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Is the prevention of rheumatoid arthritis possible?

  • Perspectives in Rheumatology
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Abstract

Preclinical phases of rheumatoid arthritis (RA) have been described, genetic and environmental risk factors for RA development have been identified, and several biomarkers of RA have been detected long before the clinical onset of the disease; all of which have opened the possibility for preventive interventions. Several studies are currently exploring pharmacological and non-pharmacological interventions to prevent the development of RA. We will review the evidence for prevention of RA and discuss key challenges for preventive interventions, including identification of the adequate target population, the risks of applying potentially harmful and expensive therapies to asymptomatic at-risk individuals, and the importance of taking into account the preferences of individuals at risk regarding preventive treatment options.

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References

  1. Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, McInnes IB, Solomon DH, Strand V, Yamamoto K (2018) Rheumatoid arthritis. Nat Rev Dis Primers 4:18001. https://doi.org/10.1038/nrdp.2018.1

    Article  PubMed  Google Scholar 

  2. Safiri S, Kolahi AA, Hoy D, Smith E, Bettampadi D, Mansournia MA, Almasi-Hashiani A, Ashrafi-Asgarabad A, Moradi-Lakeh M, Qorbani M, Collins G, Woolf AD, March L, Cross M (2019) 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(11):1463–1471. https://doi.org/10.1136/annrheumdis-2019-215920

    Article  PubMed  Google Scholar 

  3. Goemaere S, Ackerman C, Goethals K, De Keyser F, Van der Straeten C, Verbruggen G, Mielants H, Veys EM (1990) Onset of symptoms of rheumatoid arthritis in relation to age, sex and menopausal transition. J Rheumatol 17(12):1620–1622

    CAS  PubMed  Google Scholar 

  4. Tedeschi SK, Bermas B, Costenbader KH (2013) Sexual disparities in the incidence and course of SLE and RA. Clin Immunol 149(2):211–218. https://doi.org/10.1016/j.clim.2013.03.003

    Article  CAS  PubMed  Google Scholar 

  5. Cross M, Smith E, Hoy D, Carmona L, Wolfe F, Vos T, Williams B, Gabriel S, Lassere M, Johns N, Buchbinder R, Woolf A, March L (2014) The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 73(7):1316–1322. https://doi.org/10.1136/annrheumdis-2013-204627

    Article  PubMed  Google Scholar 

  6. Klareskog L, Stolt P, Lundberg K, Kallberg H, Bengtsson C, Grunewald J, Ronnelid J, Harris HE, Ulfgren AK, Rantapaa-Dahlqvist S, Eklund A, Padyukov L, Alfredsson L (2006) A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 54(1):38–46. https://doi.org/10.1002/art.21575

    Article  CAS  PubMed  Google Scholar 

  7. Sparks JA, Chen CY, Hiraki LT, Malspeis S, Costenbader KH, Karlson EW (2014) Contributions of familial rheumatoid arthritis or lupus and environmental factors to risk of rheumatoid arthritis in women: a prospective cohort study. Arthritis Care Res 66(10):1438–1446. https://doi.org/10.1002/acr.22366

    Article  Google Scholar 

  8. Svendsen AJ, Holm NV, Kyvik K, Petersen PH, Junker P (2002) Relative importance of genetic effects in rheumatoid arthritis: historical cohort study of Danish nationwide twin population. BMJ 324(7332):264–266

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hensvold AH, Magnusson PK, Joshua V, Hansson M, Israelsson L, Ferreira R, Jakobsson PJ, Holmdahl R, Hammarstrom L, Malmstrom V, Askling J, Klareskog L, Catrina AI (2015) Environmental and genetic factors in the development of anticitrullinated protein antibodies (ACPAs) and ACPA-positive rheumatoid arthritis: an epidemiological investigation in twins. Ann Rheum Dis 74(2):375–380. https://doi.org/10.1136/annrheumdis-2013-203947

    Article  PubMed  Google Scholar 

  10. Zaccardelli A, Friedlander HM, Ford JA, Sparks JA (2019) Potential of lifestyle changes for reducing the risk of developing rheumatoid arthritis: is an ounce of prevention worth a pound of cure? Clin Ther 41(7):1323–1345. https://doi.org/10.1016/j.clinthera.2019.04.021

