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  • Review Article
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Global epidemiology of rheumatoid arthritis

Nature Reviews Rheumatology volume 18, pages 591–602 (2022)Cite this article

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Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease that predominantly affects the joints. The prevalence of RA varies globally, with generally a higher prevalence in industrialized countries, which may be explained by exposures to environmental risk factors, but also by genetic factors, differing demographics and under-reporting in other parts of the world. Over the past three decades, strong trends of the declining severity of RA probably reflect changes in treatment paradigms and overall better management of the disease. Other trends include increasing RA prevalence. Common risk factors for RA include both modifiable lifestyle-associated variables and non-modifiable features, such as genetics and sex. A better understanding of the natural history of RA, and of the factors that contribute to the development of RA in specific populations, might lead to the introduction of specific prevention strategies for this debilitating disease.

Key points

  • The estimated prevalence and disease burden of rheumatoid arthritis (RA) vary considerably between geographic regions, with generally higher estimates in industrialized countries and urban settings.

  • Aspects involved in the disparity in RA prevalence between populations include genetic factors, environmental exposures, demographics, socioeconomics and reporting of the disease.

  • Despite rising RA prevalence, the severity, mortality and disease-associated comorbidities seem to be decreasing.

  • The aetiopathogenesis of RA involves interaction between predisposing genetic factors and environmental triggers, mostly at mucosal sites (oral cavity, respiratory system and intestinal tract), resulting in the ‘mucosal origin’ hypothesis.

  • Many RA risk factors are modifiable, including dietary habits and inhalation of pollutants such as tobacco smoke; modifications are being incorporated in prevention strategies.

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Fig. 1: Global prevalence of rheumatoid arthritis.
Fig. 2: Known risk factors for rheumatoid arthritis.

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References

  1. Birnbaum, H. et al. Societal cost of rheumatoid arthritis patients in the US. Curr. Med. Res. Opin. 26, 77–90 (2010).

    Article  PubMed  Google Scholar 

  2. Joensuu, J. T. et al. The cost-effectiveness of biologics for the treatment of rheumatoid arthritis: a systematic review. PLoS ONE 10, e0119683 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  3. O’Rourke, J. A. et al. Accuracy of self-reported history of autoimmune disease: a pilot study. PLoS ONE 14, e0216526 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Karison, E. W. et al. Comparison of self-reported diagnosis of connective tissue disease with medical records in female health professionals: the Women’s Health Cohort Study. Am. J. Epidemiol. 150, 652–660 (1999).

    Article  Google Scholar 

  5. Videm, V., Thomas, R., Brown, M. A. & Hoff, M. Self-reported diagnosis of rheumatoid arthritis or ankylosing spondylitis has low accuracy: data from the Nord-Trøndelag Health Study. J. Rheumatol. 44, 1134–1141 (2017).

    Article  PubMed  Google Scholar 

  6. James, S. L. et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392, 1789–1858 (2018).

    Article  Google Scholar 

  7. Safiri, S. et al. Global, regional and national burden of rheumatoid arthritis 1990–2017: a systematic analysis of the Global Burden of Disease Study 2017. Ann. Rheum. Dis. 78, 1463–1471 (2019).

    Article  PubMed  Google Scholar 

  8. Murray, C. J. L. et al. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 396, 1223–1249 (2020).

    Article  Google Scholar 

  9. GEO-RA Group. Latitude gradient influences the age of onset of rheumatoid arthritis: a worldwide survey. Clin. Rheumatol. 36, 485–497 (2017).

    Article  Google Scholar 

  10. Bae, S.-C., Fraser, P. & Liang, M. H. The epidemiology of systemic lupus erythematosus in populations of African ancestry: a critical review of the “prevalence gradient hypothesis”. Arthritis Rheum. 41, 2091–2099 (1998).

    Article  CAS  PubMed  Google Scholar 

  11. Almutairi, K., Nossent, J., Preen, D., Keen, H. & Inderjeeth, C. The global prevalence of rheumatoid arthritis: a meta-analysis based on a systematic review. Rheumatol. Int. 41, 863–877 (2021).

    Article  PubMed  Google Scholar 

  12. Cross, M. et al. The global burden of rheumatoid arthritis: estimates from the Global Burden of Disease 2010 study. Ann. Rheum. Dis. 73, 1316–1322 (2014).

    Article  PubMed  Google Scholar 

  13. Almutairi, K. B., Nossent, J. C., Preen, D. B., Keen, H. I. & Inderjeeth, C. A. The prevalence of rheumatoid arthritis: a systematic review of population-based studies. J. Rheumatol. 48, 669–676 (2021).

    Article  PubMed  Google Scholar 

  14. Runowska, M., Majewski, D., Niklas, K. & Puszczewicz, M. Chikungunya virus: a rheumatologist’s perspective. Clin. Exp. Rheumatol. 36, 495–501 (2018).

    Google Scholar 

  15. Rojas, M. et al. Ebola virus disease: an emerging and re-emerging viral threat. J. Autoimmun. 106, 102375 (2020).

    Article  CAS  PubMed  Google Scholar 

  16. Mohammed, R. H. A. et al. Prevalence of rheumatologic manifestations of chronic hepatitis C virus infection among Egyptians. Clin. Rheumatol. 29, 1373–1380 (2010).

    Article  PubMed  Google Scholar 

  17. Adizie, T., Moots, R. J., Hodkinson, B., French, N. & Adebajo, A. O. Inflammatory arthritis in HIV positive patients: a practical guide. BMC Infect. Dis. 16, 100 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Amaral, J. K., Bilsborrow, J. B. & Schoen, R. T. Chronic Chikungunya arthritis and rheumatoid arthritis: what they have in common. Am. J. Med. 133, e91–e97 (2020).

    Article  CAS  PubMed  Google Scholar 

  19. Maritz, N. G. J., Gerber, A. J., Greyling, S. J. & Sanda, B. B. A radiological study of the rheumatoid hand in black South Africans. South. Afr. Med. J. 95, 795–797 (2005).

    CAS  Google Scholar 

  20. Bergstra, S. A. et al. Evaluation of the joint distribution at disease presentation of patients with rheumatoid arthritis: a large study across continents. RMD Open 3, e000568 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Mody, G. M. & Cardiel, M. H. Challenges in the management of rheumatoid arthritis in developing countries. Best. Pract. Res. Clin. Rheumatol. 22, 621–641 (2008).

    Article  PubMed  Google Scholar 

  22. Halabi, H. et al. Challenges and opportunities in the early diagnosis and optimal management of rheumatoid arthritis in Africa and the Middle East. Int. J. Rheum. Dis. 18, 268–275 (2015).

