Drugs & Aging

, Volume 22, Issue 10, pp 809–822 | Cite as

Management Issues with Elderly-Onset Rheumatoid Arthritis

An Update
  • Ignazio Olivieri
  • Carlo Palazzi
  • Giovanni Peruz
  • Angela Padula
Leading Article

Abstract

Elderly-onset rheumatoid arthritis (EORA) is defined as rheumatoid arthritis (RA) starting at >60 years of age. EORA is characterised by a lower female/male ratio compared with RA in younger patients and it more frequently has an acute onset accompanied by constitutional symptoms. Two incompletely overlapping subsets of RA have been recognised: one exhibits the classical RA clinical picture while the other has a polymyalgia rheumatica-like appearance, characterised by shoulder involvement, absence of rheumatoid factor and, usually, by a nonerosive course. Identification of anti-cyclic citrullinated peptide antibodies is useful for distinguishing the latter subset from true polymyalgia rheumatica. Elderly-onset spondyloarthritis, crystal-related arthritis, remitting seronegative symmetrical synovitis with pitting oedema syndrome and hepatitis C virus-related arthritis must also be considered in the differential diagnosis. EORA treatment requires prudence because of the increase in age-related risks pertaining principally to the renal, cardiovascular and gastrointestinal systems. No groups of molecules usually employed for RA therapy in younger subjects (analgesics, NSAIDs, corticosteroids, disease-modifying antirheumatic drugs, anticytokine drugs) can be excluded a priori from the treatment of EORA patients. Nevertheless, the risk/benefit ratio relating to their use must be accurately evaluated for every single patient. Recently marketed compounds such as leflunomide and tumour necrosis factor-α antagonists have also increased the therapeutic opportunities for aged RA patients.

References

  1. 1.
    van Schaardenburg D, Breedveld FC. Elderly-onset rheumatoid arthritis. Semin Arthritis Rheum 1994; 23: 367–78PubMedGoogle Scholar
  2. 2.
    Caroit M. Polyarthritis in the elderly [in German]. Z Gerontol 1993; 26: 13–6PubMedGoogle Scholar
  3. 3.
    Inoue K, Shichikawa K, Nishioka J, et al. Older age onset rheumatoid arthritis with or without osteoarthritis. Ann Rheum Dis 1987; 46: 908–11PubMedGoogle Scholar
  4. 4.
    Bajocchi G, La Corte R, Locaputo A, et al. Elderly onset rheumatoid arthritis: clinical aspects. Clin Exp Rheumatol 2000; 18Suppl. 20: 49–50Google Scholar
  5. 5.
    Papadopoulos IA, Katsimbri P, Alamanos Y, et al. Early rheumatoid arthritis patients: relationship of age. Rheumatol Int 2003; 23: 70–4PubMedGoogle Scholar
  6. 6.
    Deal CL, Meenan RF, Goldenberg DL, et al. The clinical features of elderly-onset rheumatoid arthritis: a comparison with younger-onset disease of similar duration. Arthritis Rheum 1985; 28: 987–94PubMedGoogle Scholar
  7. 7.
    Terkeltaub R, Esdaile J, Decary F, et al. A clinical study of older age rheumatoid arthritis with comparison of a younger onset group. J Rheumatol 1983; 10: 418–24PubMedGoogle Scholar
  8. 8.
    van Schaardenburg D, Lagaay AM, Otten HG, et al. The relation between class-specific rheumatoid factor and age in the general population. Br J Rheumatol 1993; 32: 546–9PubMedGoogle Scholar
  9. 9.
    Ferraccioli GF, Cavalieri F, Mercandati M, et al. Clinical features, scintiscan characteristics and X-ray progression of late onset rheumatoid arthritis. Clin Exp Rheumatol 1984; 2: 157–61PubMedGoogle Scholar
  10. 10.
    Van der Heijde DM, van Riel PL, van Leeuwen MA, et al. Older versus younger onset rheumatoid arthritis: results at onset and after 2 years of a prospective follow-up study of early rheumatoid arthritis. J Rheumatol 1991; 18: 1285–9PubMedGoogle Scholar
  11. 11.
    Fleming A, Crown JM, Corbett M. Prognostic value of early features in rheumatoid disease. BMJ 1976; 1: 1243–5PubMedGoogle Scholar
  12. 12.
