Preferences of Patients and At-risk Individuals for Preventive Approaches to Rheumatoid Arthritis

  • Marie Falahee
    Corresponding author.
    Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
    Search for articles by this author
  • Axel Finckh
    Department of Rheumatology, Geneva University Hospital, Geneva, Switzerland
    Search for articles by this author
  • Karim Raza
    Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

    Department of Rheumatology, Sandwell & West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom

    Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence, MRC Arthritis Research UK Centre for Musculoskeletal Ageing Research, NIHR Biomedical Research Centre, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
    Search for articles by this author
  • Mark Harrison
    Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada

    Centre for Health Evaluation and Outcome Sciences, St. Paul's Hospital, Vancouver, British Columbia, Canada

    Arthritis Research Centre of Canada, Richmond, British Columbia, Canada
    Search for articles by this author


      Effective treatments for rheumatoid arthritis (RA) are available and can lead to remission for some patients, but most patients remain on potentially toxic and expensive medications in the long term. Interest is increasingly turning to the disease phases preceding the development of RA that represent opportunities for preventive interventions. At-risk target populations include individuals with genetic and environmental risk factors, those who have developed systemic autoimmunity, and those who have developed clinically suspect symptoms (eg, arthralgias without synovitis, or an early arthritis). Ongoing prospective studies will inform the development of increasingly accurate predictive tools to identify individuals at risk of developing RA. Furthermore, a range of preventive approaches has been suggested, including lifestyle modification (eg, smoking cessation) and pharmacologic interventions (eg, hydroxychloroquine, methotrexate, abatacept, rituximab) that are currently the subject of randomized controlled trials. As prediction and prevention of RA evolve, it is increasingly likely that individuals at risk (including asymptomatic individuals) may be faced with complex decisions about whether to accept assessment of their risk status or to take a preventive intervention associated with risk of serious adverse events and uncertain benefit. Acceptance of preventive medication in other contexts can be low. For example, <25% of women at high risk of breast cancer are willing to take preventive hormonal treatments. Actual uptake is lower still. Patients’ beliefs and preferences predict treatment uptake and adherence. Before the dream of preventing RA can become reality, health care providers need to understand the perspectives of individuals in the target population and to identify barriers and facilitators for this approach. This commentary reviews what is currently known about the perspectives of patients and individuals at risk about predictive and preventive approaches for RA and identifies gaps to be addressed to inform the development of efficient preventive strategies.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Therapeutics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • van der Linden M.P.
        • le Cessie S.
        • Raza K.
        • et al.
        Long-term impact of delay in assessment of patients with early arthritis.
        Arthritis Rheum. 2010; 62: 3537-3546
        • Smolen J.S.
        • Landewe R.
        • Bijlsma J.
        • et al.
        EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update.
        Ann Rheum Dis. 2017; 76: 960-977
        • National Rheumatoid Arthritis Society
        Economic Burden of RA Report.
        • Birnbaum H.
        • Pike C.
        • Kaufman R.
        • Marynchenko M.
        • Kidolezi Y.
        • Cifaldi M.
        Societal cost of rheumatoid arthritis patients in the US.
        Curr Med Res Opin. 2010; 26: 77-90
        • Raza K.
        • Gerlag D.M.
        Preclinical inflammatory rheumatic diseases: an overview and relevant nomenclature.
        Rheum Dis Clin North Am. 2014; 40: 569-580
        • van Steenbergen H.W.
        • Aletaha D.
        • Beaart-van de Voorde L.J.
        • et al.
        EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis.
        Ann Rheum Dis. 2017; 76: 491-496
        • Gerlag D.M.
        • Raza K.
        • van Baarsen L.G.
        • et al.
        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. 2012; 71: 638-641
        • van de Stadt L.A.
        • Witte B.I.
        • Bos W.H.
        • van Schaardenburg D.
        A prediction rule for the development of arthritis in seropositive arthralgia patients.
