Skip to main content
SpringerLink
Log in

Methotrexate Intolerance in Elderly Patients with Rheumatoid Arthritis

What Are the Alternatives?

  • Therapy In Practice
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Rheumatoid arthritis (RA) in the elderly may be mild or severe, with features that are similar to those seen in younger patients. As such, the treatment regimen in the elderly is almost the same as in younger patients. Methotrexate is the most popular disease-modifying antirheumatic drug (DMARD) for the treatment of RA in the US and Europe. It has excellent efficacy and an acceptable toxicity profile. However, a number of patients do not tolerate methotrexate and an alternative DMARD should be chosen.

In the elderly, choice of an alternative DMARD should be made after careful consideration of several age-related factors including concomitant diseases, existing medication, drug compliance, and altered age-related physiology and pharmacokinetics.

In elderly patients with RA who are unable to tolerate methotrexate, the alternatives are hydroxychloroquine or sulfasalazine for mild-to-moderate disease and cyclosporin or leflunomide for severe disease, given in combination with low-dose oral corticosteroids. This is primarily due to their efficacy combined with a relatively low toxicity profile compared with other DMARDs, such as gold compounds, penicillamine, azathioprine and alkylating agents. Where the above DMARDs are contraindicated, anticytokine therapy should be considered.

The therapy of RA is a dynamic process and requires a delicate balance of benefits and risks. Experience and familiarity with the currently available agents, and knowledge of the nature of the disease are necessary in order to make better therapeutic decisions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Table IV

Similar content being viewed by others

References

  1. Harris Jr ED. Rheumatoid arthritis: pathophysiology and implications for therapy. N Engl J Med 1990 May 3; 332(18): 1277–89

    Google Scholar 

  2. Odeh M. New insights into the pathogenesis and treatment of rheumatoid arthritis. Clin Immunol Immunopathol 1997 May; 83(2): 103–16

    Article  PubMed  CAS  Google Scholar 

  3. Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001 Mar 22; 344(12): 907–16

    Article  PubMed  CAS  Google Scholar 

  4. Smyth CJ. Therapy of rheumatoid arthritis: a pyramidal plan. Postgrad Med 1972 May; 51(6): 31–9

    PubMed  CAS  Google Scholar 

  5. Scott DL, Symmons DP, Coulton BL, et al. Long-term outcome of treating rheumatoid arthritis: results after 20 years. Lancet 1987 May 16; I(8542): 1108–11

    Article  Google Scholar 

  6. Conaghan PG, Lehmann T, Brooks P. Disease-modifying antirheumatic drugs. Curr Opin Rheumatol 1997 May; 9(3): 183–90

    Article  PubMed  CAS  Google Scholar 

  7. 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 Jul 20; 333(3): 142–6

    Article  PubMed  CAS  Google Scholar 

  8. Drosos AA. Newer immunosuppressive drugs: their potential role in rheumatoid arthritis therapy. Drugs 2002; 62(6): 891–907

    Article  PubMed  CAS  Google Scholar 

  9. van Schaardenburg D, Breedveld FC. Elderly-onset rheumatoid arthritis. Semin Arthritis Rheum 1994 Jun; 23(6): 367–78

    Article  PubMed  Google Scholar 

  10. Nesher G, Moore TL, Zuckner J. Rheumatoid arthritis in the elderly. J Am Geriatr Soc 1991 Mar; 39(3): 284–94

    PubMed  CAS  Google Scholar 

  11. Nesher G, Moore TL. Rheumatoid arthritis in the aged: incidence and optimal management. Drugs Aging 1993 Nov-Dec; 3(6): 487–501

    Article  PubMed  CAS  Google Scholar 

  12. Papadopoulos IA, Katsimbri P, Alamanos Y, et al. Early rheumatoid arthritis patients: relationship of age. Rheumatol Int 2003; 23: 70–4

    PubMed  Google Scholar 

  13. Nesher G, Moore TL. Clinical presentation and treatment of arthritis in the aged. Clin Geriatr Med 1994 Nov; 10(4): 659–75

    PubMed  CAS  Google Scholar 

  14. O’Callaghan JW, Brooks PM. Disease-modifying agents and immunosuppressive drugs in the elderly. Clin Rheum Dis 1986 Apr; 12(1): 275–89