    Scott DL, Symmons DP, Coulton BL, et al. Long-term outcome of treating rheumatoid arthritis: results after 20 years. Lancet 1987; I: 1108–11Google Scholar
  13. 13.
    van Zeben D, Hazes JM, Zwinderman AH, et al. Association of HLA-DR4 with a more progressive disease course in patients with rheumatoid arthritis: results of a follow-up study. Arthritis Rheum 1991; 34: 822–30PubMedGoogle Scholar
  14. 14.
    Terkeltaub R, Decary F, Esdaile J, et al. An immunogenetic clinical study of older age onset rheumatoid arthritis. J Rheumatol 1984; 11: 147–9PubMedGoogle Scholar
  15. 15.
    Hazes JM, Dijkmans BA, Hoevers JM, et al. DR4 prevalence related to the age at disease onset in female patients with rheumatoid arthritis. Ann Rheum Dis 1989; 48: 406–8PubMedGoogle Scholar
  16. 16.
    Yukioka M, Wakitani S, Murata N, et al. Elderly-onset rheumatoid arthritis and its association with HLA-DRB1 alleles in Japanese. Br J Rheumatol 1998; 17: 98–101Google Scholar
  17. 17.
    Gonzalez-Gay MA, Hajeer AH, Dababneh A, et al. Seronegative rheumatoid arthritis in elderly and polymyalgia rheumatica have similar patterns of HLA association. J Rheumatol 2001; 28: 122–5PubMedGoogle Scholar
  18. 18.
    Mavragani CP, Moutsopoulos HM. Rheumatoid arthritis in the elderly. Exp Gerontol 1999; 34: 463–71PubMedGoogle Scholar
  19. 19.
    Uhlig T, Kvien TK, Glennas A, et al. The incidence and severity of rheumatoid arthritis, results from a county register in Oslo, Norway. J Rheumatol 1998; 25: 1078–84PubMedGoogle Scholar
  20. 20.
    Kvien TK, Glennas A, Knuderod OG, et al. The prevalence and severity of rheumatoid arthritis in Oslo: results from a county register and a population survey. Scand J Rheumatol 1997; 26: 412–8PubMedGoogle Scholar
  21. 21.
    Symmons DPM, Barrett EM, Bankhead C, et al. The incidence of rheumatoid arthritis in the United Kingdom: results from the Norfolk Arthritis Register. Br J Rheumatol 1994; 33: 735–9PubMedGoogle Scholar
  22. 22.
    Laiho K, Tuomilehto J, Tilvis R. Prevalence of rheumatoid arthritis and musculoskeletal diseases in the elderly population. Rheumatol Int 2001; 20: 85–7PubMedGoogle Scholar
  23. 23.
    Rasch EK, Hirsch R, Paulosa-Ram R, et al. Prevalence of rheumatoid arthritis in persons 60 years of age and older in the United States: effect of different methods of case classification. Arthritis Rheum 2003; 48: 917–26PubMedGoogle Scholar
  24. 24.
    Bergstrom G, Bjelle A, Sundh V, et al. Joint disorders at age 70, 75 and 79 years: a cross-sectional comparison. Br J Rheumatol 1986; 25: 333–41PubMedGoogle Scholar
  25. 25.
    van Schaardenburg D, Lagaay AM, Breedveld FC, et al. Rheumatoid arthritis in a population of persons aged 85 years and over. Br J Rheumatol 1993; 32: 104–9PubMedGoogle Scholar
  26. 26.
    Healey LA. Polymyalgia rheumatica and seronegative rheumatoid arthritis may be the same entity. J Rheumatol 1992; 19: 270–2PubMedGoogle Scholar
  27. 27.
    Salvarani C, Cantini F, Olivieri I. Distal musculoskeletal manifestations in polymyalgia rheumatica. Clin Exp Rheumatol 2000; 18Suppl. 20: 51–2Google Scholar
  28. 28.
    Lopez-Hoyos M, Ruiz de Alegria C, Blanco R, et al. Clinical utility of anti-CCP antibodies in the differential diagnosis of elderly-onset rheumatoid arthritis and polymyalgia rheumatica. Rheumatology (Oxford) 2004; 43: 655–7Google Scholar
  29. 29.
    Lange U, Piegsa M, Teichmann J, et al. Ultrasonography of the glenohumeral joints: a helpful instrument in differentiation in elderly onset rheumatoid arthritis and polymyalgia rheumatica. Rheumatol Int 2000; 19: 185–9PubMedGoogle Scholar
  30. 30.
