Skip to main content

Advertisement

SpringerLink
Log in

Comparison of efficacy between anti-IL-6 receptor antibody and other biological disease-modifying antirheumatic drugs in the patients with rheumatoid arthritis who have knee joint involvement: the ANSWER cohort, retrospective study

  • Cohort Studies
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Objective

We aimed to investigate the efficacy of anti-IL-6 receptor antibody (aIL-6) and other biologic disease-modifying antirheumatic drugs (bDMARDs), such as TNF inhibitor and CTLA4-Ig in the treatment of rheumatoid arthritis (RA) in patients with knee joint involvement.

Methods

We retrospectively analyzed 1059 treatment courses of patients with RA who visited our hospitals and were treated with bDMARDs. We categorized them into two groups, with or without knee joint involvement. We investigated the clinical disease activity index (CDAI) at baseline and 12 weeks after the initiation of bDMARDs. We compared the improvement of the markers between aIL-6 and other bDMARDs.

Results

Treatment with aIL-6 significantly increased ΔCDAI (n = 91, 15.4 ± 1.1; mean ± SEM) in patients with knee joint involvement, compared to other bDMARDs (n = 232, 11.0 ± 0.7) at 12 weeks (P = 0.006). Following the multivariate analysis adjusted by the CDAI levels at baseline, age, gender, concomitant use of methotrexate, and the first use of bDMARDs, ΔCDAI levels were significantly higher in aIL-6, compared to other bDMARDs (P = 0.02). However, there was no significant difference in ΔCDAI improvement between aIL-6 (n = 162, 5.9 ± 0.6) and other bDMARDs (n = 573, 6.2 ± 0.4) in patients without swollen knee joints. ΔCDAI levels were equally increased in patients with shoulder and elbow joint involvement.

Conclusion

aIL-6 was more effective in the patients with RA and knee joint involvement, compared to other bDMARDs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Scott DL, Wolfe F, Huizinga TW (2010) Rheumatoid arthritis. Lancet 376(9746):1094–1108. https://doi.org/10.1016/s0140-6736(10)60826-4

    Article  PubMed  Google Scholar 

  2. Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K et al (2016) Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine. Arthritis Rheumatol 68(11):2646–2661. https://doi.org/10.1002/art.39783

    Article  CAS  PubMed  Google Scholar 

  3. Kishikawa T, Maeda Y, Nii T, Motooka D, Matsumoto Y, Matsushita M et al (2020) Metagenome-wide association study of gut microbiome revealed novel aetiology of rheumatoid arthritis in the Japanese population. Ann Rheum Dis 79(1):103–111. https://doi.org/10.1136/annrheumdis-2019-215743

    Article  CAS  PubMed  Google Scholar 

  4. Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K et al (2014) Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506(7488):376–381. https://doi.org/10.1038/nature12873

    Article  CAS  PubMed  Google Scholar 

  5. Hashimoto M, Yamazaki T, Hamaguchi M, Morimoto T, Yamori M, Asai K et al (2015) Periodontitis and Porphyromonas gingivalis in preclinical stage of arthritis patients. PLoS ONE 10(4):e0122121. https://doi.org/10.1371/journal.pone.0122121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Nishimoto N, Hashimoto J, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T et al (2007) Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an X ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis 66(9):1162–1167. https://doi.org/10.1136/ard.2006.068064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Aletaha D, Smolen JS (2018) Diagnosis and management of rheumatoid arthritis: a review. JAMA 320(13):1360–1372. https://doi.org/10.1001/jama.2018.13103

    Article  PubMed  Google Scholar 

  8. Narazaki M, Tanaka T, Kishimoto T (2017) The role and therapeutic targeting of IL-6 in rheumatoid arthritis. Expert Rev Clin Immunol 13(6):535–551. https://doi.org/10.1080/1744666x.2017.1295850