    PubMed  Google Scholar 

  15. Morgan J, Furst DE. Implications of drug therapy in the elderly. Clin Rheum Dis 1986 Apr; 12(1): 227–44

    PubMed  CAS  Google Scholar 

  16. Gardner G, Furst DE. Disease-modifying antirheumatic drugs: potential effects in older patients. Drugs Aging 1995 Dec; 7(6): 420–37

    Article  PubMed  CAS  Google Scholar 

  17. Nesher G, Moore TL. Recommendations for drug therapy of rheumatoid arthritis in elderly patients. Clin Immunother 1996; 5: 341–50

    Article  Google Scholar 

  18. Gubner R, August S, Ginsberg V. Therapeutic suppression of tissue reactivity: II. Effect of aminopterin in rheumatoid arthritis and psoriasis. Am J Med Sci 1951; 221: 176–82

    Article  PubMed  CAS  Google Scholar 

  19. Smith Jr JM, Cosulich DB, Hultquist ME, et al. The chemistry of certain pteroplutamic acid antagonists. Trans N Y Acad Sci 1948; 10: 82–3

    Article  CAS  Google Scholar 

  20. Herman RA, Veng Pedersen P, Hoffman J, et al. Pharmacokinetics of low-dose methotrexate in rheumatoid arthritis patients. J Pharm Sci 1989 Feb; 78(2): 165–71

    Article  PubMed  CAS  Google Scholar 

  21. Auvinet B, Jarrier I, Le Levier F, et al. Compared bioavailability of methotrexate administered orally or intramuscularly in rheumatoid arthritis [in French] [letter]. Presse Med 1992 May 2–9; 21(17): 822

    PubMed  CAS  Google Scholar 

  22. Oguey D, Kolliker F, Gerber NJ, et al. Effect of food on the bioavailability of low-dose methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 1992 Jun; 35(6): 611–4

    Article  PubMed  CAS  Google Scholar 

  23. Sinnett MJ, Groff GB, Raddatz DA, et al. Methotrexate pharmacokinetics in patients with rheumatoid arthritis. J Rheumatol 1989 Jun; 16(6): 745–8

    PubMed  CAS  Google Scholar 

  24. Nuernberg B, Koehnke R, Solsky M, et al. Biliary elimination of low-dose methotrexate in humans. Arthritis Rheum 1990 Jun; 33(6): 898–902

    Article  PubMed  CAS  Google Scholar 

  25. Evans ME, Ehristensen ML. Drug interactions with methotrexate. J Rheumatol 1985; 12Suppl. 12: 15–20

    CAS  Google Scholar 

  26. Cronstein BN. Molecular mechanism of methotrexate action in inflammation. Inflammation 1992 Oct; 16(5): 411–23

    Article  PubMed  CAS  Google Scholar 

  27. Kremer J. The mechanism of action of methotrexate in rheumatoid arthritis: the search continues. J Rheumatol 1994 Jan; 21(1): 1–5

    PubMed  CAS  Google Scholar 

  28. Cronstein BN. Molecular therapeutics: methotrexate and its mechanism of action. Arthritis Rheum 1996 Dec; 39(12): 1951–60

    Article  PubMed  CAS  Google Scholar 

  29. Olsen NJ, Callahan LF, Pincus T. Immunologic studies of rheumatoid arthritis patients treated with methotrexate. Arthritis Rheum 1987 May; 30(5): 481–8

    Article  PubMed  CAS  Google Scholar 

  30. Segal R, Mozes E, Yaron M, et al. The effects of methotrexate on the production and activity of interleukin-1. Arthritis Rheum 1989 Apr; 32(4): 370–7

    Article  PubMed  CAS  Google Scholar 

  31. Wilke WS, Calabrese LH, Scherbel AL. Methotrexate in the treatment of rheumatoid arthritis: pilot study. Cleve Clin Q 1980 Winter; 47(4): 305–9

    PubMed  CAS  Google Scholar 

  32. Willkens RF, Watson MA, Paxson CS. Low dose pulse methotrexate therapy in rheumatoid arthritis. J Rheumatol 1980 Jul-Aug; 7(4): 501–5

    PubMed  CAS  Google Scholar 

  33. Thompson RN, Watts C, Edelman J, et al. A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. J Rheumatol 1984 Dec; 11(6): 760–3

