of the Japan College of Rheumatology; 2019 Apr 15–14; Kyoto, Kyoto, Japan. Abstract nr P3-007. Koichi Murata, Motomu Hashimoto, Wataru Yamamoto, Yonsu Son, Hideki Amuro, Koji Nagai, Tohru Takeuchi, Masaki Katayama, Yuichi Maeda, Kosuke Ebina, Ryota Hara, Sadao Jinno, Akira Onishi, Kosaku Murakami, Masao Tanaka, Hiromu Ito, Tsuneyo Mimori and Shuichi Matsuda. Does a family history of RA influence the clinical presentation and treatment response in RA? ANSWER Cohort—[abstract] In: the 5th annual meeting of Japanese Society of Osteoimmunogy; 2019 June 25–27; Ishigaki, Okinawa, Japan. Abstract nr P2-1.

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Murata, K., Hashimoto, M., Yamamoto, W. et al. The family history of rheumatoid arthritis in anti-cyclic citrullinated peptide antibody-positive patient is not a predictor of poor clinical presentation and treatment response with modern classification criteria and treatment strategy: the ANSWER cohort study. Rheumatol Int 40, 217–225 (2020). https://doi.org/10.1007/s00296-019-04464-9

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