    Article  CAS  PubMed  Google Scholar 

  9. Bijlsma JWJ, Welsing PMJ, Woodworth TG, Middelink LM, Pethö-Schramm A, Bernasconi C et al (2016) Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet 388(10042):343–355. https://doi.org/10.1016/s0140-6736(16)30363-4

    Article  CAS  PubMed  Google Scholar 

  10. Linn-Rasker SP, van der Helm-van Mil AH, Breedveld FC, Huizinga TW (2007) Arthritis of the large joints—in particular, the knee—at first presentation is predictive for a high level of radiological destruction of the small joints in rheumatoid arthritis. Ann Rheum Dis 66(5):646–650. https://doi.org/10.1136/ard.2006.066704

    Article  CAS  PubMed  Google Scholar 

  11. Nakagawa J, Koyama Y, Kawakami A, Ueki Y, Tsukamoto H, Horiuchi T et al (2017) A novel scoring system based on common laboratory tests predicts the efficacy of TNF-inhibitor and IL-6 targeted therapy in patients with rheumatoid arthritis: a retrospective, multicenter observational study. Arthritis Res Ther 19(1):185. https://doi.org/10.1186/s13075-017-1387-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lansbury J, Haut DD (1956) Quantitation of the manifestations of rheumatoid arthritis. 4. Area of joint surfaces as an index to total joint inflammation and deformity. Am J Med Sci. 232(2):150–155

    Article  CAS  PubMed  Google Scholar 

  13. Hashimoto M, Furu M, Yamamoto W, Fujimura T, Hara R, Katayama M et al (2018) Factors associated with the achievement of biological disease-modifying antirheumatic drug-free remission in rheumatoid arthritis: the ANSWER cohort study. Arthritis Res Ther 20(1):165. https://doi.org/10.1186/s13075-018-1673-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ebina K, Hirano T, Maeda Y, Yamamoto W, Hashimoto M, Murata K et al (2020) Drug retention of 7 biologics and tofacitinib in biologics-naïve and biologics-switched patients with rheumatoid arthritis: the ANSWER cohort study. Arthritis Res Ther 22(1):142. https://doi.org/10.1186/s13075-020-02232-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ebina K, Hirano T, Maeda Y, Yamamoto W, Hashimoto M, Murata K et al (2020) Drug retention of secondary biologics or JAK inhibitors after tocilizumab or abatacept failure as first biologics in patients with rheumatoid arthritis—the ANSWER cohort study. Clin Rheumatol 39(9):2563–2572. https://doi.org/10.1007/s10067-020-05015-5

    Article  PubMed  Google Scholar 

  16. Jinno S, Onishi A, Dubreuil M, Akashi K, Hashimoto M, Yamamoto W et al (2020) Comparison of the efficacy and safety of biologic agents between elderly-onset and young-onset RA patients: the ANSWER cohort study. Rheumatol Int. https://doi.org/10.1007/s00296-020-04660-y

    Article  PubMed  Google Scholar 

  17. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324. https://doi.org/10.1002/art.1780310302

    Article  CAS  PubMed  Google Scholar 

  18. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO III et al (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62(9):2569–2581. https://doi.org/10.1002/art.27584

    Article  PubMed  Google Scholar 

  19. Thompson PW, Silman AJ, Kirwan JR, Currey HL (1987) Articular indices of joint inflammation in rheumatoid arthritis. Correlation with the acute-phase response. Arthritis Rheum 30(6):618–623. https://doi.org/10.1002/art.1780300603

    Article  CAS  PubMed  Google Scholar 

  20. Lansbury J (1968) Clinical appraisal of the activity index as a measure of rheumatoid activity. Arthritis Rheum 11(4):599–604. https://doi.org/10.1002/art.1780110411

    Article  CAS  PubMed  Google Scholar 

  21. Holt I, Cooper RG, Hopkins SJ (1991) Relationships between local inflammation, interleukin-6 concentration and the acute phase protein response in arthritis patients. Eur J Clin Investig 21(5):479–484. https://doi.org/10.1111/j.1365-2362.1991.tb01398.x