    Pavlica P, Barozzi L, Salvarani C, et al. Magnetic resonance imaging in the diagnosis of PMR. Clin Exp Rheumatol 2000; 18Suppl. 20: 38–9Google Scholar
  31. 31.
    Cantini F, Salvarani C, Olivieri I, et al. Shoulder ultrasonography in the diagnosis of polymyalgia rheumatica: a case control study. J Rheumatol 2001; 28: 1049–55PubMedGoogle Scholar
  32. 32.
    Cantini F, Salvarani C, Niccoli L, et al. Fat suppression magnetic resonance imaging in shoulders of patients with polymyalgia rheumatica. J Rheumatol 2004; 31: 120–4PubMedGoogle Scholar
  33. 33.
    Olivieri I, Salvarani C, Cantini F. RS3PE syndrome: an over-view. Clin Exp Rheumatol 2000; 18Suppl. 20: 53–5Google Scholar
  34. 34.
    Cantini F, Salvarani C, Olivieri I, et al. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome: a prospective follow-up and magnetic resonance study. Ann Rheum Dis 1999; 58: 230–6PubMedGoogle Scholar
  35. 35.
    Dubost JJ, Sauvezie B. Late onset peripheral spondyloar-thropathy. J Rheumatol 1989; 16: 1214–7PubMedGoogle Scholar
  36. 36.
    Olivieri I, Salvarani C, Cantini F, et al. Ankylosing spondylitis and undifferentiated spondyloarthropathies: a clinical review and description of a disease subset with older age at onset. Curr Opin Rheumatol 2001; 13: 280–4PubMedGoogle Scholar
  37. 37.
    Dougados M, van der Linden S, Juhlin R, et al. The European Spondyloarthropathy Study Group preliminary criteria for the classification of spondyloarthropathy. Arthritis Rheum 1991; 34: 1218–27PubMedGoogle Scholar
  38. 38.
    Palazzi C, Olivieri I, Petricca A, et al. Rheumatoid arthritis or psoriatic symmetric polyarthritis? A difficult differential diagnosis. Clin Exp Rheumatol 2002; 20: 3–4PubMedGoogle Scholar
  39. 39.
    Salvarani C, Cantini F, Olivieri I, et al. Distal extremity swelling with pitting edema in psoriatic arthritis: evidence of two pathological mechanisms. J Rheumatol 1999; 26: 1831–4PubMedGoogle Scholar
  40. 40.
    Kiely PD, Joseph AE, Mortimer PS, et al. Upper limb lymphedema associated with polyarthritis of rheumatoid type. J Rheumatol 1994; 21: 1043–5PubMedGoogle Scholar
  41. 41.
    Olivieri I, Barozzi L, Padula A. Enthesiopathy: clinical manifestations, imaging and treatment. Ballieres Clin Rheumatol 1998; 12: 665–81Google Scholar
  42. 42.
    Olivieri I, Salvarani C, Cantini F, et al. Fast spin echo T2-weighted sequences with fat saturation in dactylitis of spondyloarthritis. Arthritis Rheum 2002; 46: 2964–7PubMedGoogle Scholar
  43. 43.
    Salvarani C, Olivieri I, Cantini F, et al. Psoriatic arthritis. Curr Opin Rheumatol 1998; 10: 299–305PubMedGoogle Scholar
  44. 44.
    Van der Cruyssens B, Hoffman IE, Zmierczak H, et al. Anticitrullinated peptide antibodies may occur in patients with psoriatic arthritis. Ann Rheum Dis 2005; 64: 1145–9Google Scholar
  45. 45.
    Bogliolo L, Alpini C, Caporali R, et al. Antibodies to cyclic citrullinated peptides in psoriatic arthritis. J Rheumatol 2005; 32: 511–5PubMedGoogle Scholar
  46. 46.
    Levinson DJ, Becker MA. Clinical gout and the pathogenesis of hyperuricemia. In: McCarty DJ, Koopman WJ, editors. Arthritis and allied conditions. 12th ed. Malvern (PA): Lea and Febiger, 1993: 1773–805Google Scholar
  47. 47.