    Article  CAS  PubMed  Google Scholar 

  23. Adelowo, O., Mody, G. M., Tikly, M., Oyoo, O. & Slimani, S. Rheumatic diseases in Africa. Nat. Rev. Rheumatol. 17, 363–374 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Davatchi, F. et al. Epidemiology of rheumatic diseases in Iran from analysis of four COPCORD studies. Int. J. Rheum. Dis. 19, 1056–1062 (2016).

    Article  PubMed  Google Scholar 

  25. Kojima, M. et al. Epidemiological characteristics of rheumatoid arthritis in Japan: prevalence estimates using a nationwide population-based questionnaire survey. Mod. Rheumatol. 30, 941–947 (2020).

    Article  PubMed  Google Scholar 

  26. Yang, D.-H., Huang, J.-Y., Chiou, J.-Y. & Wei, J. C.-C. Analysis of socioeconomic status in the patients with rheumatoid arthritis. Int. J. Environ. Res. Public Health 15, 1194 (2018).

    Article  PubMed Central  Google Scholar 

  27. Won, S. et al. Update on the prevalence and incidence of rheumatoid arthritis in Korea and an analysis of medical care and drug utilization. Rheumatol. Int. 38, 649–656 (2018).

    Article  PubMed  Google Scholar 

  28. Li, R. et al. Epidemiology of eight common rheumatic diseases in China: a large-scale cross-sectional survey in Beijing. Rheumatology 51, 721–729 (2012).

    Article  PubMed  Google Scholar 

  29. Abhishek, A. et al. Rheumatoid arthritis is getting less frequent — results of a nationwide population-based cohort study. Rheumatology https://doi.org/10.1093/rheumatology/kew468 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Seoane-Mato, D., Sánchez-Piedra, C., Díaz-González, F. & Bustabad, S. Prevalence of rheumatic diseases in adult population in Spain (EPISER 2016 study): aims and methodology. Ann. Rheum. Dis. 77, 535–536 (2018).

    Google Scholar 

  31. Batko, B. et al. Prevalence and clinical characteristics of rheumatoid arthritis in Poland: a nationwide study. Arch. Med. Sci. 15, 134–140 (2018).

    Article  Google Scholar 

  32. Roux, C. H. et al. Rheumatoid arthritis and spondyloarthropathies: geographical variations in prevalence in France. J. Rheumatol. 34, 117–122 (2007).

    PubMed  Google Scholar 

  33. Aho, K., Kaipiainen-Seppänen, O., Heliövaara, M. & Klaukka, T. Epidemiology of rheumatoid arthritis in Finland. Semin. Arthritis Rheum. 27, 325–334 (1998).

    Article  CAS  PubMed  Google Scholar 

  34. Grellmann, C. et al. Epidemiology and treatment of patients with rheumatoid arthritis, psoriatic arthritis and psoriasis in germany: a real-world evidence study. Adv. Ther. 38, 366–385 (2021).

    Article  PubMed  Google Scholar 

  35. Galushko, E. A. et al. Prevalence of rheumatoid arthritis in Russia (according to epidemiological findings). Ter. Arkh. 82, 9–14 (2010).

    CAS  PubMed  Google Scholar 

  36. Rossini, M. et al. Prevalence and incidence of rheumatoid arthritis in Italy. Rheumatol. Int. 34, 659–664 (2014).

    Article  PubMed  Google Scholar 

  37. Englund, M. et al. Prevalence and incidence of rheumatoid arthritis in southern Sweden 2008 and their relation to prescribed biologics. Rheumatology 49, 1563–1569 (2010).

    Article  PubMed  Google Scholar 

  38. Eriksson, J. K. et al. Incidence of rheumatoid arthritis in Sweden: a nationwide population-based assessment of incidence, its determinants, and treatment penetration. Arthritis Care Res. 65, 870–878 (2013).

    Article  Google Scholar 

  39. Kerola, A. M. et al. Incidence, sociodemographic factors and treatment penetration of rheumatoid arthritis and psoriatic arthritis in Norway. Semin. Arthritis Rheum. 51, 1081–1088 (2021).

    Article  PubMed  Google Scholar 

  40. Zlatković-Švenda, M. I., Stojanović, R. M., B. Šipetić-Grujičić, S. & Guillemin, F. Prevalence of rheumatoid arthritis in Serbia. Rheumatol. Int. 34, 649–658 (2014).

    Article  PubMed  Google Scholar 

  41. Adomaviciute, D. et al. Prevalence survey of rheumatoid arthritis and spondyloarthropathy in Lithuania. Scand. J. Rheumatol. 37, 113–119 (2008).

    Article  CAS  PubMed  Google Scholar 

  42. Pedersen, J. K., Svendsen, A. J. & Hørslev-Petersen, K. Prevalence of rheumatoid arthritis in the southern part of Denmark. Open Rheumatol. J. 5, 91–97 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Otsa, K. et al. The prevalence of rheumatoid arthritis in Estonia: an estimate based on rheumatology patients’ database. Rheumatol. Int. 33, 955–958 (2013).

    Article  CAS  PubMed  Google Scholar 

  44. Damjanović, V., Vasilj, I., Vlak, T. & Zelenika, D. Prevalence and risk factors of the rheumatoid arthritis in Herzegovina region in 2003–2005. Coll. Antropol. 33 (suppl. 2), 73–77 (2009).

    PubMed  Google Scholar 

  45. Tolentino Júnior, D. S., de Oliveira, C. M. & de Assis, E. M. Population-based study of 24 autoimmune diseases carried out in a Brazilian microregion. J. Epidem. Glob. Health 9, 243 (2019).

    Article  Google Scholar 

  46. Juárez, V. et al. Prevalence of musculoskeletal disorders and rheumatic diseases in an Argentinean indigenous Wichi community. Clin. Rheumatol. 40, 75–83 (2021).

    Article  PubMed  Google Scholar 

  47. Peláez-Ballestas, I. et al. Epidemiology and socioeconomic impact of the rheumatic diseases on indigenous people: an invisible syndemic public health problem. Ann. Rheum. Dis. 77, 1397–1404 (2018).

    Article  PubMed  Google Scholar 

  48. Peláez-Ballestas, I. et al. Epidemiology of the rheumatic diseases in Mexico. A study of 5 regions based on the COPCORD methodology. J. Rheumatol. Suppl. 86, 3–8 (2011).

    Article  PubMed  Google Scholar 

  49. Di, W. T. et al. Incidence and prevalence of rheumatoid arthritis in a health management organization in argentina: a 15-year study. J. Rheumatol. 43, 1306–1311 (2016).

    Article  PubMed  Google Scholar 

  50. da Rocha Castelar-Pinheiro, G. et al. The REAL study: a nationwide prospective study of rheumatoid arthritis in Brazil. Adv. Rheumatol. 58, 9 (2018).