    PubMed  CAS  Google Scholar 

  34. Weinblatt ME, Coblyn JS, Fox DA, et al. Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med 1985 Mar 28; 312(13): 818–22

    Article  PubMed  CAS  Google Scholar 

  35. Williams HJ, Willkens RF, Samuelson Jr CO, et al. Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis: a controlled clinical trial. Arthritis Rheum 1985 Jul; 28(7): 721–30

    Article  PubMed  CAS  Google Scholar 

  36. Kremer JM, Lee JK. The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis. Arthritis Rheum 1986 Jul; 29(7): 822–31

    Article  PubMed  CAS  Google Scholar 

  37. Weinblatt ME, Trentham DE, Fraser PA. Long-term prospective trial of low-dose methotrexate in rheumatoid arthritis. Arthritis Rheum 1988 Feb; 31(2): 167–75

    Article  PubMed  CAS  Google Scholar 

  38. Drosos AA, Psychos D, Andonopoulos AP, et al. Methotrexate therapy in rheumatoid arthritis: a two year prospective follow-up. Clin Rheumatol 1990 Sep; 9(3): 333–41

    Article  PubMed  CAS  Google Scholar 

  39. Kremer JM, Phelps CT. Long-term prospective study of the use of methotrexate in the treatment of rheumatoid arthritis. Arthritis Rheum 1992; 35: 138–45

    Article  PubMed  CAS  Google Scholar 

  40. Weinblatt ME, Weissman BN, Holdsworth DE, et al. Long-term prospective study of methotrexate in the treatment of rheumatoid arthritis: 84-month update. Arthritis Rheum 1992 Feb; 35(2): 129–37

    Article  PubMed  CAS  Google Scholar 

  41. Sany J, Anaya JM, Lussiez V, et al. Treatment of rheumatoid arthritis with methotrexate: a prospective open long term study of 191 cases. J Rheumatol 1991 Sep; 18(9): 1323–7

    PubMed  CAS  Google Scholar 

  42. Hanrahan PS, Scrivens GA, Russell AS. Prospective long term follow-up of methotrexate therapy in rheumatoid arthritis: toxicity, efficacy and radiological progression. Br J Rheumatol 1989 Apr; 28(2): 147–53

    Article  PubMed  CAS  Google Scholar 

  43. Alarcon GS, Tracy IC, Blackburn Jr WD. Methotrexate in rheumatoid arthritis: toxic effects as the major factor in limiting long-term treatment. Arthritis Rheum 1989 Jun; 32(6): 671–6

    Article  PubMed  CAS  Google Scholar 

  44. Mielants H, Veys EM, Van der Straeten C, et al. The efficacy and toxicity of a constant low dose of methotrexate as a treatment for intractable rheumatoid arthritis: an open prospective study. J Rheumatol 1991 Jul; 18(7): 978–83

    PubMed  CAS  Google Scholar 

  45. Rau R, Schleusser B, Herborn G, et al. Long-term treatment of destructive rheumatoid arthritis with methotrexate. J Rheumatol 1997 Oct; 24(10): 1881–9

    PubMed  CAS  Google Scholar 

  46. Bologna C, Viu P, Picot MC, et al. Long-term follow-up of 453 rheumatoid arthritis patients treated with methotrexate: an open, retrospective, observational study. Br J Rheumatol 1997 May; 36(5): 535–40

    Article  PubMed  CAS  Google Scholar 

  47. Papadopoulos NG, Alamanos Y, Papadopoulos IA, et al. Disease modifying antirheumatic drugs in early rheumatoid arthritis: a long term observational study. J Rheumatol 2002 Feb; 29(2): 261–6

    PubMed  CAS  Google Scholar 

  48. Drosos AA, Karantanas AH, Psychos D, et al. Can treatment with methotrexate influence the radiological progression of rheumatoid arthritis? Clin Rheumatol 1990 Sep; 9(3): 342–5

    Article  PubMed  CAS  Google Scholar 

  49. Drosos AA, Tsifetaki N, Tsiakou EK, et al. Influence of methotrexate on radiographic progression in rheumatoid arthritis: a sixty-month prospective study. Clin Exp Rheumatol 1997 May-Jun; 15(3): 263–7

    PubMed  CAS  Google Scholar 

  50. Alarcon GS, Lopez-Mendez A, Walter J, et al. Radiographic evidence of disease progression in methotrexate treated and nonmethotrexate disease modifying antirheumatic drug treated rheumatoid arthritis patients: a meta-analysis. J Rheumatol 1992 Dec; 19(12): 1868–73