    Lawrence MR, McCarty DJ. Calcium pyrophosphate crystal deposition disease; pseudogout; articular chondrocalcinosis. In: McCarty DJ, Koopman WJ, editors. Arthritis and allied conditions. 12th ed. Malvern (PA): Lea and Febiger, 1993: 1835–55Google Scholar
  48. 48.
    Palazzi C, Olivieri I, Cacciatore P, et al. Difficulties in the differential diagnosis between primitive rheumatic diseases and hepatitis C virus-related disorders. Clin Exp Rheumatol 2005; 23: 2–6PubMedGoogle Scholar
  49. 49.
    Bombardieri M, Alessandri C, Labbadia G, et al. Role of anti-cyclic citrullinated peptide antibodies in discriminating patients with rheumatoid arthritis from patients with chronic hepatitis C infection-associated polyarticular involvement. Arthritis Res Ther 2004; 6: R137–41PubMedGoogle Scholar
  50. 50.
    Pines A, Kaplinsky N, Olchovsky D, et al. Rheumatoid arthritislike syndrome: a presenting symptom of malignancy: report of 3 cases and review of the literature. Eur J Rheumatol Inflamm 1984; 7: 51–5PubMedGoogle Scholar
  51. 51.
    Caldwell DS, McCallum RM. Rheumatologic manifestations of cancer. Med Clin North Am 1986; 70: 385–417PubMedGoogle Scholar
  52. 52.
    Mok CC, Kwan YK. Rheumatoid like polyarthritis as a presenting feature of metastatic carcinoma: a case presentation and review of the literature. Clin Rheumatol 2003; 22: 353–4PubMedGoogle Scholar
  53. 53.
    Stummvoll GH, Aringer M, Machold KP, et al. Cancer polyarthritis resembling rheumatoid arthritis as a first sign of hidden neoplasms: report of two cases and review of the literature. Scand J Rheumatol 2001; 30: 40–4PubMedGoogle Scholar
  54. 54.
    de Jong Z, Vliet Vieland TPM. Safety of exercise in patients with rheumatoid arthritis. Curr Opin Rheumatol 2005; 17: 177–82PubMedGoogle Scholar
  55. 55.
    Li LC, Iversen MD. Outcomes of patients with rheumatoid arthritis receiving rehabilitation. Curr Opin Rheumatol 2005; 17: 172–6PubMedGoogle Scholar
  56. 56.
    Snow MH, Mikula TR. Rheumatoid arthritis and cardiovascular disease: the role of systemic inflammation and evolving strategies of prevention. Curr Opin Rheumatol 2005; 17: 234–41PubMedGoogle Scholar
  57. 57.
    Huusko TM, Korpela M, Karppi P, et al. Threefold increased risk of hip fractures with rheumatoid arthritis in Central Finland. Ann Rheum Dis 2001; 60: 521–2PubMedGoogle Scholar
  58. 58.
    Haugeberg G, Orstavik RE, Uhlig T, et al. Bone loss in patients with rheumatoid arthritis: results from a population-based cohort of 366 patients followed up for two years. Arthritis Rheum 2002; 46: 1720–8PubMedGoogle Scholar
  59. 59.
    Finckh A, Iversen M, Liang MH. The exercise prescription in rheumatoid arthritis: primum non nocere. Arthritis Rheum 2003; 48: 2393–5PubMedGoogle Scholar
  60. 60.
    de Jong Z, Munneke M, Lems WF, et al. Slowing of bone loss in patients with rheumatoid arthritis by long-term high-intensity exercise: results of a randomized, controlled trial. Arthritis Rheum 2004; 50: 1066–76PubMedGoogle Scholar
  61. 61.
    American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum 2002; 46: 328–46Google Scholar
  62. 62.
    Studenski SA, Ward MM. Pharmacology and the elderly. In: Harris Jr ED, Budd RC, Firestein GS, et al., editors. Kelley’s textbook of rheumatology. 7th ed. Philadelphia (PA): Elsevier Saunders, 2005: 961–6Google Scholar
  63. 63.
    Walker J, Wynne H. The frequency and severity of adverse drug reactions in older people. Age Ageing 1994; 23: 255–9PubMedGoogle Scholar
  64. 64.
    Pescott LF. Paracetamol: past, present and future. Am J Ther 2000; 7: 143–7Google Scholar
  65. 65.
    Rahme E, Pettitt D, LeLorier J. Determinants and sequelae associated with utililization of acetaminophen versus traditional nonsteroidal antiinflammatory drugs in an elderly population. Arthritis Rheum 2002; 46: 3046–54PubMedGoogle Scholar
  66. 66.
