Rheumatoid Arthritis: A Severe Disease That Preventive Approaches Would Greatly Benefit

  • John M. Davis III
    Address correspondence to: John M. Davis, III, MD, MS, Division of Rheumatology, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN. 55905, USA.
    Division of Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
    Search for articles by this author


      With the increased understanding of the etiology and pathogenesis of rheumatoid arthritis (RA) in recent decades, the notion of disease prevention has arisen. Contemplation of potential preventive strategies must be prefaced by a clear understanding of the rationale for the prevention, as opposed to the treatment, of a disease once established. RA is the most common systemic autoimmune rheumatic disease. The worldwide prevalence is 0.24%, and the lifetime cumulative prevalence approaches 4% in women and 2% in men. RA has severe manifestations leading to chronic pain, impaired quality of life, inability to participate in social and work activities, disability, extra-articular manifestations, and premature mortality. Unfortunately, patients often experience a long duration of symptoms prior to diagnosis, owing to inadequate awareness in the general population, limitations of diagnostic assessments in the early phases of the disease, and a lack of access to rheumatologists globally. Despite the development of novel targeted therapies and substantial improvements in treatment strategies, up to 60% of patients fail to respond adequately to any particular treatment strategy, and 30% of those fail to respond to multiple agents. Therefore, there remains a large proportion of patients who fail to achieve clinical remission and patient-acceptable symptom states. Treatments for RA may be associated with a variety of complications, limiting their sustained usefulness, particularly as related to an increased risk for serious infections. Advancements in therapies have curtailed the previous main driver of mortality, cardiovascular disease, but overall mortality remains elevated in many studies of persons with RA compared to the general population. This commentary reviews the rationale in detail and introduces a clear implication that the ideal strategy would be to develop a means of preventing the onset of clinically apparent joint inflammation among individuals at risk.


      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


        • Aletaha D.
        • Smolen J.S.
        Diagnosis and management of rheumatoid arthritis: a review.
        JAMA. 2018; 320: 1360-1372
        • Raza K.
        • Holers V.M.
        • Gerlag D.
        Nomenclature of the stages of rheumatoid arthritis development.
        Clin Ther. 2019; 41: 1279-1285
        • Demoruelle M.K.
        Mucosal biology and the development of rheumatoid arthritis: potential for prevention by targeting mucosal processes.
        Clin Ther. 2019; 41: 1270-1278
        • Deane K.D.
        • Holers V.M.
        Natural history of rheumatoid arthritis.
        Clin Ther. 2019; 41: 1256-1269
        • Cross M.
        • Smith E.
        • Hoy D.
        • et al.
        The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study.
        Ann Rheum Dis. 2014; 73: 1316-1322
        • Crowson C.S.
        • Matteson E.L.
        • Myasoedova E.
        • et al.
        The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases.
        Arthritis Rheum. 2011; 63: 633-639
        • Martikainen J.A.
        • Kautiainen H.
        • Rantalaiho V.
        • Puolakka K.T.
        Longterm work productivity costs due to absenteeism and permanent work disability in patients with early rheumatoid arthritis: a nationwide register study of 7831 patients.
        J Rheumatol. 2016; 43: 2101-2105
        • van Vilsteren M.
        • Boot C.R.
        • Knol D.L.
        • et al.
        Productivity at work and quality of life in patients with rheumatoid arthritis.
        BMC Musculoskelet Disord. 2015; 16: 107
        • van der Zee-Neuen A.
        • Putrik P.
        • Ramiro S.
        • et al.
        Large country differences in work outcomes in patients with RA—an analysis in the multinational study COMORA.
        Arthritis Res Ther. 2017; 19: 216
        • Svensson B.
        • Andersson M.
        • Forslind K.
        • Ajeganova S.
        • Hafstrom I.
        Persistently active disease is common in patients with rheumatoid arthritis, particularly in women: a long-term inception cohort study.
        Scand J Rheumatol. 2016; 45: 448-455
        • Ishida M.
        • Kuroiwa Y.
        • Yoshida E.
        • et al.
        Residual symptoms and disease burden among patients with rheumatoid arthritis in remission or low disease activity: a systematic literature review.
        Mod Rheumatol. 2018; 28: 789-799
        • Taylor P.C.
        • Moore A.
        • Vasilescu R.
        • Alvir J.
        • Tarallo M.
        A structured literature review of the burden of illness and unmet needs in patients with rheumatoid arthritis: a current perspective.
        Rheumatol Int. 2016; 36: 685-695
        • Altawil R.
        • Saevarsdottir S.
        • Wedren S.
        • Alfredsson L.
        • Klareskog L.
        • Lampa J.
        Remaining pain in early rheumatoid arthritis patients treated with methotrexate.
        Arthritis Care Res (hoboken). 2016; 68: 1061-1068
        • Bilberg A.