    Article  PubMed  Google Scholar 

  11. Mankia K, Emery P (2016) Preclinical rheumatoid arthritis: progress toward prevention. Arthritis Rheum 68(4):779–788. https://doi.org/10.1002/art.39603

    Article  Google Scholar 

  12. Finckh A, Liang MH, van Herckenrode CM, de Pablo P (2006) Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: a meta-analysis. Arthritis Rheum 55(6):864–872. https://doi.org/10.1002/art.22353

    Article  PubMed  Google Scholar 

  13. Finckh A, Deane KD (2014) Prevention of rheumatic diseases: strategies, caveats, and future directions. Rheum Dis Clin N Am 40(4):771–785. https://doi.org/10.1016/j.rdc.2014.07.010

    Article  Google Scholar 

  14. Li CL, He J, Li ZG, Zheng LW, Hua H (2013) Effects of total glucosides of paeony for delaying onset of Sjogren's syndrome: an animal study. J Craniomaxillofac Surg 41(7):610–615. https://doi.org/10.1016/j.jcms.2012.11.042

    Article  PubMed  Google Scholar 

  15. Nagate T, Kawai J, Nakayama J (2009) Therapeutic and preventive effects of methotrexate on zymosan-induced arthritis in SKG mice. J Vet Med Sci 71(6):713–717

    Article  CAS  PubMed  Google Scholar 

  16. Frisell T, Holmqvist M, Kallberg H, Klareskog L, Alfredsson L, Askling J (2013) Familial risks and heritability of rheumatoid arthritis: role of rheumatoid factor/anti-citrullinated protein antibody status, number and type of affected relatives, sex, and age. Arthritis Rheum 65(11):2773–2782. https://doi.org/10.1002/art.38097

    Article  CAS  PubMed  Google Scholar 

  17. Mikuls T, LeVan T, Gould K, Yu F, Thiele G, Bynote K, Conn D, Jonas B (2012) Impact of interactions of cigarette smoking with NAT2 polymorphisms on rheumatoid arthritis risk in African Americans. Arthritis Rheum Vol. 64 (No. 3, March 2012,):655–664

  18. Sparks JA, Chang SC, Deane KD, Gan RW, Kristen Demoruelle M, Feser ML, Moss L, Buckner JH, Keating RM, Costenbader KH, Gregersen PK, Weisman MH, Mikuls TR, O'Dell JR, Michael Holers V, Norris JM, Karlson EW (2016) Associations of smoking and age with inflammatory joint signs among unaffected first-degree relatives of rheumatoid arthritis patients: results from studies of the etiology of rheumatoid arthritis. Arthritis Rheum 68(8):1828–1838. https://doi.org/10.1002/art.39630

    Article  CAS  Google Scholar 

  19. Alpizar-Rodriguez D (2018) Reproductive factors as predictors of disease development and disease progression in rheumatoid arthritis patients (thesis). University of Geneva, Geneva

    Google Scholar 

  20. Gerlag DM, Raza K, van Baarsen LG, Brouwer E, Buckley CD, Burmester GR, Gabay C, Catrina AI, Cope AP, Cornelis F, Dahlqvist SR, Emery P, Eyre S, Finckh A, Gay S, Hazes JM, van der Helm-van Mil A, Huizinga TW, Klareskog L, Kvien TK, Lewis C, Machold KP, Ronnelid J, van Schaardenburg D, Schett G, Smolen JS, Thomas S, Worthington J, Tak PP (2012) EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: report from the Study Group for Risk Factors for Rheumatoid Arthritis. Ann Rheum Dis 71(5):638–641. https://doi.org/10.1136/annrheumdis-2011-200990

    Article  PubMed  PubMed Central  Google Scholar 

  21. Alpizar-Rodriguez D, Brulhart L, Mueller RB, Moller B, Dudler J, Ciurea A, Walker UA, Von Muhlenen I, Kyburz D, Zufferey P, Mahler M, Bas S, Gascon D, Lamacchia C, Roux-Lombard P, Lauper K, Nissen MJ, Courvoisier DS, Gabay C, Finckh A (2017) The prevalence of anticitrullinated protein antibodies increases with age in healthy individuals at risk for rheumatoid arthritis. Clin Rheumatol 36(3):677–682. https://doi.org/10.1007/s10067-017-3547-3