    Fored CM, Ejerblad E, Lindblad P, et al. Acetaminophen, aspirin, and chronic renal failure. N Engl J Med 2001; 345: 1801–8PubMedGoogle Scholar
  67. 67.
    Gabriel SE, Jaakkimainen L, Bombardier C. Risk of serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs: a meta-analysis. Ann Intern Med 1991; 115: 787–96PubMedGoogle Scholar
  68. 68.
    Singh G, Ramey DR, Morfeld D, et al. Gastrointestinal tract complication of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis: a prospective observational cohort study. Arch Intern Med 1996; 156: 1530–6PubMedGoogle Scholar
  69. 69.
    Lanza FL. A guideline for the treatment and prevention of NSAID-induced ulcers. Members of the Ad Hoc Committee on Practice Parameters of the American College of Gastroen-terology. Am J Gastroenterol 1998; 93: 2037–46PubMedGoogle Scholar
  70. 70.
    Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs: a randomized, double-blind, placebo controlled trial. Ann Intern Med 1995; 123: 241–9PubMedGoogle Scholar
  71. 71.
    Simon LS, Hatoum TH, Bittman RM, et al. Risk factors for serious nonsteroidal-induced gastrointestinal complications: regression analysis of the MUCOSA trial. Fam Med 1996; 28: 204–10PubMedGoogle Scholar
  72. 72.
    Hooper L, Brown TJ, Elliott R, et al. The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: systematic review. BMJ 2004; 329(7472): 366–8. Epub 2004 Oct 8Google Scholar
  73. 73.
    Topol EJ. Arthritis medicines and cardiovascular events: ‘house of coxibs’. JAMA 2005; 293: 366–8PubMedGoogle Scholar
  74. 74.
    Chan FK, To KF, Wu JC, et al. Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomized trial. Lancet 2002; 359: 9–13PubMedGoogle Scholar
  75. 75.
    Patrono C, Dunn MJ. The clinical significance of inhibition of renal prostaglandin synthesis. Kidney Int 1987; 32: 1–12PubMedGoogle Scholar
  76. 76.
    Gurwitz JH, Avorn J, Bohn RL, et al. Initiation of antihypertensive treatment during nonsteroidal anti-inflammatory drug therapy. JAMA 1994; 272: 781–6PubMedGoogle Scholar
  77. 77.
    Hoppmann RA, Peden JG, Ober SK. Central nervous system side effects of nonsteroidal anti-inflammatory drugs: aseptic meningitis, psychosis, and cognitive dysfunction. Arch Intern Med 1991; 151: 1309–13PubMedGoogle Scholar
  78. 78.
    Blackburn D, Hux J, Mamdasni M. Quantification of the risk of corticoid-induced diabetes mellitus among the elderly. J Gen Intern Med 2002; 17: 717–20PubMedGoogle Scholar
  79. 79.
    Wei L, MacDonald TM, Walker BR. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med 2004; 141: 764–70PubMedGoogle Scholar
  80. 80.
    Souverein PC, Berard A, Van Staa TP, et al. Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case-control study. Heart 2004; 90: 859–65PubMedGoogle Scholar
  81. 81.
    Pattern SB. Exogenous corticosteroids and major depression in the general population. J Psychosom Res 2000; 49: 447–9Google Scholar
  82. 82.
    Belanoff JK, Gross K, Yager A, et al. Corticosteroids and cognition. J Psychiatr Res 2001; 35: 127–45PubMedGoogle Scholar
  83. 83.
    Gotzsche PC, Johansen HK. Meta-analysis of short-term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis. BMJ 1998; 316: 811–8PubMedGoogle Scholar
  84. 84.
    Kirwan JR. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. N Engl J Med 1995; 333: 142–6PubMedGoogle Scholar
  85. 85.
    Hickling P, Jacoby RK, Kirwan JR, et al. Joint destruction after glucocorticoids are withdrawn in early rheumatoid arthritis. Br J Rheumatol 1998; 37: 930–6PubMedGoogle Scholar
  86. 86.
    Van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med 2002; 136: 1–12PubMedGoogle Scholar
  87. 87.
    McDougall R, Sibley J, Haga M, et al. Outcome in patients with rheumatoid arthritis receiving prednisone compared to matched controls. J Rheumatol 1994; 21: 1207–13PubMedGoogle Scholar
  88. 88.