    Article  PubMed  Google Scholar 

  51. Fernández-Ávila, D. G. et al. Current status of the rheumatologists’ workforce in Latin America: a PANLAR collaborative study. Clin. Rheumatol. 40, 2913–2920 (2021).

    Article  PubMed  Google Scholar 

  52. Blettery, M. et al. Rheumatoid arthritis in French Guiana: epidemiology and characteristics. Joint Bone Spine 86, 515–516 (2019).

    Article  PubMed  Google Scholar 

  53. Battafarano, D. F. et al. 2015 American college of rheumatology workforce study: supply and demand projections of adult rheumatology workforce, 2015–2030. Arthritis Care Res. 70, 617–626 (2018).

    Article  Google Scholar 

  54. Helmick, C. G. et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: part I. Arthritis Rheum. 58, 15–25 (2008).

    Article  PubMed  Google Scholar 

  55. Hunter, T. M. et al. Prevalence of rheumatoid arthritis in the United States adult population in healthcare claims databases, 2004–2014. Rheumatol. Int. 37, 1551–1557 (2017).

    Article  PubMed  Google Scholar 

  56. Crane, M. M. et al. Epidemiology and treatment of new-onset and established rheumatoid arthritis in an insured US population. Arthritis Care Res. 67, 1646–1655 (2015).

    Article  CAS  Google Scholar 

  57. Nair, B., Taylor-Gjevre, R., Wu, L., Jin, S. & Quail, J. M. Incidence and prevalence of rheumatoid arthritis in Saskatchewan, Canada: 2001–2014. BMC Rheumatol. 3, 28 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Widdifield, J. et al. The epidemiology of rheumatoid arthritis in Ontario, Canada. Arthritis Rheumatol. 66, 786–793 (2014).

    Article  PubMed  Google Scholar 

  59. Hitchon, C. A., Khan, S., Elias, B., Lix, L. M. & Peschken, C. A. Prevalence and incidence of rheumatoid arthritis in Canadian first nations and non–first nations people. J. Clin. Rheumatol. 26, 169–175 (2020).

    Article  PubMed  Google Scholar 

  60. Costenbader, K. H., Chang, S.-C., Laden, F., Puett, R. & Karlson, E. W. Geographic variation in rheumatoid arthritis incidence among women in the United States. Arch. Intern. Med. 168, 1664–1670 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Ferucci, E. D., Templin, D. W. & Lanier, A. P. Rheumatoid arthritis in American Indians and Alaska Natives: a review of the literature. Semin. Arthritis Rheum. 34, 662–667 (2005).

    Article  PubMed  Google Scholar 

  62. Harvey, J., Lotze, M., Stevens, M. B. & Jacobson, D. Rheumatoid arthritis in a Chippewa band. Arthritis Rheum. 24, 717–721 (1981).

    Article  CAS  PubMed  Google Scholar 

  63. Harvey, J. et al. Rheumatoid arthritis in a Chippewa band. II. Field study with clinical serologic and HLA-D correlations. J. Rheumatol. 10, 28–32 (1983).

    CAS  PubMed  Google Scholar 

  64. Australian Institute of Health and Welfare. Rheumatoid arthritis: impact of rheumatoid arthritis. Australian Government https://www.aihw.gov.au/reports/arthritis-other-musculoskeletal-conditions/rheumatoid-arthritis/contents/who-gets-rheumatoid-arthritis (2020).

  65. González-Chica, D. A., Vanlint, S., Hoon, E. & Stocks, N. Epidemiology of arthritis, chronic back pain, gout, osteoporosis, spondyloarthropathies and rheumatoid arthritis among 1.5 million patients in Australian general practice: NPS MedicineWise MedicineInsight dataset. BMC Musculoskelet. Disord. 19, 20 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Myasoedova, E., Davis, J., Matteson, E. L. & Crowson, C. S. Is the epidemiology of rheumatoid arthritis changing? Results from a population-based incidence study, 1985–2014. Ann. Rheum. Dis. 79, 440–444 (2020).

    Article  PubMed  Google Scholar 

  67. Bilano, V. et al. Global trends and projections for tobacco use, 1990–2025: an analysis of smoking indicators from the WHO comprehensive information systems for tobacco control. Lancet 385, 966–976 (2015).

    Article  PubMed  Google Scholar 

  68. Zilaout, H., Houba, R. & Kromhout, H. Temporal trends in respirable dust and respirable quartz concentrations within the European industrial minerals sector over a 15-year period (2002–2016). Occup. Env. Med. 77, 268–275 (2020).

    Article  Google Scholar 

  69. Peters, S. et al. Trends in exposure to respirable crystalline silica (1986–2014) in Australian mining. Am. J. Ind. Med. 60, 673–678 (2017).

    Article  PubMed  Google Scholar 

  70. CDC. Silicosis mortality trends and new exposures to respirable crystalline silica — United States, 2001–2010. CDC https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6405a1.htm (2015).

  71. Essouma, M. & Noubiap, J. J. N. Is air pollution a risk factor for rheumatoid arthritis? J. Inflamm. 12, 48 (2015).

    Article  Google Scholar 

  72. Maradit-Kremers, H. et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 52, 402–411 (2005).

    Article  PubMed  Google Scholar 

  73. Aviña-Zubieta, J. A. et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Care Res. 59, 1690–1697 (2008).

    Article  Google Scholar 

  74. Listing, J. et al. Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFα inhibitors and rituximab. Ann. Rheum. Dis. 74, 415–421 (2015).

    Article  CAS  PubMed  Google Scholar 

  75. Lard, L. R. et al. Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am. J. Med. 111, 446–451 (2001).

    Article  CAS  PubMed  Google Scholar 

  76. Yu, Z. et al. Implementation of treat-to-target for rheumatoid arthritis in the US: analysis of baseline data from a randomized controlled trial. Arthritis Care Res. 70, 801–806 (2018).

  77. Grigor, C. et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet 364, 263–269 (2004).

    Article  PubMed  Google Scholar 

  78. Safiri, S. et al. Prevalence, deaths, and disability-adjusted life years due to musculoskeletal disorders for 195 countries and territories 1990–2017. Arthritis Rheumatol. 73, 702–714 (2021).

    Article  CAS  PubMed  Google Scholar 

  79. Lacaille, D., Avina-Zubieta, J. A., Sayre, E. C. & Abrahamowicz, M. Improvement in 5-year mortality in incident rheumatoid arthritis compared with the general population — closing the mortality gap. Ann. Rheum. Dis. 76, 1057–1063 (2017).

    Article  PubMed  Google Scholar 

  80. Abhishek, A. et al. Rheumatoid arthritis and excess mortality: down but not out. A primary care cohort study using data from clinical practice research. Oxford Academic https://academic.oup.com/rheumatology/article/57/6/977/4904191 (2018).

  81. Zhang, Y. et al. Improved survival in rheumatoid arthritis: a general population-based cohort study. Ann. Rheum. Dis. 76, 408–413 (2017).