    Article  CAS  Google Scholar 

  22. Chen DY, Hsieh TY, Chen YM, Hsieh CW, Lan JL, Lin FJ (2009) Proinflammatory cytokine profiles of patients with elderly-onset rheumatoid arthritis: a comparison with younger-onset disease. Gerontology 55(3):250–258. https://doi.org/10.1159/000164393

    Article  CAS  PubMed  Google Scholar 

  23. Yoshihara Y, Obata K, Fujimoto N, Yamashita K, Hayakawa T, Shimmei M (1995) Increased levels of stromelysin-1 and tissue inhibitor of metalloproteinases-1 in sera from patients with rheumatoid arthritis. Arthritis Rheum 38(7):969–975. https://doi.org/10.1002/art.1780380713

    Article  CAS  PubMed  Google Scholar 

  24. Sasaki S, Iwata H, Ishiguro N, Obata K, Miura T (1994) Detection of stromelysin in synovial fluid and serum from patients with rheumatoid arthritis and osteoarthritis. Clin Rheumatol 13(2):228–233. https://doi.org/10.1007/bf02249017

    Article  CAS  PubMed  Google Scholar 

  25. Gorai M, Ogasawara M, Matsuki Y, Yamada Y, Murayama G, Sugisaki N et al (2014) Weighting with the Lansbury Articular Index improves the correlation of ultrasound score with serum matrix metalloproteinase-3 level in rheumatoid arthritis patients. Mod Rheumatol 24(6):915–919. https://doi.org/10.3109/14397595.2014.888794

    Article  CAS  PubMed  Google Scholar 

  26. Lipina M, Makarov M, Makarov S, Novikov A (2017) The degree of cartilage degradation assessed by serum biomarker levels changes after arthroscopic knee synovectomy in rheumatoid arthritis patients. Int Orthop 41(11):2259–2264. https://doi.org/10.1007/s00264-017-3634-8

    Article  PubMed  Google Scholar 

  27. Kobayashi A, Naito S, Enomoto H, Shiomoi T, Kimura T, Obata K et al (2007) Serum levels of matrix metalloproteinase 3 (stromelysin 1) for monitoring synovitis in rheumatoid arthritis. Arch Pathol Lab Med 131(4):563–570. https://doi.org/10.1043/1543-2165(2007)131[563:Slomms]2.0.Co;2

    Article  CAS  PubMed  Google Scholar 

  28. Wang J, Devenport J, Low JM, Yu D, Hitraya E (2016) Relationship between baseline and early changes in C-reactive protein and interleukin-6 levels and clinical response to tocilizumab in rheumatoid arthritis. Arthritis Care Res (Hoboken) 68(6):882–885. https://doi.org/10.1002/acr.22765

    Article  CAS  Google Scholar 

  29. Zhang W, Doherty M, Peat G, Bierma-Zeinstra MA, Arden NK, Bresnihan B et al (2010) EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis. Ann Rheum Dis 69(3):483–489. https://doi.org/10.1136/ard.2009.113100

    Article  CAS  PubMed  Google Scholar 

  30. Hussain SM, Neilly DW, Baliga S, Patil S, Meek R (2016) Knee osteoarthritis: a review of management options. Scott Med J 61(1):7–16. https://doi.org/10.1177/0036933015619588

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all the physicians who evaluated detailed joint findings at Kyoto University Hospital, Osaka Medical College Hospital, Osaka Red Cross Hospital, Kansai Medical University Hospital, Kobe University Hospital, Nara Medical University Hospital and Osaka University Hospital. English language editing was performed by editage.

Funding

ANSWER Cohort is supported by grants from pharmaceutical companies (Abbie G.K., Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Sanofi, UCB Japan Co. Ltd., Teijin Healthcare Limited) and an information technology services company (CAC). These companies had no roles in study design, data collection, data analysis, data interpretation or writing of the manuscript.