    Paulus HE, Di Primeo D, Sanda M, et al. Progression of radiographic joint erosion during low dose corticosteroid treatment of rheumatoid arthritis. J Rheumatol 2000; 27: 1632–7PubMedGoogle Scholar
  89. 89.
    Capell HA, Madhok R, Hunter JA, et al. Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial. Ann Rheum Dis 2004; 63: 797–803PubMedGoogle Scholar
  90. 90.
    American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum 2001; 44: 1496–503Google Scholar
  91. 91.
    Iglehart III IW, Sutton JD, Bender JC, et al. Intravenous pulsed steroid: a comparative dose study. J Rheumatol 1990; 17: 159–62PubMedGoogle Scholar
  92. 92.
    Weiss MM. Corticosteroids in rheumatoid arthritis. Semin Arthritis Rheum 1989; 19: 9–21PubMedGoogle Scholar
  93. 93.
    Rau R, Herborn G. Benefit and risk of methotrexate treatment in rheumatoid arthritis. Clin Exp Rheumatol 2004; 22Suppl. 35: 83–94Google Scholar
  94. 94.
    Lambert CM, Sandhu S, Lochhead A, et al. Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: a randomised, controlled trial. Arthritis Rheum 2004; 50: 364–71PubMedGoogle Scholar
  95. 95.
    Hirshberg B, Muszkat M, Schlesinger O, et al. Safety of low dose methotrexate in elderly patients with rheumatoid arthritis. Postgrad Med J 2000; 76: 787–9PubMedGoogle Scholar
  96. 96.
    Dahl SL, Samuelson CO, Williams HJ, et al. Second-line antirheumatic drugs in the elderly with rheumatoid arthritis: a post hoc analysis of three controlled trials. Pharmacotherapy 1990; 10: 79–84PubMedGoogle Scholar
  97. 97.
    Bressolle F, Bologna C, Kinowski JM, et al. Total and free methotrexate pharmacokinetics in elderly patients with rheumatoid arthritis: a comparison with young patients. J Rheumatol 1997; 24: 1903–9PubMedGoogle Scholar
  98. 98.
    Kristensen LO, Weismann K, Hutters L. Renal function and the rate of disappearance of methotrexate from serum. Eur J Clin Pharmacol 1975; 8: 439–44PubMedGoogle Scholar
  99. 99.
    Kremer JM, Petrilo GF, Hamilton RA. Pharmacokinetics and renal function in patients with rheumatoid arthritis receiving a standard dose of oral weekly methotrexate: association with significant decrease in creatinine clearance and renal clearance of the drug after 6 months of therapy. J Rheumatol 1995; 22: 38–40PubMedGoogle Scholar
  100. 100.
    Percy LA, Fang MA. Geropharmacology for the rheumatologist. Rheum Dis Clin North Am 2000; 26: 433–54PubMedGoogle Scholar
  101. 101.
    MacKinnon SK, Starkebaum G, Willkens RF. Pancytopenia associated with low-dose pulse methotrexate therapy in the treatment of rheumatoid arthritis. Semin Arthritis Rheum 1985; 15: 119–26PubMedGoogle Scholar
  102. 102.
    Wernick R, Smith DL. Central nervous system toxicity associated with weekly low-dose methotrexate therapy. Arthritis Rheum 1989; 32: 770–5PubMedGoogle Scholar
  103. 103.
    Buckley LM, Leib ES, Cartularo KS, et al. Effects of low dose methotrexate on the bone mineral density of patients with rheumatoid arthritis. J Rheumatol 1997; 24: 1489–94PubMedGoogle Scholar
  104. 104.
    Whittle SL, Hughes RA. Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. Rheumatology (Oxford) 2004; 43: 267–71Google Scholar
  105. 105.
    Morgan SL, Baggott JE, Lee JY, et al. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during long term low-dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol 1998; 25: 441–6PubMedGoogle Scholar
  106. 106.
    Jensen OK, Rasmussen C, Mollerup F, et al. Hyperhomocysteinemia in rheumatoid arthritis: influence of methotrexate treatment and folic acid supplementation. J Rheumatol 2002; 29: 1615–8PubMedGoogle Scholar
  107. 107.