        Ann Rheum Dis. 2013; 72: 1920-1926
        • van der Helm-van Mil A.H.
        • Detert J.
        • le Cessie S.
        • et al.
        Validation of a prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis: moving toward individualized treatment decision-making.
        Arthritis Rheum. 2008; 58: 2241-2247
        • Lubbers J.
        • Brink M.
        • van de Stadt L.A.
        • et al.
        The type I IFN signature as a biomarker of preclinical rheumatoid arthritis.
        Ann Rheum Dis. 2013; 72: 776-780
        • Lubbers J.
        • Vosslamber S.
        • van de Stadt L.A.
        • et al.
        B cell signature contributes to the prediction of RA development in patients with arthralgia.
        Ann Rheum Dis. 2015; 74: 1786-1788
        • Tak P.P.
        • Doorenspleet M.E.
        • de Hair M.J.H.
        • et al.
        Dominant B cell receptor clones in peripheral blood predict onset of arthritis in individuals at risk for rheumatoid arthritis.
        Ann Rheum Dis. 2017; 76: 1924-1930
        • van der Ven M.
        • van der Veer-Meerkerk M.
        • Ten Cate D.F.
        • et al.
        Absence of ultrasound inflammation in patients presenting with arthralgia rules out the development of arthritis.
        Arthritis Res Ther. 2017; 19: 202
        • Filer A.
        • de Pablo P.
        • Allen G.
        • et al.
        Utility of ultrasound joint counts in the prediction of rheumatoid arthritis in patients with very early synovitis.
        Ann Rheum Dis. 2011; 70: 500-507
        • Sahbudin I.
        • Pickup L.
        • Nightingale P.
        • et al.
        The role of ultrasound-defined tenosynovitis and synovitis in the prediction of rheumatoid arthritis development.
        Rheumatology (Oxford). 2018; 57: 1243-1252
        • Kolfenbach J.
        • Deane K.
        • Derber L.
        • et al.
        A prospective approach to investigating the natural history of preclinical rheumatoid arthritis (RA) using first-degree relatives of probands with RA.
        Arthritis Rheum. 2009; 61: 1735-1742
        • Cope A.P.
        Emerging therapies for pre-RA.
        Best Pract Res Clin Rheumatol. 2017; 31: 99-111
        • Kallberg H.
        • Ding B.
        • Padyukov L.
        • et al.
        Smoking is a major preventable risk factor for rheumatoid arthritis: estimations of risks after various exposures to cigarette smoke.
        Ann Rheum Dis. 2011; 70: 508-511
        • Karlson E.W.
        • van Schaardenburg D.
        • van der Helm-van Mil A.H.
        Strategies to predict rheumatoid arthritis development in at-risk populations.
        Rheumatology (Oxford). 2016; 55: 6-15
        • Bos W.H.
        • Dijkmans B.A.
        • Boers M.
        • van de Stadt R.J.
        • van Schaardenburg D.
        Effect of dexamethasone on autoantibody levels and arthritis development in patients with arthralgia: a randomised trial.
        Ann Rheum Dis. 2010; 69: 571-574
        • Verstappen S.M.M.
        • McCoy M.J.
        • Roberts C.
        • Dale N.E.
        • Hassell A.B.
        • Symmons D.P.M.
        Beneficial effects of a 3-week course of intramuscular glucocorticoid injections in patients with very early inflammatory polyarthritis: results of the STIVEA trial.
        Ann Rheum Dis. 2010; 69: 503-509
        • Gerlag D.M.
        • Safy M.
        • Maijer K.I.
        • et al.
        Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study.
        Ann Rheum Dis. 2019; 78: 179-185
        • Gigerenzer G.
        • Gaissmaier W.
        • Kurz-Milcke E.
        • Schwartz L.M.
        • Woloshin S.
        Helping doctors and patients make sense of health statistics.