    Article  CAS  PubMed  Google Scholar 

  22. Lahiri M, Luben RN, Morgan C, Bunn DK, Marshall T, Lunt M, Verstappen SM, Symmons DP, Khaw KT, Wareham N, Bruce IN (2014) Using lifestyle factors to identify individuals at higher risk of inflammatory polyarthritis (results from the European Prospective Investigation of Cancer-Norfolk and the Norfolk Arthritis Register--the EPIC-2-NOAR Study). Ann Rheum Dis 73(1):219–226. https://doi.org/10.1136/annrheumdis-2012-202481

    Article  PubMed  Google Scholar 

  23. van de Stadt LA, Witte BI, Bos WH, van Schaardenburg D (2013) A prediction rule for the development of arthritis in seropositive arthralgia patients. Ann Rheum Dis 72(12):1920–1926. https://doi.org/10.1136/annrheumdis-2012-202127

    Article  PubMed  Google Scholar 

  24. Alpizar-Rodriguez D, Finckh A (2017) Environmental factors and hormones in the development of rheumatoid arthritis. Semin Immunopathol 39(4):461–468. https://doi.org/10.1007/s00281-017-0624-2

    Article  CAS  PubMed  Google Scholar 

  25. van Dongen H, van Aken J, Lard LR, Visser K, Ronday HK, Hulsmans HM, Speyer I, Westedt ML, Peeters AJ, Allaart CF, Toes RE, Breedveld FC, Huizinga TW (2007) Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 56(5):1424–1432. https://doi.org/10.1002/art.22525

    Article  CAS  PubMed  Google Scholar 

  26. Machold KP, Landewe R, Smolen JS, Stamm TA, van der Heijde DM, Verpoort KN, Brickmann K, Vazquez-Mellado J, Karateev DE, Breedveld FC, Emery P, Huizinga TW (2010) The stop arthritis very early (SAVE) trial, an international multicentre, randomised, double-blind, placebo-controlled trial on glucocorticoids in very early arthritis. Ann Rheum Dis 69(3):495–502. https://doi.org/10.1136/ard.2009.122473

    Article  CAS  PubMed  Google Scholar 

  27. Emery P, Durez P, Dougados M, Legerton CW, Becker JC, Vratsanos G, Genant HK, Peterfy C, Mitra P, Overfield S, Qi K, Westhovens R (2010) Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial). Ann Rheum Dis 69(3):510–516. https://doi.org/10.1136/ard.2009.119016

    Article  CAS  PubMed  Google Scholar 

  28. Bos WH, Dijkmans BA, Boers M, van de Stadt RJ, van Schaardenburg D (2010) Effect of dexamethasone on autoantibody levels and arthritis development in patients with arthralgia: a randomised trial. Ann Rheum Dis 69(3):571–574. https://doi.org/10.1136/ard.2008.105767

    Article  CAS  PubMed  Google Scholar 

  29. Gerlag DM, Safy M, Maijer KI, Tang MW, Tas SW, Starmans-Kool MJF, van Tubergen A, Janssen M, de Hair M, Hansson M, de Vries N, Zwinderman AH, Tak PP (2019) Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study. Ann Rheum Dis 78(2):179–185. https://doi.org/10.1136/annrheumdis-2017-212763

    Article  CAS  PubMed  Google Scholar 

  30. Burgers LE, Allaart CF, Huizinga TWJ, van der Helm-van Mil AHM (2017) Brief report: clinical trials aiming to prevent rheumatoid arthritis cannot detect prevention without adequate risk stratification: a trial of methotrexate versus placebo in undifferentiated arthritis as an example. Arthritis Rheum 69(5):926–931. https://doi.org/10.1002/art.40062

    Article  CAS  Google Scholar 

  31. Klareskog L, Gregersen PK, Huizinga TW (2010) Prevention of autoimmune rheumatic disease: state of the art and future perspectives. Ann Rheum Dis 69(12):2062–2066. https://doi.org/10.1136/ard.2010.142109

    Article  CAS  PubMed  Google Scholar 

  32. Bykerk VP, Hazes JM (2010) When does rheumatoid arthritis start and can it be stopped before it does? Ann Rheum Dis 69(3):473–475. https://doi.org/10.1136/ard.2009.116020