    Article  PubMed  Google Scholar 

  82. Provan, S. A. et al. Trends in all-cause and cardiovascular mortality in patients with incident rheumatoid arthritis: a 20-year follow-up matched case–cohort study. Rheumatology 59, 505–512 (2020).

    PubMed  Google Scholar 

  83. Myasoedova, E. et al. Improved incidence of cardiovascular disease in patients with incident rheumatoid arthritis in the 2000s: a population-based cohort study. J. Rheumatol. 48, 1379–1387 (2021).

  84. Widdifield, J. et al. Trends in excess mortality among patients with rheumatoid arthritis in Ontario, Canada. Arthritis Care Res. 67, 1047–1053 (2015).

    Article  Google Scholar 

  85. van den Hoek, J. et al. Mortality in patients with rheumatoid arthritis: a 15-year prospective cohort study. Rheumatol. Int. 37, 487–493 (2017).

    Article  PubMed  Google Scholar 

  86. Holmqvist, M., Ljung, L. & Askling, J. Mortality following new-onset rheumatoid arthritis: has modern rheumatology had an impact? Ann. Rheum. Dis. 77, 85–91 (2018).

    Article  PubMed  Google Scholar 

  87. Humphreys, J. H. et al. Mortality trends in patients with early rheumatoid arthritis over 20 years: results from the Norfolk Arthritis Register. Arthritis Care Res. 66, 1296–1301 (2014).

    Article  CAS  Google Scholar 

  88. Gao, J. et al. Twenty-year changes in mortality rates and underlying causes of death in patients with rheumatoid arthritis-associated interstitial lung disease. Scand. J. Rheumatol. 50, 360–364 (2021).

    Article  CAS  PubMed  Google Scholar 

  89. Jeganathan, N., Nguyen, E. & Sathananthan, M. Rheumatoid arthritis and associated-interstitial lung disease: mortality rates and trends. Ann. Am. Thorac. Soc. https://doi.org/10.1513/AnnalsATS.202102-115OC (2021).

    Article  PubMed  Google Scholar 

  90. Samhouri, B. F. et al. The incidence, risk factors, and mortality of clinical and subclinical rheumatoid arthritis-associated interstitial lung disease: a population-based cohort. Arthritis Care Res. https://doi.org/10.1002/acr.24856 (2022).

    Article  Google Scholar 

  91. Minichiello, E., Semerano, L. & Boissier, M.-C. Time trends in the incidence, prevalence, and severity of rheumatoid arthritis: a systematic literature review. Joint Bone Spine 83, 625–630 (2016).

    Article  PubMed  Google Scholar 

  92. Turesson, C., O’Fallon, W. M., Crowson, C. S., Gabriel, S. E. & Matteson, E. L. Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann. Rheum. Dis. 62, 722–727 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Watts, R. A., Mooney, J., Lane, S. E. & Scott, D. G. I. Rheumatoid vasculitis: becoming extinct? Rheumatology 43, 920–923 (2004).

    Article  CAS  PubMed  Google Scholar 

  94. Kaipiainen-Seppänen, O., Myllykangas-Luosujärvi, R., Lampainen, E. & Ikäheimo, R. Intensive treatment of rheumatoid arthritis reduces need for dialysis due to secondary amyloidosis. Scand. J. Rheumatol. 29, 232–235 (2000).

    Article  PubMed  Google Scholar 

  95. Andersson, M. L. E., Forslind, K. & Hafström, I. Patients with early rheumatoid arthritis in the 2000s have equal disability and pain despite less disease activity compared with the 1990s: data from the BARFOT study over 8 years. J. Rheumatol. 44, 723–731 (2017).

    Article  CAS  PubMed  Google Scholar 

  96. Myasoedova, E., Davis, J. M., Achenbach, S. J., Matteson, E. L. & Crowson, C. S. Trends in prevalence of functional disability in rheumatoid arthritis compared with the general population. Mayo Clin. Proc. 94, 1035–1039 (2019).

    Article  PubMed  Google Scholar 

  97. Burn, E. et al. Lifetime risk of knee and hip replacement following a diagnosis of RA: findings from a cohort of 13961 patients from England. Rheumatology 58, 1950–1954 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  98. Young, B. L. et al. Trends in joint replacement surgery in patients with rheumatoid arthritis. J. Rheumatol. 45, 158–164 (2018).

    Article  PubMed  Google Scholar 

  99. Nystad, T. W. et al. Reduction in orthopaedic surgery in patients with rheumatoid arthritis: a Norwegian register-based study. Scand. J. Rheumatol. 45, 1–7 (2016).

    Article  CAS  PubMed  Google Scholar 

  100. Richter, M. D., Crowson, C. S., Matteson, E. L. & Makol, A. Orthopedic surgery among patients with rheumatoid arthritis: a population-based study to identify risk factors, sex differences, and time trends. Arthritis Care Res. 70, 1546–1550 (2018).

    Article  CAS  Google Scholar 

  101. Nikiphorou, E. et al. Hand and foot surgery rates in rheumatoid arthritis have declined from 1986 to 2011, but large-joint replacement rates remain unchanged: results from two UK inception cohorts. Arthritis Rheumatol. 66, 1081–1089 (2014).

    Article  PubMed  Google Scholar 

  102. Gomes, R. K. S. et al. Impact of rheumatoid arthritis in the public health system in Santa Catarina, Brazil: a descriptive and temporal trend analysis from 1996 to 2009. Rev. Bras. Reumatol. 57, 204–209 (2017).

    Article  Google Scholar 

  103. Cram, P. et al. Long-term trends in hip arthroplasty use and volume. J. Arthroplast. 27, 278–285.e2 (2012).

    Article  Google Scholar 

  104. Cram, P. et al. Total knee arthroplasty volume, utilization, and outcomes among medicare beneficiaries, 1991–2010. JAMA 308, 1227 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Galarza-Delgado, D. A. et al. Prevalence of comorbidities in Mexican mestizo patients with rheumatoid arthritis. Rheumatol. Int. 37, 1507–1511 (2017).

    Article  PubMed  Google Scholar 

  106. Cardiel, M. H. et al. Treatment of early rheumatoid arthritis in a multinational inception cohort of latin american patients: the GLADAR experience. J. Clin. Rheumatol. 18, 327–335 (2012).

    Article  PubMed  Google Scholar 

  107. Castillo-Cañón, J. C. et al. Rheumatoid arthritis in Colombia: a clinical profile and prevalence from a national registry. Clin. Rheumatol. 40, 3565–3573 (2021).

    Article  PubMed  Google Scholar 

  108. Barragán-Martínez, C. et al. Gender differences in Latin-American patients with rheumatoid arthritis. Gend. Med. 9, 490–510.e5 (2012).