        Psychol Sci Public Interest. 2007; 8: 53-96
        • Smerecnik C.M.
        • Mesters I.
        • Verweij E.
        • de Vries N.K.
        • de Vries H.
        A systematic review of the impact of genetic counseling on risk perception accuracy.
        J Genet Couns. 2009; 18: 217-228
        • Carling C.L.
        • Kristoffersen D.T.
        • Montori V.M.
        • et al.
        The effect of alternative summary statistics for communicating risk reduction on decisions about taking statins: a randomized trial.
        Plos Med. 2009; 6e1000134
        • Peters E.
        • Hart P.S.
        • Fraenkel L.
        Informing patients: the influence of numeracy, framing, and format of side effect information on risk perceptions.
        Med Decis Making. 2011; 31: 432-436
        • Waters E.A.
        • Weinstein N.D.
        • Colditz G.A.
        • Emmons K.
        Explanations for side effect aversion in preventive medical treatment decisions.
        Health Psychol. 2009; 28: 201-209
        • Ropka M.E.
        • Keim J.
        • Philbrick J.T.
        Patient decisions about breast cancer chemoprevention: a systematic review and meta-analysis.
        J Clin Oncol. 2010; 28: 3090-3095
        • Marshall I.J.
        • Wolfe C.D.
        • McKevitt C.
        Lay perspectives on hypertension and drug adherence: systematic review of qualitative research.
        BMJ. 2012; 345e3953
        • Scoville E.A.
        • Ponce de Leon Lovaton P.
        • Shah N.D.
        • Pencille L.J.
        • Montori V.M.
        Why do women reject bisphosphonates for osteoporosis? A videographic study.
        PLoS One. 2011; 6: e18468
        • Fried T.R.
        • Tinetti M.E.
        • Towle V.
        • O'Leary J.R.
        • Iannone L.
        Effects of benefits and harms on older persons' willingness to take medication for primary cardiovascular prevention.
        Arch Intern Med. 2011; 171: 923-928
        • Llewellyn-Thomas H.A.
        • Paterson J.M.
        • Carter J.A.
        • et al.
        Primary prevention drug therapy: can it meet patients' requirements for reduced risk?.
        Med Decis Making. 2002; 22: 326-339
        • Fraenkel L.
        • Gulanski B.
        • Wittink D.
        Patient willingness to take teriparatide.
        Patient Educ Couns. 2007; 65: 237-244
        • Thorneloe R.J.
        • Horne R.
        • Side L.
        • et al.
        Beliefs about medication and uptake of preventive therapy in women at increased risk of breast cancer: results from a multicenter prospective study.
        Clin Breast Cancer. 2019; 19: e116-e126
        • Neuner J.M.
        • Schapira M.M.
        Patient perceptions of osteoporosis treatment thresholds.
        J Rheumatol. 2014; 41: 516-522
        • Burgers L.E.
        • Allaart C.F.
        • Huizinga T.W.J.
        • van der Helm-van Mil A.H.M.
        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 Rheumatol. 2017; 69: 926-931
        • Sparks J.A.
        • Chen C.Y.
        • Jiang X.
        • et al.
        Improved performance of epidemiologic and genetic risk models for rheumatoid arthritis serologic phenotypes using family history.
        Ann Rheum Dis. 2015; 74: 1522-1529
        • Boeters D.M.
        • Raza K.
        • Vander Helm-van Mil A.H.M.
        Which patients presenting with arthralgia eventually develop rheumatoid arthritis? The current state of the art.
        RMD Open. 2017; 3e000479
        • Prado M.G.
        • Iversen M.D.
        • Yu Z.
        • et al.
        Effectiveness of a web-based personalized rheumatoid arthritis risk tool with or without a health educator for knowledge of rheumatoid arthritis risk factors.
        Arthritis Care Res (Hoboken). 2018; 70: 1421-1430
        • Sparks J.A.
        • Iversen M.D.