    PubMed  CAS  Google Scholar 

  51. Bertino J. The mechanism of action of the folate antagonists in man. Cancer Res 1963; 29: 1286–308

    Google Scholar 

  52. Rau R. Methotrexate. In: Firestein GS, Panayi GS, Wallheim FA, editors. Rheumatoid arthritis: new frontiers in pathogenesis and treatment. Oxford (UK): Oxford University Press, 2000

    Google Scholar 

  53. Kremer JM, Alarcon GS, Weinblatt ME, et al. Clinical, laboratory, radiographic, and histopathologic features of methotrexate-associated lung injury in patients with rheumatoid arthritis: a multicenter study with literature review. Arthritis Rheum 1997 Oct; 40(10): 1829–37

    Article  PubMed  CAS  Google Scholar 

  54. Weinblatt ME. Toxicity of low dose methotrexate in rheumatoid arthritis. J Rheumatol 1985 Dec; 12Suppl. 12: 35–9

    Google Scholar 

  55. Phillips C, Cera PJ, Mangan TF, et al. Clinical liver disease in patients with rheumatoid arthritis taking methotrexate. J Rheumatol 1992 Feb; 19(2): 229–33

    PubMed  CAS  Google Scholar 

  56. Seideman P, Muller-Suur R, Ekman E. Renal effects of low dose methotrexate in rheumatoid arthritis. J Rheumatol 1993 Jul; 20(7): 1126–8

    PubMed  CAS  Google Scholar 

  57. Lang B, Riegel W, Peters T, et al. Low dose methotrexate therapy for rheumatoid arthritis conplicated by pancytopenia and Pneumocystis carinii pneumonia. J Rheumatol 1991 Aug; 18(8): 1257–9

    PubMed  CAS  Google Scholar 

  58. Rustin GJ, Rustin F, Dent J, et al. No increase in second tumors after cytotoxic chemotherapy for gestational trophoblastic tumors. N Engl J Med 1983 Mar 3; 308(9): 473–6

    Article  PubMed  CAS  Google Scholar 

  59. Georgescu L, Quinn GC, Schwartzman S, et al. Lymphoma in patients with rheumatoid arthritis: association with the disease state or methotrexate treatment. Semin Arthritis Rheum 1997 Jun; 26(6): 794–804

    Article  PubMed  CAS  Google Scholar 

  60. Usman AR, Yunus MB. Non-Hodgkin’s lymphoma in patients with rheumatoid arthritis treated with low dose methotrexate. J Rheumatol 1996 Jun; 23(6): 1095–7

    PubMed  CAS  Google Scholar 

  61. Voulgari PV, Vartholomatos G, Kaiafas P, et al. Rheumatoid arthritis and B-cell chronic lymphocytic leukemia. Clin Exp Rheumatol 2002 Jan-Feb; 20(1): 63–5

    PubMed  CAS  Google Scholar 

  62. Morgan SL, Baggott JE, Vaughn WH, et al. The effect of folic acid supplementation on the toxicity of low-dose methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 1990 Jan; 33(1): 9–18

    Article  PubMed  CAS  Google Scholar 

  63. Weiblatt ME, Maier AL, Coblyn JS. Low dose leucovorin does not interfere with the efficacy of methotrexate in rheumatoid arthritis: an 8 week randomized placebo controlled trial. J Rheumatol 1993 Jun; 20(6): 950–2

    Google Scholar 

  64. Hanrahan PS, Russell AS. Concurrent use of folinic acid and methotrexate in rheumatoid arthritis. J Rheumatol 1988 Jul; 15(7): 1078–80

    PubMed  CAS  Google Scholar 

  65. Joyce DA, Will RK, Hoffmann DM, et al. Exacerbation of rheumatoid arthritis in patients treated with methotrexate after administration of folinic acid. Ann Rheum Dis 1991 Dec; 50(12): 913–4

    Article  PubMed  CAS  Google Scholar 

  66. Morgan SL, Baggott JE, Alarcon GS. Methotrexate in rheumatoid arthritis: folate supplementation should always be given. Biodrugs 1997; 8: 164–75