    Article  PubMed  Google Scholar 

  109. Alpízar-Rodríguez, D., Pluchino, N., Canny, G., Gabay, C. & Finckh, A. The role of female hormonal factors in the development of rheumatoid arthritis. Rheumatology 56, 1254–1263 (2017).

    Article  PubMed  Google Scholar 

  110. Bengtsson, C. et al. Association between menopausal factors and the risk of seronegative and seropositive rheumatoid arthritis: results from the Nurses’ Health Studies. Arthritis Care Res. 69, 1676–1684 (2017).

    Article  CAS  Google Scholar 

  111. Beydoun, H. A., el-Amin, R., McNeal, M., Perry, C. & Archer, D. F. Reproductive history and postmenopausal rheumatoid arthritis among women 60 years or older: Third National Health and Nutrition Examination Survey. Menopause 20, 930–935 (2013).

    Article  PubMed  Google Scholar 

  112. Chen, J. Y. & Ballou, S. P. The effect of antiestrogen agents on risk of autoimmune disorders in patients with breast cancer. J. Rheumatol. 42, 55–59 (2015).

    Article  PubMed  Google Scholar 

  113. Pladevall-Vila, M. et al. Controversy of oral contraceptives and risk of rheumatoid arthritis: meta-analysis of conflicting studies and review of conflicting meta-analyses with special emphasis on analysis of heterogeneity. Am. J. Epidemiol. 144, 1–14 (1996).

    Article  CAS  PubMed  Google Scholar 

  114. Orellana, C. et al. Oral contraceptives, breastfeeding and the risk of developing rheumatoid arthritis: results from the Swedish EIRA study. Ann. Rheum. Dis. 76, 1845–1852 (2017).

    Article  CAS  PubMed  Google Scholar 

  115. Orellana, C. et al. Postmenopausal hormone therapy and the risk of rheumatoid arthritis: results from the Swedish EIRA population-based case-control study. Eur. J. Epidemiol. 30, 449–457 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Guthrie, K. A., Dugowson, C. E., Voigt, L. F., Koepsell, T. D. & Nelson, J. L. Does pregnancy provide vaccine-like protection against rheumatoid arthritis? Arthritis Rheum. 62, 1842–1848 (2010).

    PubMed  PubMed Central  Google Scholar 

  117. Wallenius, M. et al. Postpartum onset of rheumatoid arthritis and other chronic arthritides: results from a patient register linked to a medical birth registry. Ann. Rheum. Dis. 69, 332–336 (2010).

    Article  CAS  PubMed  Google Scholar 

  118. Peschken, C. A. et al. Pregnancy and the risk of rheumatoid arthritis in a highly predisposed North American native population. J. Rheumatol. 39, 2253–2260 (2012).

    Article  PubMed  Google Scholar 

  119. Chen, H., Wang, J., Zhou, W., Yin, H. & Wang, M. Breastfeeding and risk of rheumatoid arthritis: a systematic review and metaanalysis. J. Rheumatol. 42, 1563–1569 (2015).

    Article  PubMed  Google Scholar 

  120. Adab, P. et al. Breastfeeding practice, oral contraceptive use and risk of rheumatoid arthritis among Chinese women: the Guangzhou Biobank Cohort Study. Rheumatology 53, 860–866 (2014).

    Article  PubMed  Google Scholar 

  121. Karlson, E. W., Mandl, L. A., Hankinson, S. E. & Grodstein, F. Do breast-feeding and other reproductive factors influence future risk of rheumatoid arthritis? Results from the Nurses’ Health Study. Arthritis Rheum. 50, 3458–3467 (2004).

    Article  PubMed  Google Scholar 

  122. Sparks, J. A. et al. Contributions of familial rheumatoid arthritis or lupus and environmental factors to risk of rheumatoid arthritis in women: a prospective cohort study: familial and environmental risk of RA. Arthritis Care Res. 66, 1438–1446 (2014).

    Article  Google Scholar 

  123. Puska, P., Vartiainen, E., Tuomilehto, J., Salomaa, V. & Nissinen, A. Changes in premature deaths in Finland: successful long-term prevention of cardiovascular diseases. Bull. World Health Organ. 76, 419–425 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Holers, V. M. et al. Rheumatoid arthritis and the mucosal origins hypothesis: protection turns to destruction. Nat. Rev. Rheumatol. 14, 542–557 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Willis, V. C. et al. Sputum autoantibodies in patients with established rheumatoid arthritis and subjects at risk of future clinically apparent disease. Arthritis Rheum. 65, 2545–2554 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Demoruelle, M. K. et al. Antibody responses to citrullinated and noncitrullinated antigens in the sputum of subjects with rheumatoid arthritis and subjects at risk for development of rheumatoid arthritis. Arthritis Rheumatol. 70, 516–527 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Reynisdottir, G. et al. Structural changes and antibody enrichment in the lungs are early features of anti–citrullinated protein antibody–positive rheumatoid arthritis. Arthritis Rheumatol. 66, 31–39 (2014).

    Article  CAS  PubMed  Google Scholar 

  128. Deane, K. D. et al. Genetic and environmental risk factors for rheumatoid arthritis. Best. Pract. Res. Clin. Rheumatol. 31, 3–18 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  129. Costenbader, K. H., Feskanich, D., Mandl, L. A. & Karlson, E. W. Smoking intensity, duration, and cessation, and the risk of rheumatoid arthritis in women. Am. J. Med. 119, 503.e1–503.e9 (2006).

    Article  Google Scholar 

  130. Kim, K. et al. Interactions between amino acid–defined major histocompatibility complex class II variants and smoking in seropositive rheumatoid arthritis. Arthritis Rheumatol. 67, 2611–2623 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  131. Pedersen, M. et al. Strong combined gene–environment effects in anti–cyclic citrullinated peptide–positive rheumatoid arthritis: a nationwide case–control study in Denmark. Arthritis Rheum. 56, 1446–1453 (2007).

    Article  PubMed  Google Scholar 

  132. Wouters, F. et al. Determining in which pre-arthritis stage HLA-shared epitope alleles and smoking exert their effect on the development of rheumatoid arthritis. Ann. Rheum. Dis. 81, 48–55 (2022).

    Article  CAS  PubMed  Google Scholar 

  133. Hart Jaime, E., Laden, F., Puett Robin, C., Costenbader Karen, H. & Karlson Elizabeth, W. Exposure to traffic pollution and increased risk of rheumatoid arthritis. Environ. Health Perspect. 117, 1065–1069 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. De, R. A. J., Koehoorn, M., Tamburic, L., Davies, H. W. & Brauer, M. Proximity to traffic, ambient air pollution, and community noise in relation to incident rheumatoid arthritis. Environ. Health Perspect. 122, 1075–1080 (2014).