        • Yu Z.
        • et al.
        Disclosure of personalized rheumatoid arthritis risk using genetics, biomarkers, and lifestyle factors to motivate health behavior improvements: a randomized controlled trial.
        Arthritis Care Res. 2018; 70: 823-833
        • Hollands G.J.
        • French D.P.
        • Griffin S.J.
        • et al.
        The impact of communicating genetic risks of disease on risk-reducing health behaviour: systematic review with meta-analysis.
        BMJ. 2016; 352: i1102
        • Li S.X.
        • Ye Z.
        • Whelan K.
        • Truby H.
        The effect of communicating the genetic risk of cardiometabolic disorders on motivation and actual engagement in preventative lifestyle modification and clinical outcome: a systematic review and meta-analysis of randomised controlled trials.
        Br J Nutr. 2016; 116: 924-934
        • Lautenbach D.M.
        • Christensen K.D.
        • Sparks J.A.
        • Green R.C.
        Communicating genetic risk information for common disorders in the era of genomic medicine.
        Annu Rev Genomics Hum Genet. 2013; 14: 491-513
        • Bayliss K.
        • Raza K.
        • Simons G.
        • et al.
        Perceptions of predictive testing for those at risk of developing a chronic inflammatory disease: a meta-synthesis of qualitative studies.
        J Risk Res. 2018; 21: 167-189
        • Falahee M.
        • Simons G.
        • Raza K.
        • Stack R.J.
        Healthcare professionals’ perceptions of risk in the context of genetic testing for the prediction of chronic disease: a qualitative metasynthesis.
        J Risk Res. 2018; 21: 129-166
        • Stack R.J.
        • van Tuyl L.H.
        • Sloots M.
        • et al.
        Symptom complexes in patients with seropositive arthralgia and in patients newly diagnosed with rheumatoid arthritis: a qualitative exploration of symptom development.
        Rheumatology (Oxford). 2014; 53: 1646-1653
      1. van Tuyl LH, Stack RJ, Sloots M, et al. Impact of symptoms on daily life in people at risk of rheumatoid arthritis. Musculoskeltal Care.14:169–173.

        • Newsum E.C.
        • van der Helm-van Mil A.H.
        • Kaptein A.A.
        Views on clinically suspect arthralgia: a focus group study.
        Clin Rheumatol. 2016; 35: 1347-1352
        • Marshall A.A.
        • Zaccardelli A.
        • Yu Z.
        • et al.
        Effect of communicating personalized rheumatoid arthritis risk on concern for developing RA: a randomized controlled trial.
        Patient Educ Couns. 2018; 102: 976-983
        • Stack R.J.
        • Stoffer M.
        • Englbrecht M.
        • et al.
        Perceptions of risk and predictive testing held by the first-degree relatives of patients with rheumatoid arthritis in England, Austria and Germany: a qualitative study.
        BMJ Open. 2016; 6e010555
        • Falahee M.
        • Simons G.
        • Buckley C.D.
        • Hansson M.
        • Stack R.J.
        • Raza K.
        Patients' perceptions of their relatives' risk of developing rheumatoid arthritis and of the potential for risk communication, prediction, and modulation.
        Arthritis Care Res (Hoboken). 2017; 69: 1558-1565
        • Mosor E.
        • Stoffer-Marx M.
        • Steiner G.
        • et al.
        I would never take preventive medication! Perspectives and information needs of people who underwent predictive tests for rheumatoid arthritis.
        Arthritis Care Res. 2019;
        • Collins J.
        • Ryan L.
        • Truby H.
        A systematic review of the factors associated with interest in predictive genetic testing for obesity, type II diabetes and heart disease.
        J Hum Nutr Diet. 2014; 27: 479-488
        • Konda V.
        • Huo D.
        • Hermes G.
        • Liu M.
        • Patel R.
        • Rubin D.T.
        Do patients with inflammatory bowel disease want genetic testing?.