    Article  PubMed  CAS  Google Scholar 

  67. Kremer JM, Alarcon GS, Lightfoot Jr RW, et al. Methotrexate for rheumatoid arthritis: suggested guidelines for monitoring liver toxicity. American College of Rheumatology. Arthritis Rheum 1994 Mar; 37(3): 316–28

    Article  PubMed  CAS  Google Scholar 

  68. Clark P, Casas E, Tugwell P, et al. Hydroxychloroquine compared with placebo in rheumatoid arthritis: a randomized controlled trial. Ann Intern Med 1993 Dec 1; 119(11): 1067–71

    PubMed  CAS  Google Scholar 

  69. Esdaile JM, Suissa S, Shiroky JM, et al. A randomized trial of hydroxychloroquine in early rheumatoid arthritis: the HERA study. Am J Med 1995 Feb; 98(2): 156–68

    Article  Google Scholar 

  70. van der Heijde DM, Jacobs JW, Bijlsma JW, et al. The effectiveness of early treatment with “second-line” antirheumatic drugs: a randomized, controlled trial. Ann Intern Med 1996; 124: 699–707

    Google Scholar 

  71. American College of Rheumatology ad hoc Committee on Clinical Guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum 1996 May; 39(5): 723–31

    Article  Google Scholar 

  72. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis 2002 update. Arthritis Rheum 2002 Feb; 46(2): 328–46

    Article  CAS  Google Scholar 

  73. Pullar T, Hunter JA, Capell HA. Sulphasalazine in rheumatoid arthritis: a double blind comparison of sulphasalazine with placebo and sodium aurothiomalate. BMJ 1983 Oct 15; 287(6399): 1102–4

    Article  PubMed  CAS  Google Scholar 

  74. Williams HJ, Ward JR, Dahl SL, et al. A controlled trial comparing sulfasalazine, gold sodium thiomalate, and placebo in rheumatoid arthritis. Arthritis Rheum 1988 Jun; 31(6): 702–13

    Article  PubMed  CAS  Google Scholar 

  75. Dixon ASJ, Davies J, Dormandy TL, et al. Synthetic D(−) penicillamine in rheumatoid arthritis: double-blind controlled study of a high and low dosage regimen. Ann Rheum Dis 1975 Oct; 34(5): 416–21

    Article  PubMed  CAS  Google Scholar 

  76. Cooperative Systemic Studies of Rheumatoid Disease Group. Toxicity of long term low dose D-penicillamine therapy in rheumatoid arthritis. J Rheumatol 1987 Feb; 14(1): 67–73

    Google Scholar 

  77. Empire Rheumatism Council Research Sub-committee. Gold therapy in rheumatoid arthritis: report of a multicenter, controlled trial. Ann Rheum Dis 1960; 19: 95–119

    Article  Google Scholar 

  78. American Rheumatism Association. The Cooperative Clinics Committee. A controlled trial of gold salt therapy in rheumatoid arthritis. Arthritis Rheum 1973 May-Jun; 16(3): 353–8

    Article  Google Scholar 

  79. Sigler JW, Bluhim GB, Duncan H, et al. Gold salts in the treatment of rheumatoid arthritis: a double blind study. Ann Intern Med 1974; 80: 21–6

    PubMed  CAS  Google Scholar 

  80. Sambrook PN, Browne CD, Champion GD, et al. Terminations of treatment with gold sodium thiomalate in rheumatoid arthritis. J Rheumatol 1982 Nov-Dec; 9(6): 932–4

    PubMed  CAS  Google Scholar 

  81. Ward JR, Williams HJ, Egger MJ, et al. Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis: a controlled clinical trial. Arthritis Rheum 1983 Nov; 26(11): 1303–15

    Article  PubMed  CAS  Google Scholar 

  82. Urowitz MB, Gordon DA, Smythe HA, et al. Azathioprine in rheumatoid arthritis: a double-blind crossover study. Arthritis Rheum 1973 May-Jun; 16(3): 411–8

    Article  PubMed  CAS  Google Scholar 

  83. Woodland S, Chaput de Saintouge DM, Evans SJ, et al. Azathioprine in rheumatoid arthritis: a double blind study of full versus half doses versus placebo. Ann Rheum Dis 1981; 40: 355–9