    Tiftikci A, Ozdemir A, Tarcin O, et al. Influence of serum folic acid levels on plasma homocysteine concentrations in patients with rheumatoid arthritis. Rheumatol Int. In pressGoogle Scholar
  108. 108.
    Smolen JS, Kalden JR, Scott DL, et al. Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double blind randomised, multicentre trial. European Leflunomide Study Group. Lancet 1999; 353: 259–66PubMedGoogle Scholar
  109. 109.
    Maddison P, Kiely P, Kirkham B, et al. Leflunomide in rheumatoid arthritis: recommendations though a process of consensus. Rheumatology (Oxford) 2005; 44: 280–6Google Scholar
  110. 110.
    Cannon GW, Holden WL, Juhaeri J, et al. Adverse events with disease modifying antirheumatic drugs (DMARD): a cohort study of leflunomide compared with other DMARD. J Rheumatol 2004; 31: 1906–11PubMedGoogle Scholar
  111. 111.
    Van Roon EN, Jansen TL, Mourad L, et al. Leflunomide in active rheumatoid arthritis: a prospective study in daily practice. Br J Clin Pharmacol 2004; 58: 201–8PubMedGoogle Scholar
  112. 112.
    Martin K, Bentaberry F, Dumoulin C, et al. Effectiveness and safety profile of leflunomide in rheumatoid arthritis: actual practice compared with clinical trials. Clin Exp Rheumatol 2005; 23: 80–4PubMedGoogle Scholar
  113. 113.
    Kremer JM, Cannon GW. Benefit/risk of leflunomide in rheumatoid arthritis. Clin Exp Rheumatol 2004; 22Suppl. 35: 95–100Google Scholar
  114. 114.
    Pincus T, Ferraccioli GF, Sokka T, et al. Evidence from clinical trials and longterm observational studies that disease modifying anti-rheumatic drugs slow radiographic progression in rheumatoid arthritis: updating a 1983 review. Rheumatology 2002; 41: 1346–56PubMedGoogle Scholar
  115. 115.
    Jones G, Hallbert J, Crotty M, et al. The effect of treatment on radiological progression in rheumatoid arthritis: a systematic review of randomised placebo-controlled trials. Rheumatology (Oxford) 2003; 42: 6–13Google Scholar
  116. 116.
    Drosos A. Methotrexate intolerance in elderly patients with rheumatoid arthritis: what are the alternatives? Drugs Aging 2003; 20: 723–36PubMedGoogle Scholar
  117. 117.
    Kovarik JM, Koelle EU. Cyclosporin pharmacokinetics in the elderly. Drug Aging 1999; 15: 197–205Google Scholar
  118. 118.
    Gremese E, Ferraccioli GF. Benefit/risk of cyclosporine in rheumatoid arthritis. Clin Exp Rheumatol 2004; 22Suppl. 35: 101–7Google Scholar
  119. 119.
    Schiff MH, Whelton A. Renal toxicity with disease modifying antirheumatic drugs used for the treatment of rheumatoid arthritis. Semin Arthritis Rheum 2000; 30: 196–208PubMedGoogle Scholar
  120. 120.
    Suarez-Almazor ME, Belseck E, Shea B, et al. Sulfasalazine for rheumatoid arthritis. Cochrane Database Syst Rev 2000; (2): CD000958Google Scholar
  121. 121.
    Gardner G, Furst DE. Disease modifying antirheumatic drugs: potential effects in older patients. Drugs Aging 1995; 7: 420–37PubMedGoogle Scholar
  122. 122.
    Taggart AJ, McDermott BJ, Roberts SD. The effect of age and acetylator phenotype on the pharmacokinetics of sulfasalazine in patients with rheumatoid arthritis. Clin Pharmacokinet 1992; 23: 311–20PubMedGoogle Scholar
  123. 123.
    Suarez-Almazor ME, Belseck E, Shea B, et al. Antimalarials for treating rheumatoid arthritis. Cochrane Database Syst Rev 2000; (2): CD000959Google Scholar
  124. 124.
    Hurst S, Kallan MJ, Wolfe F, et al. Methotrexate, hydroxychloroquine, and intramuscular gold in rheumatoid arthritis: relative area under the curve effectiveness and sequence effects. J Rheumatol 2002; 29: 1639–45PubMedGoogle Scholar
  125. 125.
    Mavrikakis I, Sfikakis PP, Mavrikakis E, et al. The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine: a reappraisal. Ophthalmology 2003; 110: 1321–6PubMedGoogle Scholar
  126. 126.
    Rigaudiere F, Ingster-Moati I, Hache JC, et al. Up-dated ophthalmological screening and follow-up management for longterm antimalarial treatment [in French]. J Fr Ophtalmol 2004; 27: 191–9PubMedGoogle Scholar
  127. 127.
    Tozman EC, Gottlieb NL. Adverse reactions with oral and parenteral gold preparations. Med Toxicol 1987; 2: 177–89PubMedGoogle Scholar
  128. 128.
    Jones G, Brook PM. Injectable gold compounds: an overview. Br J Rheumatol 1996; 35: 1154–8PubMedGoogle Scholar
  129. 129.
    Glennas A, Kvien TK, Andrup O, et al. Auranofin is safe and superior to placebo in elderly-onset rheumatoid arthritis. Br J Rheumatol 1997; 36: 870–7PubMedGoogle Scholar
  130. 130.
    Klareskog L, van der Heijde D, de Jager JP, et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 2004; 363: 675–81PubMedGoogle Scholar
  131. 131.
    Maini RN, Breedveld FC, Kalden JR, et al. Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis Rheum 2004; 50: 1051–65PubMedGoogle Scholar
  132. 132.
    Keystone EC, Kavanaugh AF, Sharp JT, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum 2004; 50: 1400–11PubMedGoogle Scholar
  133. 133.
    Anker SD, Coats AJ. How to RECOVER from RENAISSANCE? The significance of the results of RECOVER, RENAISSANCE, RENEWAL and ATTACH. Int J Cardiol 2002; 86: 123–30PubMedGoogle Scholar
  134. 134.
    Khanna D, McMahon M, Furst DE. Anti-tumor necrosis factor α therapy and heart failure. What have we learned and where do we go from here? Arthritis Rheum 2004; 50: 1040–50PubMedGoogle Scholar
  135. 135.
    Wolfe F, Michaud K. Heart failure in rheumatoid arthritis: rates, predictors, and the effect of anti-tumor necrosis factor therapy. Am J Med 2004; 116: 305–11PubMedGoogle Scholar
  136. 136.
    Bresnihan B, Alvaro-Garcia JM, Cobby M, et al. Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum 1998; 41: 2196–204PubMedGoogle Scholar
  137. 137.
    Jiang Y, Genant HK, Watt I, et al. A multicenter, double-blind, dose ranging, randomized, placebo controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: radiologic progression and correlation of Genant and Larsen scores. Arthritis Rheum 2000; 43: 1001–9PubMedGoogle Scholar
  138. 138.
    Genovese MC, Cohen S, Moreland L, et al. Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum 2004; 50: 1412–9PubMedGoogle Scholar
  139. 139.
    Haagsma CJ, van Riel PL, de Rooij DJ, et al. Combination of methotrexate and sulphasalazine vs methotrexate alone: a randomized open clinical trial in rheumatoid arthritis patients resistant to sulphasalazine therapy. Br J Rheumatol 1994; 33: 1049–55PubMedGoogle Scholar
  140. 140.
    Dougados M, Combe B, Cantagrel A, et al. Combination therapy in early rheumatoid arthritis: a randomized, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components. Ann Rheum Dis 1999; 58: 220–5PubMedGoogle Scholar
  141. 141.
    O’Dell JR, Haire CE, Erikson N, et al. Treatment of rheumatoid arthritis with methotrexate alone, sulphasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med 1996; 334: 1287–91PubMedGoogle Scholar
  142. 142.
    Marchesoni A, Battafarano N, Arreghini M, et al. Radiographic progression in early rheumatoid arthritis: a 12-month randomized controlled study comparing the combination of cyclosporin and methotrexate with methotrexate alone. Rheumatology (Oxford) 2003; 42: 1545–9Google Scholar
  143. 143.
    Kremer JM, Genovese MC, Cannon GW, et al. Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate: a randomized, doubleblind, placebo controlled trial. Ann Intern Med 2002; 137: 726–33PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Ignazio Olivieri
    • 1
  • Carlo Palazzi
    • 1
  • Giovanni Peruz
    • 1
  • Angela Padula
    • 1
  1. 1.Rheumatology Department of LucaniaMatera and Potenza: S. Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, and the Rheumatology Division of the ‘Villa Pini’ ClinicChietiItaly

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