    Article  Google Scholar 

  135. Chang, K.-H. et al. Air pollution exposure increases the risk of rheumatoid arthritis: a longitudinal and nationwide study. Environ. Int. 94, 495–499 (2016).

    Article  CAS  PubMed  Google Scholar 

  136. Miller-Archie, S. A. et al. Systemic autoimmune disease among adults exposed to the september 11, 2001 terrorist attack. Arthritis Rheumatol. 72, 849–859 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  137. Too, C. L. et al. Occupational exposure to textile dust increases the risk of rheumatoid arthritis: results from a Malaysian population-based case–control study. Ann. Rheum. Dis. 75, 997–1002 (2016).

    Article  CAS  PubMed  Google Scholar 

  138. Stolt, P. et al. Silica exposure among male current smokers is associated with a high risk of developing ACPA-positive rheumatoid arthritis. Ann. Rheum. Dis. 69, 1072–1076 (2010).

    Article  CAS  PubMed  Google Scholar 

  139. Hart, J. E. et al. Ambient air pollution exposures and risk of rheumatoid arthritis. Arthritis Care Res. 65, 1190–1196 (2013).

    Article  CAS  Google Scholar 

  140. Parks, C. G., Conrad, K. & Cooper, G. S. Occupational exposure to crystalline silica and autoimmune disease. Environ. Health Perspect. 107 (suppl. 5), 793–802 (1999).

    PubMed  PubMed Central  Google Scholar 

  141. Schmajuk, G., Trupin, L., Yelin, E. & Blanc, P. D. Prevalence of arthritis and rheumatoid arthritis in coal mining counties of the United States. Arthritis Care Res. 71, 1209–1215 (2019).

    Article  CAS  Google Scholar 

  142. Turner, S. Rheumatoid arthritis in workers exposed to silica in the pottery industry. Occup. Environ. Med. 57, 443–447 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Yamamoto, S. S. et al. Household air pollution and arthritis in low-and middle-income countries: cross-sectional evidence from the World Health Organization’s study on global ageing and adult health. PLoS ONE 14, e0226738 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Bonjour, S. et al. Solid fuel use for household cooking: country and regional estimates for 1980–2010. Environ. Health Perspect. 121, 784–790 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  145. Charoenngam, N. et al. Patients with asthma have a higher risk of rheumatoid arthritis: a systematic review and meta-analysis. Semin. Arthritis Rheum. 50, 968–976 (2020).

    Article  PubMed  Google Scholar 

  146. Ford, J. A. et al. Asthma, chronic obstructive pulmonary disease, and subsequent risk for incident rheumatoid arthritis among women: a prospective cohort study. Arthritis Rheumatol. https://doi.org/10.1002/art.41194 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  147. Friedlander, H. M. et al. Obstructive lung diseases and risk of rheumatoid arthritis. Expert. Rev. Clin. Immunol. 16, 37–50 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Hu, Y. et al. Long-term dietary quality and risk of developing rheumatoid arthritis in women. Ann. Rheum. Dis. 76, 1357–1364 (2017).

    Article  CAS  PubMed  Google Scholar 

  149. Hu, Y. et al. Mediterranean diet and incidence of rheumatoid arthritis in women. Arthritis Care Res. 67, 597–606 (2015).

    Article  Google Scholar 

  150. Johansson, K., Askling, J., Alfredsson, L. & Di Giuseppe, D. (EIRA study group). Mediterranean diet and risk of rheumatoid arthritis: a population-based case-control study. Arthritis Res. Ther. 20, 175 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Nguyen, Y. et al. Mediterranean diet and risk of rheumatoid arthritis: findings from the French E3N-EPIC cohort study. Arthritis Rheumatol. 73, 69–77 (2021).

    Article  PubMed  Google Scholar 

  152. Sparks, J. A. et al. Inflammatory dietary pattern and risk of developing rheumatoid arthritis in women. Clin. Rheumatol. 38, 243–250 (2019).

    Article  PubMed  Google Scholar 

  153. Pattison, D. J. et al. Dietary risk factors for the development of inflammatory polyarthritis: evidence for a role of high level of red meat consumption. Arthritis Rheum. 50, 3804–3812 (2004).

    Article  PubMed  Google Scholar 

  154. Benito-Garcia, E., Feskanich, D., Hu, F. B., Mandl, L. A. & Karlson, E. W. Protein, iron, and meat consumption and risk for rheumatoid arthritis: a prospective cohort study. Arthritis Res. Ther. 9, R16 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  155. Sundström, B., Ljung, L. & Di Giuseppe, D. Consumption of meat and dairy products is not associated with the risk for rheumatoid arthritis among women: a population-based cohort study. Nutrients 11, 2825 (2019).

    Article  PubMed Central  Google Scholar 

  156. Hu, Y. et al. Sugar-sweetened soda consumption and risk of developing rheumatoid arthritis in women. Am. J. Clin. Nutr. 100, 959–967 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. DeChristopher, L. R., Uribarri, J. & Tucker, K. L. Intake of high-fructose corn syrup sweetened soft drinks, fruit drinks and apple juice is associated with prevalent arthritis in US adults, aged 20–30 years. Nutr. Diabetes 6, e199 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Källberg, H. et al. Alcohol consumption is associated with decreased risk of rheumatoid arthritis: results from two Scandinavian case–control studies. Ann. Rheum. Dis. 68, 222–227 (2009).

    Article  PubMed  Google Scholar 

  159. Scott, I. C. et al. The protective effect of alcohol on developing rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology 52, 856–867 (2013).

    Article  CAS  PubMed  Google Scholar 

  160. Sundström, B., Johansson, I. & Rantapää-Dahlqvist, S. Diet and alcohol as risk factors for rheumatoid arthritis: a nested case–control study. Rheumatol. Int. 35, 533–539 (2015).

    Article  PubMed  Google Scholar 

  161. Salgado, E., Bes-Rastrollo, M., de Irala, J., Carmona, L. & Gómez-Reino, J. J. High sodium intake is associated with self-reported rheumatoid arthritis: a cross sectional and case control analysis within the SUN cohort. Medicine 94, e0924 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Sundström, B., Johansson, I. & Rantapää-Dahlqvist, S. Interaction between dietary sodium and smoking increases the risk for rheumatoid arthritis: results from a nested case–control study. Rheumatology 54, 487–493 (2015).

    Article  PubMed  Google Scholar 

  163. Lu, B. et al. Being overweight or obese and risk of developing rheumatoid arthritis among women: a prospective cohort study. Ann. Rheum. Dis. 73, 1914–1922 (2014).

    Article  PubMed  Google Scholar 

  164. Wesley, A. et al. Association between body mass index and anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis: results from a population-based case-control study. Arthritis Care Res. 65, 107–112 (2013).