        Inflamm Bowel Dis. 2006; 12: 497-502
        • Bansback N.
        • Harrison M.
        • Marra C.
        Does introducing imprecision around probabilities for benefit and harm influence the way people value treatments?.
        Med Decis Making. 2016; 36: 490-502
        • Hunter D.J.
        Uncertainty in the era of precision medicine.
        N Engl J Med. 2016; 375: 711-713
        • Novotny F.
        • Haeny S.
        • Hudelson P.
        • Escher M.
        • Finckh A.
        Primary prevention of rheumatoid arthritis: a qualitative study in a high-risk population.
        Jt Bone Spine. 2013; 80: 673-674
        • Munro S.
        • Spooner L.
        • Milbers K.
        • Hudson M.
        • Koehn C.
        • Harrison M.
        Perspectives of patients, first-degree relatives and rheumatologists on preventive treatments for rheumatoid arthritis: a qualitative analysis.
        BMC Rheumatol. 2018; 2: 18
        • Simons G.
        • Stack R.J.
        • Stoffer-Marx M.
        • et al.
        Perceptions of first-degree relatives of patients with rheumatoid arthritis about lifestyle modifications and pharmacological interventions to reduce the risk of rheumatoid arthritis development: a qualitative interview study.
        BMC Rheumatol. 2018; 2: 31
        • Barnabe C.
        • Jones C.A.
        • Bernatsky S.
        • et al.
        Inflammatory arthritis prevalence and health services use in the First Nations and non–First Nations populations of Alberta, Canada.
        Arthritis Care Res (Hoboken). 2017; 69: 467-474
        • Oen K.
        • Robinson D.B.
        • Nickerson P.
        • et al.
        Familial seropositive rheumatoid arthritis in North American Native families: effects of shared epitope and cytokine genotypes.
        J Rheumatol. 2005; 32: 983
        • Finckh A.
        • Escher M.
        • Liang M.H.
        • Bansback N.
        Preventive treatments for rheumatoid arthritis: issues regarding patient preferences.
        Curr Rheumatol Rep. 2016; 18: 51
        • Harrison M.S.L.
        • Hudson M.
        • Koehn C.
        • Finckh A.
        Bansback N Preventing rheumatoid arthritis: north American perspectives on the risk of developing the disease and of potential preventative interventions.
        Arthritis Rheumatol. 2017; 69
        • Harrison M.B.N.
        • Spooner L.
        • Koehn C.
        • Hudson M.
        Preventing rheumatoid arthritis (pre-RA): preferences of potential recipients, patients and health care professionals for preventive treatment.
        J Rheumatol. 2018; 45
        • De Wit G.A.
        • Busschbach J.J.
        • De Charro F.T.
        Sensitivity and perspective in the valuation of health status: whose values count?.
        Health Econ. 2000; 9: 109-126
        • Hope H.F.
        • Bluett J.
        • Barton A.
        • Hyrich K.L.
        • Cordingley L.
        • Verstappen S.M.
        Psychological factors predict adherence to methotrexate in rheumatoid arthritis; findings from a systematic review of rates, predictors and associations with patient-reported and clinical outcomes.
        RMD Open. 2016; 2e000171
        • Smolen J.S.
        • Gladman D.
        • McNeil H.P.
        • et al.
        Predicting adherence to therapy in rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis: a large cross-sectional study.
        RMD Open. 2019; 5e000585
        • Quaife M.
        • Terris-Prestholt F.
        • Di Tanna G.L.
        • Vickerman P.
        How well do discrete choice experiments predict health choices? A systematic review and meta-analysis of external validity.
        Eur J Health Econ. 2018; 19: 1053-1066
        • Mohammadi T.
        • Bansback N.
        • Marra F.
        • et al.
        Testing the external validity of a discrete choice experiment method: an application to latent tuberculosis infection treatment.
        Value Health. 2017; 20: 969-975