    Article  PubMed  CAS  Google Scholar 

  84. Yocum DE, Torley H. Cyclosporin in rheumatoid arthritis. Rheum Dis Clin North Am 1995 Aug; 21(3): 835–44

    PubMed  CAS  Google Scholar 

  85. Landewe RB, Goei The HS, van Rijthoven AW, et al. A randomized, double blind, 24-week controlled study of low-dose cyclosporin versus chloroquine for early rheumatoid arthritis. Arthritis Rheum 1994 May; 37(5): 637–43

    Article  PubMed  CAS  Google Scholar 

  86. Forre O, Norwegian Arthritis Study Group. Radiologic evidence of disease modification in rheumatoid arthritis patients treated with cyclosporin: results of a 48-week multicenter study comparing low-dose cyclosporin with placebo. Arthritis Rheum 1994 Oct; 37(10): 1506–12

    Article  PubMed  CAS  Google Scholar 

  87. Pasero G, Priolo F, Marubini E, et al. Slow progression of joint damage in early rheumatoid arthritis treated with cyclosporin A. Arthitis Rheum 1996 Jun; 39(6): 1006–15

    Article  CAS  Google Scholar 

  88. Drosos AA, Voulgari PV, Papadopoulos IA, et al. Cyclosporin A in the treatment of early rheumatoid arthritis: a prospective randomized 24-month study. Clin Exp Rheumatol 1998 Nov-Dec; 16(6): 695–701

    PubMed  CAS  Google Scholar 

  89. Drosos AA, Voulgari PV, Katsaraki A, et al. Influence of cyclosporin A on radiological progression in early rheumatoid arthritis patients: a 42-month prospective study. Rheumatol Int 2000; 19(3): 113–8

    Article  PubMed  CAS  Google Scholar 

  90. Kovarik JM, Koelle EU. Cyclosporin pharmacokinetics in the elderly. Drugs Aging 1999 Sep; 15(3): 197–205

    Article  PubMed  CAS  Google Scholar 

  91. Landewe RB, Goei The HS, van Rijthoven AW, et al. Cyclosporin in common clinical practice: an estimation of the benefit/risk ratio in patients with rheumatoid arthritis. J Rheumatol 1994 Sep; 21(9): 1631–6

    PubMed  CAS  Google Scholar 

  92. Torley H, Yocum D. Effects of dose treatment duration on adverse experience with cyclosporin in RA: analysis of North American Trials [abstract 1041]. Arthritis Rheum 1994; 37Suppl. S334: 334

    Google Scholar 

  93. Cash JM, Wilder RL. Refractory rheumatoid arthritis: therapeutic options. Rheum Dis Clin North Am 1995 Feb; 21(1): 1–18

    PubMed  CAS  Google Scholar 

  94. Caldwell JR, Furst DE. The efficacy and safety of low-dose corticosteroids for rheumatoid arthritis. Semin Arthritis Rheum 1991 Aug; 21(1): 1–11

    Article  PubMed  CAS  Google Scholar 

  95. van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, et al. 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 Jan 1; 136(1): 1–12

    PubMed  Google Scholar 

  96. Lockie LM, Gomez E, Smith DM. Low dose adrenocorticosteroids in the management of elderly patients with rheumatoid arthritis: selected examples and summary of efficacy in the long-term management of 97 patients. Semin Arthritis Rheum 1983 May; 12(4): 373–81

    Article  PubMed  CAS  Google Scholar 

  97. van Schaardenburg D, Valkema R, Dijkmans BA, et al. Prednisone treated of elderly-onset rheumatoid arthritis: disease activity and bone mass in comparison with chloroquine threatment. Arthritis Rheum 1995 Mar; 38(3): 334–42

    Article  PubMed  Google Scholar 

  98. Buckley LM, Leib ES, Cartularo KS, et al. Effects of low dose corticosteroids on the bone mineral density of patients with rheumatoid arthritis. J Rheumatol 1995 Jun; 22(6): 1055–9

    PubMed  CAS  Google Scholar 

  99. American College of Rheumatology Task Force on Osteoporosis Guidelines. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum 1996 Nov; 39(11): 1791–801

    Article  Google Scholar 

  100. Smith MD, Bertouch JV, Smith AM, et al. The clinical and immunological effects of pulse methylprednisolone therapy in rheumatoid arthritis: I. Clinical effects. J Rheumatol 1988 Feb; 15(2): 229–32

