Top

Published in:

01-05-2020 | Joint Pain | Perspectives in Rheumatology

Is the prevention of rheumatoid arthritis possible?

Authors: Deshiré Alpizar-Rodriguez, Axel Finckh

Published in: Clinical Rheumatology | Issue 5/2020

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.

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 PubMedCrossRef

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 PubMedCrossRef

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):1620–1622PubMed

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 CrossRef

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):264–266PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 CrossRef

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 PubMedCrossRef

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 CrossRef

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 PubMedCrossRef

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):713–717PubMedCrossRef

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 PubMedCrossRef

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 CrossRef

19.

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

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 CrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

Title: Is the prevention of rheumatoid arthritis possible?
Authors: Deshiré Alpizar-Rodriguez
Axel Finckh
Publication date: 01-05-2020
Publisher: Springer London
Keywords: Joint Pain
Abatacept
Arthritis
Rheumatoid Arthritis
Published in: Clinical Rheumatology / Issue 5/2020
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI: https://doi.org/10.1007/s10067-020-04927-6

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2020

Relapses in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a retrospective study

Elevated serum interleukin-34 level in juvenile systemic lupus erythematosus and disease activity

At the crossroads of gout and psoriatic arthritis: “psout”

Evaluation of urate-lowering therapy in hyperuricemia patients: a systematic review and Bayesian network meta-analysis of randomized controlled trials

The clinical value of interleukins-8, -10, and -17 in idiopathic granulomatous mastitis

Mortality of Chinese patients with polymyositis and dermatomyositis

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage