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  • Review Article
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The influence of ageing on the development and management of rheumatoid arthritis

Nature Reviews Rheumatology volume 9, pages 604–613 (2013)Cite this article

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Abstract

The population of elderly individuals with rheumatoid arthritis (RA) is expanding, due mainly to increasing life expectancy. A variety of theories have been proposed to explain the ageing process, including accumulation of DNA damage and resultant changes in biological processes. Such changes can influence the development and/or course of disease. Furthermore, alterations in biological function determine the biological age—as opposed to chronological age—of an individual, which strongly influences their ability to cope with disease. Moreover, comorbidities are more frequent in elderly individuals. Together, these factors complicate treatment of disease and necessitate careful patient management. Indeed, although evidence from clinical trials suggests that DMARDs and biologic agents have good efficacy and are well tolerated in elderly patients with RA, such individuals are often undertreated and inadequately managed. Unfortunately, insufficient data are available for the development of evidence-based guidelines for this population, as elderly patients are often excluded from clinical trials owing to age restrictions or comorbidities. Thus, additional clinical studies in elderly patients are warranted, with treatment regimens tailored according to vitality or frailty parameters. This Review focuses on the pathophysiological aspects of ageing and their implications for the management of RA in elderly patients.

Key Points

  • As a consequence of increasing life expectancies worldwide, the number of elderly people with rheumatoid arthritis (RA) is growing

  • Evidence-based guidelines for management of RA in elderly individuals are lacking owing to insufficient clinical data

  • Data suggest that elderly individuals with RA are undertreated and inadequately managed, despite DMARDs and biologic therapies being effective and seemingly well tolerated in this population

  • Therapeutic decision making in elderly patients with RA needs to incorporate consideration of patient frailty and comorbidities

  • The level of disease activity set as the therapeutic goal might differ according to the patient's biological age or presence of particular risk factors for infection

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Figure 1: Major changes of the immune system with ageing.
Figure 2: Post-thymic differentiation of naive T cells after antigen presentation by professional APCs.
Figure 3: Challenges facing the management of RA in elderly adults.

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References

  1. Konrat, C. et al. Underrepresentation of elderly people in randomised controlled trials. The example of trials of 4 widely prescribed drugs. PLoS ONE 7, e33559 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Macieira-Coelho, A. Cell division and aging of the organism. Biogerontology 12, 503–515 (2011).

    Article  PubMed  Google Scholar 

  3. Sperka, T., Wang, J. & Rudolph, K. L. DNA damage checkpoints in stem cells, ageing and cancer. Nat. Rev. Mol. Cell. Biol. 13, 579–590 (2012).

    Article  CAS  PubMed  Google Scholar 

  4. Kirkwood, T. B. Evolution of ageing. Nature 270 301–304 (1977).

    Article  CAS  PubMed  Google Scholar 

  5. Kirkwood, T. L., Kapahi, P. & Shanley, D. P. Evolution, stress, and longevity. J. Anat. 197, 587–590 (2000).

    Article  PubMed Central  PubMed  Google Scholar 

  6. Ljubuncic, P. & Reznick, A. Z. The evolutionary theories of aging revisited—a mini-review. Gerontology 55, 205–216 (2009).

    Article  CAS  PubMed  Google Scholar 

  7. Fulop, T. et al. Aging, frailty and age-related diseases. Biogerontology 11, 547–563 (2010).

    Article  CAS  PubMed  Google Scholar 

  8. Isaacs, B. The challenge of geriatric medicine (Oxford University Press, 1997).

    Google Scholar 

  9. Health Council of the Netherlands. Health care for the elderly with multimorbidity. Publication no. 2008/01 (Health Council of the Netherlands, 2008).

  10. Lang, P. O., Michel, J. P. & Zekry, D. Frailty syndrome: a transitional state in a dynamic process. Gerontology 55, 539–549 (2009).

    Article  PubMed  Google Scholar 

  11. Fried, L. P. et al. Frailty in older adults: evidence for a phenotype. J. Gerontol. A Biol. Sci. Med. Sci. 56, M146–156 (2001).

    Article  CAS  PubMed  Google Scholar 

  12. Bandeen-Roche, K. et al. Phenotype of frailty: characterization in the women's health and aging studies. J. Gerontol. A Biol. Sci. Med. Sci. 61, 262–266 (2006).

    Article  PubMed  Google Scholar 

  13. Garonzik-Wang, J. M. et al. Frailty and delayed graft function in kidney transplant recipients. Arch. Surg. 147, 190–193 (2012).

    Article  PubMed  Google Scholar 

  14. Makary, M. A. et al. Frailty as a predictor of surgical outcomes in older patients. J. Am. Coll. Surg. 210, 901–908 (2010).

    Article  PubMed  Google Scholar 

  15. Yao, X. et al. Frailty is associated with impairment of vaccine-induced antibody response and increase in post-vaccination influenza infection in community-dwelling older adults. Vaccine 29, 5015–5021 (2011).

    Article  PubMed Central  PubMed  Google Scholar 

  16. Abadir, P. M. et al. Identification and characterization of a functional mitochondrial angiotensin system. Proc. Natl Acad. Sci. USA 108, 14849–14854 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Leng, S. X., Yang, H. & Walston, J. D. Decreased cell proliferation and altered cytokine production in frail older adults. Aging Clin. Exp. Res. 16, 249–252 (2004).

    Article  CAS  PubMed  Google Scholar 

  18. Varadhan, R. et al. Higher levels and blunted diurnal variation of cortisol in frail older women. J. Gerontol. A Biol. Sci. Med. Sci. 63, 190–195 (2008).

    Article  PubMed  Google Scholar 

  19. Gameiro, C. & Romao, F. Changes in the immune system during menopause and aging. Front. Biosci. (Elite Ed.) 2, 1299–1303 (2010).

    Article  Google Scholar 

  20. Gomez, C. R., Boehmer, E. D. & Kovacs, E. J. The aging innate immune system. Curr. Opin. Immunol. 17, 457–462 (2005).

    Article  CAS  PubMed  Google Scholar 

  21. Krabbe, K. S., Pedersen, M. & Bruunsgaard, H. Inflammatory mediators in the elderly. Exp. Gerontol. 39, 687–699 (2004).

    Article  CAS  PubMed  Google Scholar 

  22. Panda, A. et al. Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol. 30, 325–333 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Shaw, A. C., Joshi, S., Greenwood, H., Panda, A. & Lord, J. M. Aging of the innate immune system. Curr. Opin. Immunol. 22, 507–513 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Goronzy, J. J., Shao, L. & Weyand, C. M. Immune aging and rheumatoid arthritis. Rheum. Dis. Clin. North Am. 36, 297–310 (2010).

    Article  PubMed Central  PubMed  Google Scholar 

  25. Lindstrom, T. M. & Robinson, W. H. Rheumatoid arthritis: a role for immunosenescence? J. Am. Geriatr. Soc. 58, 1565–1575 (2010).

    Article  PubMed Central  PubMed  Google Scholar 

  26. Scullion, J. Tuberculosis and older people. Nurs. Older People 15, 23–27 (2003).

    Article  PubMed  Google Scholar 

  27. Frasca, D. & Blomberg, B. B. Aging affects human B cell responses. J. Clin. Immunol. 31, 430–435 (2011).

    Article  PubMed Central  PubMed  Google Scholar 

  28. Lee, N., Shin, M. S. & Kang, I. T-cell biology in aging, with a focus on lung disease. J. Gerontol. A Biol. Sci. Med. Sci. 67, 254–263 (2012).

    Article  CAS  PubMed  Google Scholar 

  29. Hakim, F. T. et al. Age-dependent incidence, time course, and consequences of thymic renewal in adults. J. Clin. Invest. 115, 930–939 (2005).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Geginat, J., Lanzavecchia, A. & Sallusto, F. Proliferation and differentiation potential of human CD8+ memory T-cell subsets in response to antigen or homeostatic cytokines. Blood 101, 4260–4266 (2003).

    Article  CAS  PubMed  Google Scholar 

  31. Broux, B., Markovic-Plese, S., Stinissen, P. & Hellings, N. Pathogenic features of CD4+CD28− T cells in immune disorders. Trends Mol. Med. 18, 446–453 (2012).

    Article  CAS  PubMed  Google Scholar 

  32. Weng, N. P., Akbar, A. N. & Goronzy, J. CD28− T cells: their role in the age-associated decline of immune function. Trends Immunol. 30, 306–312 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Vallejo, A. N. et al. Molecular basis for the loss of CD28 expression in senescent T cells. J. Biol. Chem. 277, 46940–46949 (2002).

    Article  CAS  PubMed  Google Scholar 

  34. Valenzuela, H. F. & Effros, R. B. Divergent telomerase and CD28 expression patterns in human CD4 and CD8 T cells following repeated encounters with the same antigenic stimulus. Clin. Immunol. 105, 117–125 (2002).

    Article  CAS  PubMed  Google Scholar 

  35. Koch, S. et al. Cytomegalovirus infection: a driving force in human T cell immunosenescence. Ann. NY Acad. Sci. 1114, 23–35 (2007).

    Article  CAS  PubMed  Google Scholar 

  36. van Leeuwen, E. M. et al. Emergence of a CD4+CD28− granzyme B+, cytomegalovirus-specific T cell subset after recovery of primary cytomegalovirus infection. J. Immunol. 173, 1834–1841 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Schirmer, M., Vallejo, A. N., Weyand, C. M. & Goronzy, J. J. Resistance to apoptosis and elevated expression of Bcl-2 in clonally expanded CD4+CD28− T cells from rheumatoid arthritis patients. J. Immunol. 161, 1018–1025 (1998).

    CAS  PubMed  Google Scholar 

  38. Vallejo, A. N., Schirmer, M., Weyand, C. M. & Goronzy, J. J. Clonality and longevity of CD4+CD28null T cells are associated with defects in apoptotic pathways. J. Immunol. 165, 6301–6307 (2000).

    Article  CAS  PubMed  Google Scholar 

  39. Vallejo, A. N. et al. Expansions of NK-like αβT cells with chronologic aging: novel lymphocyte effectors that compensate for functional deficits of conventional NK cells and T cells. Ageing Res. Rev. 10, 354–361 (2011).

    Article  CAS  PubMed  Google Scholar 

  40. Heyn, H. et al. Distinct DNA methylomes of newborns and centenarians. Proc. Natl Acad. Sci. USA 109, 10522–10527 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Liu, Y., Chen, Y. & Richardson, B. Decreased DNA methyltransferase levels contribute to abnormal gene expression in “senescent” CD4+CD28− T cells. Clin. Immunol. 132, 257–265 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Schmidt, D., Martens, P. B., Weyand, C. M. & Goronzy, J. J. The repertoire of CD4+ CD28− T cells in rheumatoid arthritis. Mol. Med. 2, 608–618 (1996).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Schmidt, D., Goronzy, J. J. & Weyand, C. M. CD4+CD7−CD28− T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity. J. Clin. Invest. 97, 2027–2037 (1996).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Bristol-Myers Squibb. Abatacept summary of product characteristics [online]

  45. Kremer, J. M. et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N. Engl. J. Med. 349, 1907–1915 (2003).

    Article  CAS  PubMed  Google Scholar 

  46. Arai, Y., Takayama, M., Abe, Y. & Hirose, N. Adipokines and aging. J. Atheroscler. Thromb. 18, 545–550 (2011).

    Article  CAS  PubMed  Google Scholar 

  47. Conde, J. et al. Adipokines: novel players in rheumatic diseases. Discov. Med. 15, 73–83 (2013).

    PubMed  Google Scholar 

  48. Gomez, R. et al. What's new in our understanding of the role of adipokines in rheumatic diseases? Nat. Rev. Rheumatol. 7, 528–536 (2011).

    Article  CAS  PubMed  Google Scholar 

  49. Olama, S. M., Senna, M. K. & Elarman, M. Synovial/serum leptin ratio in rheumatoid arthritis: the association with activity and erosion. Rheumatol. Int. 32, 683–690 (2012).

    Article  CAS  PubMed  Google Scholar 

  50. Matarese, G., Procaccini, C., De Rosa, V., Horvath, T. L. & La Cava, A. Regulatory T cells in obesity: the leptin connection. Trends Mol. Med. 16, 247–256 (2010).

    Article  CAS  PubMed  Google Scholar 

  51. Giles, J. T., Allison, M., Bingham, C. O. 3rd, Scott, W. M. Jr & Bathon, J. M. Adiponectin is a mediator of the inverse association of adiposity with radiographic damage in rheumatoid arthritis. Arthritis Rheum. 61, 1248–1256 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Matthews, S. J. & Lancaster, J. W. Urinary tract infections in the elderly population. Am. J. Geriatr. Pharmacother. 9, 286–309 (2011).

    Article  PubMed  Google Scholar 

  53. Meyer, K. C. The role of immunity and inflammation in lung senescence and susceptibility to infection in the elderly. Semin. Respir. Crit. Care Med. 31, 561–574 (2010).

    Article  PubMed  Google Scholar 

  54. Mori, T. & Leung, C. C. Tuberculosis in the global aging population. Infect. Dis. Clin. North Am. 24, 751–768 (2010).

    Article  PubMed  Google Scholar 

  55. Jefferson, T. et al. Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review. Lancet 366, 1165–1174 (2005).

    Article  CAS  PubMed  Google Scholar 

  56. Kumar, R. & Burns, E. A. Age-related decline in immunity: implications for vaccine responsiveness. Expert. Rev. Vaccines 7, 467–479 (2008).

    Article  PubMed  Google Scholar 

  57. Lang, P. O., Govind, S., Mitchell, W. A., Siegrist, C. A. & Aspinall, R. Vaccine effectiveness in older individuals: what has been learned from the influenza-vaccine experience. Ageing Res. Rev. 10, 389–395 (2011).

    Article  CAS  PubMed  Google Scholar 

  58. Lang, P. O. et al. Effectiveness of influenza vaccine in aging and older adults: comprehensive analysis of the evidence. Clin. Interv. Aging 7, 55–64 (2012).

    Article  PubMed Central  PubMed  Google Scholar 

  59. McElhaney, J. E. Influenza vaccine responses in older adults. Ageing Res. Rev. 10, 379–388 (2011).

    Article  CAS  PubMed  Google Scholar 

  60. Fujihashi, K. & Kiyono, H. Mucosal immunosenescence: new developments and vaccines to control infectious diseases. Trends Immunol. 30, 334–343 (2009).

    Article  CAS  PubMed  Google Scholar 

  61. Giuliano, S., Ohanna, M., Ballotti, R. & Bertolotto, C. Advances in melanoma senescence and potential clinical application. Pigment Cell Melanoma Res. 24, 295–308 (2011).

    Article  CAS  PubMed  Google Scholar 

  62. Lasithiotakis, K. G., Petrakis, I. E. & Garbe, C. Cutaneous melanoma in the elderly: epidemiology, prognosis and treatment. Melanoma Res. 20, 163–170 (2010).

    PubMed  Google Scholar 

  63. Finkel, T., Serrano, M. & Blasco, M. A. The common biology of cancer and ageing. Nature 448, 767–774 (2007).

    Article  CAS  PubMed  Google Scholar 

  64. de Vlam, K. et al. Detection and identification of antinuclear autoantibodies in the serum of normal blood donors. Clin. Exp. Rheumatol. 11, 393–397 (1993).

    CAS  PubMed  Google Scholar 

  65. Borchers, A. T. & Gershwin, M. E. Giant cell arteritis: a review of classification, pathophysiology, geoepidemiology and treatment. Autoimmun. Rev. 11, A544–A554 (2012).

    Article  PubMed  Google Scholar 

  66. Crowson, C. S. et al. The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases. Arthritis Rheum. 63, 633–639 (2011).

    Article  PubMed Central  PubMed  Google Scholar 

  67. Fujii, H., Shao, L., Colmegna, I., Goronzy, J. J. & Weyand, C. M. Telomerase insufficiency in rheumatoid arthritis. Proc. Natl Acad. Sci. USA 106, 4360–4365 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Weyand, C. M., Fujii, H., Shao, L. & Goronzy, J. J. Rejuvenating the immune system in rheumatoid arthritis. Nat. Rev. Rheumatol. 5, 583–588 (2009).

    Article  CAS  PubMed  Google Scholar 

  69. Koetz, K. et al. T cell homeostasis in patients with rheumatoid arthritis. Proc. Natl Acad. Sci. USA 97, 9203–9208 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Goronzy, J. J. & Weyand, C. M. Immune aging and autoimmunity. Cell. Mol. Life Sci. 69, 1615–1623 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Colmegna, I. et al. Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenitor cells in rheumatoid arthritis. Arthritis Rheum. 58, 990–1000 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Shao, L. et al. Deficiency of the DNA repair enzyme ATM in rheumatoid arthritis. J. Exp. Med. 206, 1435–1449 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Kohler, S. & Thiel, A. Life after the thymus: CD31+ and CD31− human naive CD4+ T-cell subsets. Blood 113, 769–774 (2009).

    Article  CAS  PubMed  Google Scholar 

  74. Lee, W. W., Yang, Z. Z., Li, G., Weyand, C. M. & Goronzy, J. J. Unchecked CD70 expression on T cells lowers threshold for T cell activation in rheumatoid arthritis. J. Immunol. 179, 2609–2615 (2007).

    Article  CAS  PubMed  Google Scholar 

  75. Singh, K., Colmegna, I., He, X., Weyand, C. M. & Goronzy, J. J. Synoviocyte stimulation by the LFA-1–intercellular adhesion molecule-2–Ezrin–Akt pathway in rheumatoid arthritis. J. Immunol. 180, 1971–1978 (2008).

    Article  CAS  PubMed  Google Scholar 

  76. Mavragani, C. P. & Moutsopoulos, H. M. Rheumatoid arthritis in the elderly. Exp. Gerontol. 34, 463–471 (1999).

    Article  CAS  PubMed  Google Scholar 

  77. Tutuncu, Z. & Kavanaugh, A. Rheumatic disease in the elderly: rheumatoid arthritis. Clin. Geriatr. Med. 21, 513–525 (2005).

    Article  PubMed  Google Scholar 

  78. van Schaardenburg, D. & Breedveld, F. C. Elderly-onset rheumatoid arthritis. Semin. Arthritis Rheum. 23, 367–378 (1994).

    Article  CAS  PubMed  Google Scholar 

  79. Villa-Blanco, J. I. & Calvo-Alen, J. Elderly onset rheumatoid arthritis: differential diagnosis and choice of first-line and subsequent therapy. Drugs Aging 26, 739–750 (2009).

    Article  CAS  PubMed  Google Scholar 

  80. Kermani, T. A. & Warrington, K. J. Polymyalgia rheumatica. Lancet 381, 63–72 (2013).

    Article  PubMed  Google Scholar 

  81. Chen, D. Y. et al. Proinflammatory cytokine profiles of patients with elderly-onset rheumatoid arthritis: a comparison with younger-onset disease. Gerontology 55, 250–258 (2009).

    Article  CAS  PubMed  Google Scholar 

  82. Glennas, A., Kvien, T. K., Andrup, O., Karstensen, B. & Munthe, E. Recent onset arthritis in the elderly: a 5 year longitudinal observational study. J. Rheumatol. 27, 101–108 (2000).

    CAS  PubMed  Google Scholar 

  83. van der Heijde, D. M. et al. Older versus younger onset rheumatoid arthritis: results at onset and after 2 years of a prospective followup study of early rheumatoid arthritis. J. Rheumatol. 18, 1285–1289 (1991).

    CAS  PubMed  Google Scholar 

  84. Gabriel, S. E. & Michaud, K. Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res. Ther. 11, 229 (2009).

    Article  PubMed Central  PubMed  Google Scholar 

  85. 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 

  86. Maradit-Kremers, H., Nicola, P. J., Crowson, C. S., Ballman, K. V. & Gabriel, S. E. Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum. 52, 722–732 (2005).

    Article  PubMed  Google Scholar 

  87. Nicola, P. J. et al. The risk of congestive heart failure in rheumatoid arthritis: a population-based study over 46 years. Arthritis Rheum. 52, 412–420 (2005).