        • Bremell T.
        • Bjersing J.
        • Mannerkorpi K.
        High prevalence of widespread pain in women with early rheumatoid arthritis.
        Scand J Rheumatol. 2018; 47: 447-454
        • Zhang A.
        • Lee Y.C.
        Mechanisms for joint pain in rheumatoid arthritis (RA): from cytokines to central sensitization.
        Curr Osteoporos Rep. 2018; 16: 603-610
        • Lee Y.C.
        • Fine A.
        • Protsenko E.
        • et al.
        Brain correlates of continuous pain in rheumatoid arthritis as measured by pulsed arterial spin labeling.
        Arthritis Care Res (hoboken). 2019; 71: 308-318
        • Giles J.T.
        Extra-articular manifestations and comorbidity in rheumatoid arthritis: potential impact of pre-clinical rheumatoid arthritis prevention.
        Clin Ther. 2019; 41: 1246-1255
        • Holmqvist M.
        • Ljung L.
        • Askling J.
        Acute coronary syndrome in new-onset rheumatoid arthritis: a population-based nationwide cohort study of time trends in risks and excess risks.
        Ann Rheum Dis. 2017; 76: 1642-1647
        • Ni Mhuircheartaigh O.M.
        • Matteson E.L.
        • Green A.B.
        • Crowson C.S.
        Trends in serious infections in rheumatoid arthritis.
        J Rheumatol. 2013; 40: 611-616
        • Widdifield J.
        • Bernatsky S.
        • Paterson J.M.
        • et al.
        Serious infections in a population-based cohort of 86,039 seniors with rheumatoid arthritis.
        Arthritis Care Res (hoboken). 2013; 65: 353-361
        • Michet 3rd, C.J.
        • Strobova K.
        • Achenbach S.
        • Crowson C.S.
        • Matteson E.L.
        Hospitalization rates and utilization among patients with rheumatoid arthritis: a population-based study from 1987 to 2012 in Olmsted County, Minnesota.
        Mayo Clin Proc. 2015; 90: 176-183
        • Holmqvist M.
        • Ljung L.
        • Askling J.
        Mortality following new-onset rheumatoid arthritis: has modern rheumatology had an impact?.
        Ann Rheum Dis. 2018; 77: 85-91
        • 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. 2017; 76: 1057-1063
        • 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
        • Stack R.J.
        • Llewellyn Z.
        • Deighton C.
        • Kiely P.
        • Mallen C.D.
        • Raza K.
        General practitioners' perspectives on campaigns to promote rapid help-seeking behaviour at the onset of rheumatoid arthritis.
        Scand J Prim Health Care. 2014; 32: 37-43
        • Battafarano D.F.
        • Ditmyer M.
        • Bolster M.B.
        • et al.
        2015 American College of Rheumatology workforce study: supply and demand projections of adult rheumatology workforce, 2015-2030.
        Arthritis Care Res (hoboken). 2018; 70: 617-626
        • Barber C.E.
        • Jewett L.
        • Badley E.M.
        • et al.
        Stand up and be counted: measuring and mapping the rheumatology workforce in Canada.
        J Rheumatol. 2017; 44: 248-257
        • Puchner R.
        • Hochreiter R.
        • Pieringer H.
        • Vavrovsky A.
        Improving patient flow of people with rheumatoid arthritis has the potential to simultaneously improve health outcomes and reduce direct costs.
        BMC Musculoskelet Disord. 2017; 18: 7
        • Doherty E.
        • O'Neill C.
        Estimating the health-care usage associated with osteoarthritis and rheumatoid arthritis in an older adult population in Ireland.
        J Pub Health (oxf). 2014; 36: 504-510
        • Xu C.
        • Wang X.
        • Mu R.
        • et al.
        Societal costs of rheumatoid arthritis in China: a hospital-based cross-sectional study.
        Arthritis Care Res (hoboken). 2014; 66: 523-531
        • Shi Q.
        • Li K.J.
        • Treuer T.
        • et al.
        Estimating the response and economic burden of rheumatoid arthritis patients treated with biologic disease-modifying antirheumatic drugs in Taiwan using the National Health Insurance Research Database (NHIRD).
        PLoS One. 2018; 13e0193489
        • Shafrin J.
        • Tebeka M.G.
        • Price K.
        • Patel C.
        • Michaud K.
        The economic burden of ACPA-positive status among patients with rheumatoid arthritis.
        J Manag Care Spec Pharm. 2018; 24: 4-11
        • Strand V.
        • Tundia N.
        • Song Y.
        • Macaulay D.
        • Fuldeore M.
        Economic burden of patients with inadequate response to targeted immunomodulators for rheumatoid arthritis.
        J Manag Care Spec Pharm. 2018; 24: 344-352
        • Shahabi A.