Author information

Authors and Affiliations

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

    Yuichi Maeda, Toru Hirano & Atsushi Kumanogoh

  2. Department of Musculoskeletal Regenerative Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

    Kosuke Ebina

  3. The Center for Rheumatic Diseases, Nara Medical University, Kashihara, Japan

    Ryota Hara

  4. Department of Advanced Medicine for Rheumatic Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Motomu Hashimoto

  5. Health Information Management, Kurashiki Sweet Hospital, Kurashiki, Japan

    Wataru Yamamoto

  6. Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Kosaku Murakami

  7. Department of Internal Medicine (IV), Osaka Medical College, Takatsuki, Japan

    Takuya Kotani & Kenichiro Hata

  8. First Department of Internal Medicine, Kansai Medical University, Hirakata, Japan

    Yonsu Son & Hideki Amuro

  9. Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan

    Akira Onishi & Sadao Jinno

  10. Department of Rheumatology, Osaka Red Cross Hospital, Osaka, Japan

    Masaki Katayama

  11. Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan

    Yuichi Maeda & Atsushi Kumanogoh

Authors
  1. Yuichi Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toru Hirano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kosuke Ebina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ryota Hara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Motomu Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wataru Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kosaku Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Takuya Kotani
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kenichiro Hata
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yonsu Son
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hideki Amuro
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Akira Onishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Sadao Jinno
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Masaki Katayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Atsushi Kumanogoh
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceived and designed the study: YM. Analyzed the data: YM, collection of data: YM, TH, KE, RH, MH, WY, KM, TK, KH, YS, HA, AO, SJ, MK, AK. YM 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 as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Yuichi Maeda.

Ethics declarations

Conflict of interest

YM received a research grant and/or speaker fee from Eli Lilly Japan K.K., Chugai Pharmaceutical Co. Ltd., Pfizer Inc., Bristol Myers Squibb, and Mitsubishi Tanabe Pharma Corporation. TH received a speaker fee from GlaxoSmithKline, Chugai, Eisai, Eli Lilly and NIPPON SHINYAKU. KE is affiliated with the department, which is supported by Taisho. KE has received research grants from Abbie, Asahi-Kasei, Astellas, Chugai, Eisai, Ono Pharmaceutical, and UCB Japan. K.E. has received payments for lectures from Abbie, Asahi-Kasei, Astellas, AYUMI, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Janssen, Mitsubishi Tanabe, Ono Pharmaceutical, Sanofi and UCB Japan. MH belong to the department that is financially supported by Nagahama City, Shiga, Japan, Toyooka City, Hyogo, Japan and five pharmaceutical companies (Mitsubishi-Tanabe, Chugai, UCB Japan, AYUMI and Asahi-Kasei). MH has received a research and/or speaker fee from Bristol-Meyers, Eisai, Ely Lilly, and Tanabe-Mitsubishi. JS reports personal fees from Mitsubishi Tanabe Pharma Corporation, personal fees from Chugai Pharmaceutical Co. Ltd, personal fees from Asahi-Kasei Corporation, personal fees from Eli Lilly and Company, personal fees from AbbVie GK. KM received a research grant from Eisai. AO received a speaker fee from Chugai, Ono Pharmaceutical, Eli Lilly, Mitsubishi Tanabe, Asahi-Kasei and Takeda. AK received a research grant and/or speaker fee from Mitsubishi-Tanabe, Chugai, Eisai, Asahi-Kasei, Astellas, Abbie, Bristol-Myers Squibb, Ono Pharmaceutical and Pfizer.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 47 kb)

Supplementary file2 (PPTX 580 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maeda, Y., Hirano, T., Ebina, K. et al. Comparison of efficacy between anti-IL-6 receptor antibody and other biological disease-modifying antirheumatic drugs in the patients with rheumatoid arthritis who have knee joint involvement: the ANSWER cohort, retrospective study. Rheumatol Int 41, 1233–1241 (2021). https://doi.org/10.1007/s00296-021-04862-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-021-04862-y

Keywords

Search

Navigation