    Article  PubMed  Google Scholar 

  88. Madjid, M. & Willerson, J. T. Inflammatory markers in coronary heart disease. Br. Med. Bull. 100, 23–38 (2011).

    Article  CAS  PubMed  Google Scholar 

  89. Liao, K. P. & Solomon, D. H. Traditional cardiovascular risk factors, inflammation and cardiovascular risk in rheumatoid arthritis. Rheumatology (Oxford) 52, 45–52 (2013).

    Article  Google Scholar 

  90. Smitten, A. L., Simon, T. A., Hochberg, M. C. & Suissa, S. A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res. Ther. 10, R45 (2008).

    Article  PubMed Central  PubMed  Google Scholar 

  91. Baecklund, E. et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum. 54, 692–701 (2006).

    Article  PubMed  Google Scholar 

  92. Niccoli, T. & Partridge, L. Ageing as a risk factor for disease. Curr. Biol. 22, R741–R752 (2012).

    Article  CAS  PubMed  Google Scholar 

  93. Askling, J. & Bongartz, T. Malignancy and biologic therapy in rheumatoid arthritis. Curr. Opin. Rheumatol. 20, 334–339 (2008).

    Article  CAS  PubMed  Google Scholar 

  94. Doran, M. F., Crowson, C. S., Pond, G. R., O'Fallon, W. M. & Gabriel, S. E. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 46, 2287–2293 (2002).

    Article  PubMed  Google Scholar 

  95. De Keyser, F. Choice of biologic therapy for patients with rheumatoid arthritis: the infection perspective. Curr. Rheumatol. Rev. 7, 77–87 (2011).

    Article  CAS  Google Scholar 

  96. Salliot, C., Dougados, M. & Gossec, L. Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials. Ann. Rheum. Dis. 68, 25–32 (2009).

    Article  CAS  PubMed  Google Scholar 

  97. Crowson, C. S., Hoganson, D. D., Fitz-Gibbon, P. D. & Matteson, E. L. Development and validation of a risk score for serious infection in patients with rheumatoid arthritis. Arthritis Rheum. 64, 2847–2855 (2012).

    Article  PubMed Central  PubMed  Google Scholar 

  98. Seitz, C. S., Berens, N., Brocker, E. B. & Trautmann, A. Leg ulceration in rheumatoid arthritis—an underreported multicausal complication with considerable morbidity: analysis of thirty-six patients and review of the literature. Dermatology 220, 268–273 (2010).

    Article  PubMed  Google Scholar 

  99. Summers, G. D., Deighton, C. M., Rennie, M. J. & Booth, A. H. Rheumatoid cachexia: a clinical perspective. Rheumatology (Oxford) 47, 1124–1131 (2008).

    Article  CAS  Google Scholar 

  100. Munro, R. & Capell, H. Prevalence of low body mass in rheumatoid arthritis: association with the acute phase response. Ann. Rheum. Dis. 56, 326–329 (1997).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. Chen, Y. M., Chen, L. K., Lan, J. L. & Chen, D. Y. Geriatric syndromes in elderly patients with rheumatoid arthritis. Rheumatology (Oxford) 48, 1261–1264 (2009).

    Article  Google Scholar 

  102. Ziade, N., Jougla, E. & Coste, J. Population-level influence of rheumatoid arthritis on mortality and recent trends: a multiple cause-of-death analysis in France, 1970–2002. J. Rheumatol. 35, 1950–1957 (2008).

    PubMed  Google Scholar 

  103. Fraenkel, L., Rabidou, N. & Dhar, R. Are rheumatologists' treatment decisions influenced by patients' age? Rheumatology (Oxford) 45, 1555–1557 (2006).

    Article  CAS  Google Scholar 

  104. Schmajuk, G. et al. Treatment of older adult patients diagnosed with rheumatoid arthritis: improved but not optimal. Arthritis Rheum. 57, 928–934 (2007).

    Article  PubMed  Google Scholar 

  105. Radovits, B. J., Fransen, J., Eijsbouts, A., van Riel, P. L. & Laan, R. F. Missed opportunities in the treatment of elderly patients with rheumatoid arthritis. Rheumatology (Oxford) 48, 906–910 (2009).