        • Shafrin J.
        • Zhao L.
        • et al.
        The economic burden of switching targeted disease-modifying anti-rheumatic drugs among rheumatoid arthritis patients.
        J Med Econ. 2019; : 1-9
        • Betts K.A.
        • Griffith J.
        • Ganguli A.
        • Li N.
        • Douglas K.
        • Wu E.Q.
        Economic burden and treatment patterns of cycling between conventional synthetic disease-modifying antirheumatic drugs among biologic-treated patients with rheumatoid arthritis.
        Clin Ther. 2016; 38: 1205-1216
        • van der Elst K.
        • Meyfroidt S.
        • De Cock D.
        • et al.
        Unraveling patient-preferred health and treatment outcomes in early rheumatoid arthritis: a longitudinal qualitative study.
        Arthritis Care Res (hoboken). 2016; 68: 1278-1287
        • Yazdany J.
        • Dudley R.A.
        • Chen R.
        • Lin G.A.
        • Tseng C.W.
        Coverage for high-cost specialty drugs for rheumatoid arthritis in Medicare Part D.
        Arthritis Rheumatol. 2015; 67: 1474-1480
        • McCulley C.
        • Katz P.
        • Trupin L.
        • Yelin E.H.
        • Barton J.L.
        Association of medication beliefs, self-efficacy, and adherence in a diverse cohort of adults with rheumatoid arthritis.
        J Rheumatol. 2018; 45: 1636-1642
        • Shaw Y.
        • Metes I.D.
        • Michaud K.
        • et al.
        Rheumatoid arthritis patients' motivations for accepting or resisting disease-modifying antirheumatic drug treatment regimens.
        Arthritis Care Res (hoboken). 2018; 70: 533-541
        • van Nies J.A.
        • Krabben A.
        • Schoones J.W.
        • Huizinga T.W.
        • Kloppenburg M.
        • van der Helm-van Mil A.H.
        What is the evidence for the presence of a therapeutic window of opportunity in rheumatoid arthritis? A systematic literature review.
        Ann Rheum Dis. 2014; 73: 861-870
        • van Nies J.A.
        • Tsonaka R.
        • Gaujoux-Viala C.
        • Fautrel B.
        • van der Helm-van Mil A.H.
        Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: does a window of opportunity exist? Results on the Leiden early arthritis clinic and ESPOIR cohorts.
        Ann Rheum Dis. 2015; 74: 806-812
        • Singh J.A.
        • Saag K.G.
        • Bridges Jr., S.L.
        • et al.
        2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis.
        Arthritis Rheumatol. 2016; 68: 1-26
        • Stolshek B.S.
        • Wade S.
        • Mutebi A.
        • De A.P.
        • Wade R.L.
        • Yeaw J.
        Two-year adherence and costs for biologic therapy for rheumatoid arthritis.
        Am J Manag Care. 2018; 24: Sp315-Sp321
        • Kuusalo L.
        • Puolakka K.
        • Kautiainen H.
        • et al.
        High burden of adverse events is associated with reduced remission rates in early rheumatoid arthritis.
        Clin Rheumatol. 2018; 37: 1689-1694
        • Raheel S.
        • Matteson E.L.
        • Crowson C.S.
        • Myasoedova E.
        Improved flare and remission pattern in rheumatoid arthritis over recent decades: a population-based study.
        Rheumatology (Oxford). 2017; 56: 2154-2161
        • Wailoo A.
        • Hock E.S.
        • Stevenson M.
        • et al.
        The clinical effectiveness and cost-effectiveness of treat-to-target strategies in rheumatoid arthritis: a systematic review and cost-effectiveness analysis.
        Health Technol Assess. 2017; 21: 1-258
        • Chester Wasko M.
        • Dasgupta A.
        • Ilse Sears G.
        • Fries J.F.
        • Ward M.M.
        Prednisone use and risk of mortality in patients with rheumatoid arthritis: moderation by use of disease-modifying antirheumatic drugs.
        Arthritis Care Res (hoboken). 2016; 68: 706-710
        • Isaacs J.
        • Iqbal K.
        Potential pharmacological targets for the prevention of rheumatoid arthritis.
        Clin Ther. 2019; 41: 1312-1322
        • van Boheemen L.
        • van Schaardenburg D.
        Predicting rheumatoid arthritis in at-risk individuals.
        Clin Ther. 2019; 41: 1250-1298
        • Zaccardelli A.
        • Ford J.
        • Sparks J.A.
        Potential of lifestyle changes for reducing the risk of developing rheumatoid arthritis: is an ounce of prevention worth a pound of cure?.
        Clin Ther. 2019; 41: 1323-1345
        • Cope A.P.
        Considerations for optimal trial design for rheumatoid arthritis prevention studies.
        Clin Ther. 2019; 41: 1299-1311