    Article  Google Scholar 

  165. Linauskas, A. et al. Body fat percentage, waist circumference, and obesity as risk factors for rheumatoid arthritis: a Danish cohort study. Arthritis Care Res. 71, 777–786 (2019).

    Article  Google Scholar 

  166. de Hair, M. J. H. et al. Smoking and overweight determine the likelihood of developing rheumatoid arthritis. Ann. Rheum. Dis. 72, 1654–1658 (2013).

    Article  PubMed  Google Scholar 

  167. Turesson, C., Bergström, U., Pikwer, M., Nilsson, J.-Å. & Jacobsson, L. T. H. A high body mass index is associated with reduced risk of rheumatoid arthritis in men, but not in women. Rheumatology 55, 307–314 (2016).

    Article  PubMed  Google Scholar 

  168. Pedersen, M. et al. Diet and risk of rheumatoid arthritis in a prospective cohort. J. Rheumatol. 32, 1249–1252 (2005).

    PubMed  Google Scholar 

  169. Rosell, M. et al. Dietary fish and fish oil and the risk of rheumatoid arthritis. Epidemiology 20, 896–901 (2009).

    Article  PubMed  Google Scholar 

  170. Giuseppe, D. D., Wallin, A., Bottai, M., Askling, J. & Wolk, A. Long-term intake of dietary long-chain n-3 polyunsaturated fatty acids and risk of rheumatoid arthritis: a prospective cohort study of women. Ann. Rheum. Dis. 73, 1949–1953 (2014).

    Article  PubMed  Google Scholar 

  171. Sparks, J. A. et al. Association of fish intake and smoking with risk of rheumatoid arthritis and age of onset: a prospective cohort study. BMC Musculoskelet. Disord. 20, 2 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  172. Gan, R. W. et al. Omega-3 fatty acids are associated with a lower prevalence of autoantibodies in shared epitope-positive subjects at risk for rheumatoid arthritis. Ann. Rheum. Dis. 76, 147–152 (2017).

    Article  PubMed  Google Scholar 

  173. Gan, R. W. et al. Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study. Rheumatology 55, 367–376 (2016).

    Article  CAS  PubMed  Google Scholar 

  174. Hahn, J. et al. Vitamin D and marine n-3 fatty acid supplementation and prevention of autoimmune disease in the VITAL randomized controlled trial. ACR Meet. Abstr. https://acrabstracts.org/abstract/vitamin-d-and-marine-n-3-fatty-acid-supplementation-and-prevention-of-autoimmune-disease-in-the-vital-randomized-controlled-trial/ (2021).

  175. Hahn, J. et al. Association of healthy lifestyle behaviors and the risk of developing rheumatoid arthritis among women. Arthritis Care Res. https://doi.org/10.1002/acr.24862 (2022).

    Article  Google Scholar 

  176. Koller-Smith, L. et al. Rheumatoid arthritis is a preventable disease: 11 ways to reduce your patients’ risk. Intern. Med. J. https://doi.org/10.1111/imj.15537 (2021).

    Article  Google Scholar 

  177. Vadell, A. K. E. et al. Anti-inflammatory diet in rheumatoid arthritis (ADIRA) — a randomized, controlled crossover trial indicating effects on disease activity. Am. J. Clin. Nutr. 111, 1203–1213 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  178. Bustamante, M. F. et al. Design of an anti-inflammatory diet (ITIS diet) for patients with rheumatoid arthritis. Contemp. Clin. Trials Commun. 17, 100524 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  179. Azizov, V. et al. Ethanol consumption inhibits TFH cell responses and the development of autoimmune arthritis. Nat. Commun. 11, 1998 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Maeda, Y. et al. Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine. Arthritis Rheumatol. 68, 2646–2661 (2016).

    Article  CAS  PubMed  Google Scholar 

  181. Scher, J. U. et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife 2, e01202 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  182. Jeong, Y. et al. Gut microbial composition and function are altered in patients with early rheumatoid arthritis. J. Clin. Med. 8, 693 (2019).

    Article  CAS  PubMed Central  Google Scholar 

  183. Kishikawa, T. et al. Metagenome-wide association study of gut microbiome revealed novel aetiology of rheumatoid arthritis in the Japanese population. Ann. Rheum. Dis. 79, 103–111 (2020).

    Article  CAS  PubMed  Google Scholar 

  184. Zhang, X. et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat. Med. 21, 895–905 (2015).

    Article  CAS  PubMed  Google Scholar 

  185. Chen, J. et al. An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med. 8, 43 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  186. Mena-Vázquez, N. et al. Expansion of rare and harmful lineages is associated with established rheumatoid arthritis. J. Clin. Med. 9, 1044 (2020).

    Article  PubMed Central  Google Scholar 

  187. Alpizar-Rodriguez, D. et al. Prevotella copri in individuals at risk for rheumatoid arthritis. Ann. Rheum. Dis. 78, 590–593 (2019).

    Article  CAS  PubMed  Google Scholar 

  188. Tong, Y., Zhao, Y., Liu, Y. & Luo, Y. Gut microbiota dysbiosis in the high-risk individual for RA triggers the mucosal immunity perturbation and promotes rheumatoid arthritis development. Ann. Rheum. Dis. 79, 11–12 (2020).

    Article  Google Scholar 

  189. Palm, N. W. et al. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell 158, 1000–1010 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Gacesa, R. et al. Environmental factors shaping the gut microbiome in a Dutch population. Nature 604, 732–739 (2022).

    Article  CAS  PubMed  Google Scholar 

  191. Nguyen, Y. et al. Chronic diarrhoea and risk of rheumatoid arthritis: findings from the French E3N-EPIC cohort study. Rheumatology https://doi.org/10.1093/rheumatology/keaa133 (2020).

    Article  PubMed  Google Scholar 

  192. Chen, B. et al. Variations in oral microbiome profiles in rheumatoid arthritis and osteoarthritis with potential biomarkers for arthritis screening. Sci. Rep. 8, 17126 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  193. Demmer, R. T., Molitor, J. A., Jacobs, D. R. & Michalowicz, B. S. Periodontal disease, tooth loss and incident rheumatoid arthritis: results from the First National Health and Nutrition Examination Survey and its epidemiological follow-up study. J. Clin. Periodontol. 38, 998–1006 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  194. Loutan, L. et al. Periodontal status correlates with anti-citrullinated protein antibodies in first-degree relatives of individuals with rheumatoid arthritis. J. Clin. Periodontol. 46, 690–698 (2019).

    CAS  PubMed  Google Scholar 

  195. Manoil, D. et al. Associations between serum antibodies to periodontal pathogens and preclinical phases of rheumatoid arthritis. Rheumatology https://doi.org/10.1093/rheumatology/keab097 (2021).