    Article  Google Scholar 

  106. Radovits, B. J. et al. Influence of age on the outcome of antitumour necrosis factor alpha therapy in rheumatoid arthritis. Ann. Rheum. Dis. 68, 1470–1473 (2009).

    Article  CAS  PubMed  Google Scholar 

  107. Bathon, J. M. et al. Safety and efficacy of etanercept treatment in elderly subjects with rheumatoid arthritis. J. Rheumatol. 33, 234–243 (2006).

    CAS  PubMed  Google Scholar 

  108. Fleischmann, R. M. et al. Response to etanercept (Enbrel) in elderly patients with rheumatoid arthritis: a retrospective analysis of clinical trial results. J. Rheumatol. 30, 691–696 (2003).

    CAS  PubMed  Google Scholar 

  109. Lurati, A., Marrazza, M., Angela, K. & Scarpellini, M. Safety of etanercept in elderly subjects with rheumatoid arthritis. Biologics 4, 1–4 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  110. Genevay, S. et al. Tolerance and effectiveness of anti-tumor necrosis factor alpha therapies in elderly patients with rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 57, 679–685 (2007).

    Article  PubMed  Google Scholar 

  111. Galloway, J. B. et al. Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly. Rheumatology (Oxford) 50, 124–131 (2011).

    Article  CAS  Google Scholar 

  112. Schneeweiss, S. et al. Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis. Arthritis Rheum. 56, 1754–1764 (2007).

    Article  CAS  PubMed  Google Scholar 

  113. Dotan, E., Browner, I., Hurria, A. & Denlinger, C. Challenges in the management of older patients with colon cancer. J. Natl Compr. Canc. Netw. 10, 213–224 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  114. Pallis, A. G. & Scarci, M. Are we treating enough elderly patients with early stage non-small cell lung cancer? Lung Cancer 74, 149–154 (2011).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The inspiration for this article came from the Academy of Immunology for Clinicians, Belgium, Spring Lecture Sessions on ageing and immune-mediated inflammatory disorders. The authors thank H. Van de Keere (10A, Maldegem, Belgium) and P. Leventhal (4Clinics, Paris, France) for English-language editorial assistance.

Author information

Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, UMCG, University of Groningen, Groningen, 9700 RB, The Netherlands

    Annemieke M. H. Boots

  2. Department of Internal Medicine, VU University Medical Centre, Amsterdam, 1007 MB, The Netherlands

    Andrea B. Maier

  3. Hasselt University, Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, B-3590, Belgium

    Piet Stinissen

  4. de Duve Institute, Université Catholique de Louvain, Brussels, B-1200, Belgium

    Pierre Masson

  5. Department of Musculoskeletal Sciences, Division of Rheumatology, University Hospitals Leuven, Leuven, B-3000, Belgium

    Rik J. Lories

  6. Department of Rheumatology, Ghent University, Ghent, B-9000, Belgium

    Filip De Keyser

Authors
  1. Annemieke M. H. Boots
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  2. Andrea B. Maier
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  3. Piet Stinissen
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  4. Pierre Masson
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  5. Rik J. Lories
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  6. Filip De Keyser
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Contributions

All authors contributed to researching data for the article, discussion of content and review/editing of the manuscript before submission. F. De Keyser wrote the article.

Corresponding author

Correspondence to Filip De Keyser.

Ethics declarations

Competing interests

P. Masson declares that he has received speakers fees from Abbott (Abbvie); R. Lories declares that he has received speakers or consultancy fees from Abbott (Abbvie), Boehringer Ingelheim, Celgene, Jansen, Merck and Pfizer, and has received research support from Abbott, Celgene, and Pfizer. F. De Keyser declares that he has received consultancy fees from Abbott (Abbvie), AstraZeneca, GSK, MSD, Pfizer and Roche. A. M. H. Boots, A. B. Maier and P. Stinissen declare no competing interests.

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Boots, A., Maier, A., Stinissen, P. et al. The influence of ageing on the development and management of rheumatoid arthritis. Nat Rev Rheumatol 9, 604–613 (2013). https://doi.org/10.1038/nrrheum.2013.92

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