    PubMed  CAS  Google Scholar 

  101. Mladenovic V, Domljan Z, Rozman B, et al. Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis: results of a randomized, placebo-controlled, phase II study. Arthritis Rheum 1995 Nov; 38(11): 1595–603

    Article  PubMed  CAS  Google Scholar 

  102. Strand V, Tugwell P, Bombardier C, et al. Function and health-related quality of life: results from a randomized controlled trial of leflunomide versus methotrexate or placebo in patients with active rheumatoid arthritis. Leflunomide Rheumatoid Arthritis Investigators Group. Arthritis Rheum 1999 Sep; 42(9): 1870–8

    Article  PubMed  CAS  Google Scholar 

  103. Tugwell P, Wells G, Strand V, et al. Clinical improvement as reflected in measures of function and health-related quality of life following treatment with leflunomide compared with methotrexate in patients with rheumatoid arthritis: sensitivity and relative efficiency to detect a treatment effect in a twelvemonth, placebo-controlled trial. Leflunomide Rheumatoid Arthritis Investigators Group. Arthritis Rheum 2000 Mar; 43(3): 506–14

    Article  PubMed  CAS  Google Scholar 

  104. Schiff MH, Goldmlum R, Rees MMC. New DMARD, mycophenolate mofetil, effectively treats refractory rheumatoid arthritis patients for one year [abstract]. Arthritis Rheum 1991; 34: S157

    Google Scholar 

  105. Maini RN, Breedveld FC, Kalden JR, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998 Sep; 41(9): 1552–63

    Article  PubMed  CAS  Google Scholar 

  106. Maini R, St Clair EW, Breedveld F, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomized phase III trial. ATTRACT Study Group. Lancet 1999 Dec 4; 354(9194): 1932–9

    Article  PubMed  CAS  Google Scholar 

  107. Lipsky PE, van der Heijde DM, St Clair EW, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis: antitumor necrosis factor trial in rheumatoid arthritis with Concomitant Therapy Study Group. N Engl J Med 2000 Nov 30; 343(22): 1594–602

    Article  PubMed  CAS  Google Scholar 

  108. Temekonidis TI, Georgiadis AN, Alamanos Y, et al. Infliximab treatment in combination with cyclosporin A in patients with severe refractory rheumatoid arthritis. Ann Rheum Dis 2002 Sep; 61(9): 822–5

    Article  PubMed  CAS  Google Scholar 

  109. Weinblatt ME, Kremer JM, Bankhurst AD. A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999 Jan 28; 340(4): 253–9

    Article  PubMed  CAS  Google Scholar 

  110. Moreland LW, Baumgartner SW, Schiff MH, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997 Jul 17; 337(3): 141–7

    Article  PubMed  CAS  Google Scholar 

  111. Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000 Nov 30; 343(22): 1586–93

    Article  PubMed  CAS  Google Scholar 

  112. Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001 Oct 11; 345(15): 1098–104

    Article  PubMed  CAS  Google Scholar 

  113. Liberopoulos EN, Drosos AA, Elisaf MS. Exacerbation of tuberculosis enteritis after treatment with infliximab [letter]. Am J Med 2002 Nov; 113(7): 615

    Article  PubMed  Google Scholar 

  114. Jobanputra P, Maggs F, Homer D, et al. Monitoring and assessing the safety of disease modifying antirheumatic drugs: a west Midland experience. Drug Saf 2002; 25: 1099–106

    Article  PubMed  CAS  Google Scholar 

  115. Bresnihan B, Alvaro-Gracia JM, Cobby M, et al. Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum 1998 Dec; 41(12): 2196–204

    Article  PubMed  CAS  Google Scholar 

  116. 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 May; 43(5): 1001–9

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The author would like to thank Mrs Eleni Horti for her secretarial assistance. No sources of funding were used to assist in the preparation of this manuscript. The author has no conflicts of interest that are directly relevant to the content of this manuscript.

Author information

Authors and Affiliations

  1. Section of Rheumatology, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, 45 110, Greece

    Alexandros A. Drosos

Authors
  1. Alexandros A. Drosos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexandros A. Drosos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Drosos, A.A. Methotrexate Intolerance in Elderly Patients with Rheumatoid Arthritis. Drugs Aging 20, 723–736 (2003). https://doi.org/10.2165/00002512-200320100-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-200320100-00002

Keywords

Search

Navigation