    Article  PubMed  Google Scholar 

  196. Lundberg, K., Wegner, N., Yucel-Lindberg, T. & Venables, P. J. Periodontitis in RA — the citrullinated enolase connection. Nat. Rev. Rheumatol. 6, 727–730 (2010).

    Article  CAS  PubMed  Google Scholar 

  197. Konig, M. F. et al. Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci. Transl. Med. 8, 369ra176–369ra176 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  198. Moentadj, R. et al. Streptococcus species enriched in the oral cavity of patients with RA are a source of peptidoglycan-polysaccharide polymers that can induce arthritis in mice. Ann. Rheum. Dis. 80, 573–581 (2021).

    Article  CAS  PubMed  Google Scholar 

  199. Smolen, J. S. et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann. Rheum. Dis. 69, 631–637 (2010).

    Article  PubMed  Google Scholar 

  200. Thomas, K. et al. Treatment patterns and achievement of the treat-to-target goals in a real-life rheumatoid arthritis patient cohort: data from 1317 patients. Ther. Adv. Musculoskelet. 12, 1759720X20937132 (2020).

    CAS  Google Scholar 

  201. Kaneko, Y. et al. Obstacles to the implementation of the treat-to-target strategy for rheumatoid arthritis in clinical practice in Japan. Mod. Rheumatol. 25, 43–49 (2015).

    Article  PubMed  Google Scholar 

  202. Aga, A.-B. et al. Time trends in disease activity, response and remission rates in rheumatoid arthritis during the past decade: results from the NOR-DMARD study 2000–2010. Ann. Rheum. Dis. 74, 381–388 (2015).

    Article  CAS  PubMed  Google Scholar 

  203. Hyrich, K. L., Watson, K. D., Lunt, M. & Symmons, D. P. M. Changes in disease characteristics and response rates among patients in the United Kingdom starting anti-tumour necrosis factor therapy for rheumatoid arthritis between 2001 and 2008. Rheumatology 50, 117–123 (2011).

    Article  CAS  PubMed  Google Scholar 

  204. Sánchez-Piedra, C. et al. Changes in the use patterns of bDMARDs in patients with rheumatic diseases over the past 13 years. Sci. Rep. 11, 15051 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  205. Favalli, E. G., Becciolini, A. & Meroni, P. L. Change over time in the pattern of clinical response to first-line biologic drugs in patients with rheumatoid arthritis: observational data in a real-life setting. J. Rheumatol. 44, 262–263 (2017).

    Article  PubMed  Google Scholar 

  206. Simard, J. F. et al. Ten years with biologics: to whom do data on effectiveness and safety apply? Rheumatology 50, 204–213 (2011).

    Article  PubMed  Google Scholar 

  207. Hitchon, C. A. et al. Perceptions and challenges experienced by African physicians when prescribing methotrexate for rheumatic disease: an exploratory study. ACR Open Rheumatol. 3, 522–530 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  208. Contreras-Yáñez, I. et al. Association of significant risk perception with the use of complementary and alternative medicine: a cross-sectional study in Hispanic patients with rheumatoid arthritis. PLoS ONE 15, e0237504 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  209. Tarr, G., Makda, M., Musenge, E. & Tikly, M. Effect of human immunodeficiency virus infection on disease activity in rheumatoid arthritis: a retrospective study in South Africans. J. Rheumatol. 41, 1645–1649 (2014).

    Article  PubMed  Google Scholar 

  210. Pettipher, C. & Benitha, R. Tuberculosis in biologic users for rheumatic diseases: results from the South African Biologics Registry (SABIO). Ann. Rheum. Dis. 79, 292–299 (2020).

    Article  CAS  PubMed  Google Scholar 

  211. du Toit, T. et al. Incident tuberculosis disease in patients receiving biologic therapies in the Western Cape, South Africa from 2007 to 2018. BMC Infect. Dis. 20, 900 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  212. Adelowo, O. O., Olisa, O., Asekhame, O. T. & Ojo, O. Biotherapies in medical practice: a review and the Nigerian experience. West. Afr. J. Med. 38, 486–493 (2021).

    CAS  PubMed  Google Scholar 

  213. Bouajina, E., Zakraoui, L., Kchir, M., Kochbati, S. & Baklouti, S. Safety and efficacy of tocilizumab as monotherapy or in combination with methotrexate in Tunisian patients with active rheumatoid arthritis and inadequate response to disease-modifying anti-rheumatic drugs in conditions close to clinical practice. Clin. Rheumatol. 39, 1449–1455 (2020).

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank L. Koller-Smith, L. March, E. Park, Y.-C. Kwon, K. Kim and S.-K. Cho for helpful discussions in the preparation of this manuscript. A.F. is supported in part by the Swiss National Science Foundation (grants 310030E_205559/1 and 320030_192471/1). S.-C.B. is supported in part by the Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Education (grant NRF-2021R1A6A1A03038899). R.T. is supported by Arthritis Queensland and the National Health and Medical Research Council of Australia (grant 2008287).

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Authors and Affiliations

  1. Division of Rheumatology, Department of Medicine, Geneva University Hospital (HUG), Geneva, Switzerland

    Axel Finckh, Benoît Gilbert & Kim Lauper

  2. Division of Rheumatology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa

    Bridget Hodkinson

  3. Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Hanyang University Institute for Rheumatology and Hanyang University Institute of Bioscience and Biotechnology, Seoul, Republic of Korea

    Sang-Cheol Bae

  4. The University of Queensland Diamantina Institute, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia

    Ranjeny Thomas

  5. University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Kevin D. Deane

  6. Research Unit, Colegio Mexicano de Reumatología, Mexico City, Mexico

    Deshiré Alpizar-Rodriguez

  7. Centre for Epidemiology versus Arthritis, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK

    Kim Lauper

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A.F. received funding from Abbvie, Bristol Myers Squibb, Galapagos, and Pfizer to the Geneva University Hospital, and consultancy or honoraria from Abbvie, Bristol Myers Squibb, Eli-Lilly, MSD and Pfizer. R.T. received funding from Janssen Biotech to Uniquest (the commercialization company of the University of Queensland), consultancy or honoraria from Bristol Myers Squibb, Abbvie, Janssen, Merck, CSL, Viela Bio and Sandoz, and is a named inventor on patent 9,017,697 B2, relating to compositions and methods for modulating immune responses. K.D.D. received funding for consultancy from Inova Diagnostics, Bristol Myers Squibb and Janssen. D.A.R. is a scientific adviser for GlaxoSmithKline Mexico, unrelated to the topic of this manuscript. K.L. received consultancy or honoraria from Celltrion, Pfizer, Viatris and Galapagos. The other authors declare no competing interests.

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Finckh, A., Gilbert, B., Hodkinson, B. et al. Global epidemiology of rheumatoid arthritis. Nat Rev Rheumatol 18, 591–602 (2022). https://doi.org/10.1038/s41584-022-00827-y

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