    Article  PubMed  Google Scholar 

  33. Deane KD (2013) Can rheumatoid arthritis be prevented? Best Pract Res Clin Rheumatol 27(4):467–485. https://doi.org/10.1016/j.berh.2013.09.002

    Article  PubMed  PubMed Central  Google Scholar 

  34. Hilliquin S, Hugues B, Mitrovic S, Gossec L, Fautrel B (2018) Ability of disease-modifying antirheumatic drugs to prevent or delay rheumatoid arthritis onset: a systematic literature review and meta-analysis. Ann Rheum Dis 77(8):1099–1106. https://doi.org/10.1136/annrheumdis-2017-212612

    Article  CAS  PubMed  Google Scholar 

  35. Al-Laith M, Jasenecova M, Abraham S, Bosworth A, Bruce IN, Buckley CD, Ciurtin C, D'Agostino MA, Emery P, Gaston H, Isaacs JD, Filer A, Fisher BA, Huizinga TWJ, Ho P, Jacklin C, Lempp H, McInnes IB, Pratt AG, Ostor A, Raza K, Taylor PC, van Schaardenburg D, Shivapatham D, Wright AJ, Vasconcelos JC, Kelly J, Murphy C, Prevost AT, Cope AP (2019) Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol. Trials 20(1):429. https://doi.org/10.1186/s13063-019-3403-7

    Article  PubMed  PubMed Central  Google Scholar 

  36. Deane K, Holers M, Striebich C (2015) Strategy to prevent the onset of clinically-apparent rheumatoid arthritis (StopRA). US National Library of Medicine. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02603146. Accessed 30 October 2019

  37. Liu X, Tedeschi SK, Barbhaiya M, Leatherwood CL, Speyer CB, Lu B, Costenbader KH, Karlson EW, Sparks JA (2019) Impact and timing of smoking cessation on reducing risk of rheumatoid arthritis among women in the nurses’ health studies. Arthritis Care Res 71(7):914–924

  38. Sparks JA, Iversen MD, Miller Kroouze R, Mahmoud TG, Triedman NA, Kalia SS, Atkinson ML, Lu B, Deane KD, Costenbader KH, Green RC, Karlson EW (2014) Personalized risk estimator for rheumatoid arthritis (PRE-RA) family study: rationale and design for a randomized controlled trial evaluating rheumatoid arthritis risk education to first-degree relatives. Contemp Clin Trials 39(1):145–157. https://doi.org/10.1016/j.cct.2014.08.007

    Article  PubMed  PubMed Central  Google Scholar 

  39. Landewe RBM (2018) Overdiagnosis and overtreatment in rheumatology: a little caution is in order. Ann Rheum Dis 77(10):1394–1396. https://doi.org/10.1136/annrheumdis-2018-213700

    Article  PubMed  Google Scholar 

  40. Novotny F, Haeny S, Hudelson P, Escher M, Finckh A (2013) Primary prevention of rheumatoid arthritis: a qualitative study in a high-risk population. Joint Bone Spine 80(6):673–674. https://doi.org/10.1016/j.jbspin.2013.05.005

    Article  PubMed  Google Scholar 

  41. Falahee M, Finckh A, Raza K, Harrison M (2019) Preferences of patients and at-risk individuals for preventive approaches to rheumatoid arthritis. Clin Ther 41(7):1346–1354. https://doi.org/10.1016/j.clinthera.2019.04.015

    Article  PubMed  Google Scholar 

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Funding

Dr. Alpizar-Rodriguez was granted a Mexican National Council for Science and Technology (CONACYT) and a Swiss Government Excellence Scholarship for PhD studies.

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  1. Division of Rheumatology, Geneva University Hospital, Geneva, 26, Ave Beau-Séjour, 1211, Geneva, Switzerland

    Deshiré Alpizar-Rodriguez & Axel Finckh

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  1. Deshiré Alpizar-Rodriguez
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All authors contributed researching data for the article, discussion of its content, writing, reviewing, and editing of manuscript before submission.

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Correspondence to Deshiré Alpizar-Rodriguez.

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Alpizar-Rodriguez, D., Finckh, A. Is the prevention of rheumatoid arthritis possible?. Clin Rheumatol 39, 1383–1389 (2020). https://doi.org/10.1007/s10067-020-04927-6

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