Skip to main content
SpringerLink
Log in

Efficacy, Tolerability and Cost Effectiveness of Disease-Modifying Antirheumatic Drugs and Biologic Agents in Rheumatoid Arthritis

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Over the last decade, several new drugs have become available for the treatment of patients with rheumatoid arthritis. These agents include the new disease-modifying antirheumatic drug (DMARD) leflunomide and the biologic agents, tumor necrosis factor (TNF)-α antagonists and an interleukin (IL)-1 receptor antagonist.

Methotrexate is commonly used as the first DMARD, has a well documented clinical efficacy and slows radiological deterioration. Sulfasalazine appears to have similar properties, albeit to a lesser extent. Leflunomide has similar efficacy as methotrexate but it is less tolerated than sulfasalazine. The adverse effect profiles of these three drugs makes regular laboratory monitoring mandatory.

Several combination therapies with DMARDs were proven to be more effective than mono-DMARD therapy. However, until now these strategies have not been widely adopted.

TNF antagonists are potent anti-inflammatory drugs, with a rapid onset of effects compared with traditional DMARDs. The IL-1 receptor antagonist, anakinra, has an intermediate place between methotrexate and the TNF antagonists with respect to efficacy.

The adverse effects of TNF antagonists include an increased incidence of common and opportunistic infections. Thus far, anakinra has not been associated with an enhanced rate of opportunistic infections.

Some of the biologic agents have been associated with worsening heart failure and demyelinating disease. The limited long-term safety data of the biologic agents are a point of concern because, at present, an enhanced risk for malignancies, particularly lymphoma, can not be excluded.

Drug costs of traditional DMARDs are up to $US3000 per year, whereas for the biologics the yearly drug costs range between $US16 000 and >$US20 000. Cost-effectiveness analyses are necessary to determine whether or not these high costs are justified. Unfortunately, adequate, prospective, economic evaluations are not yet available. Until these become available, treatment decisions will be based on the balance of direct costs and indirect costs and expected cost savings in the future.

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
Table V
Table VI
Table VII

Similar content being viewed by others

References

  1. Lems WF, Dijkmans BAC. Rheumatoid arthritis: clinical aspects and its variants. In: Firestein GS, Panayi GS, Wollheim FA, editors. Rheumatoid arthritis: new frontiers in pathogenesis and treatment. New York: Oxford University Press 2000: 213–25

    Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Yelin E, Wanke LA. An assessment of the annual and long-term direct costs of rheumatoid arthritis: the impact of poor function and functional decline. Arthritis Rheum 1999; 42: 1209–18

    Article  PubMed  CAS  Google Scholar 

  4. Cooper NJ. Economic burden of rheumatoid arthritis: a systematic review. Rheumatology (Oxford) 2000; 39: 28–33

    Article  CAS  Google Scholar 

  5. American College of Rheumatology ad hoc Committees on Clinical Guidelines. Guidelines for the management of rheumatoid arthritis. Arthritis Rheum 1996; 39: 713–22

    Article  Google Scholar 

  6. Fries JF. Current treatment paradigms in rheumatoid arthritis. Rheumatology 2000; 39 Suppl. 1: 30–5

    Article  PubMed  Google Scholar 

  7. Rau R. Methotrexate. In: Firestein GS, Panayi GS, Wollheim FA, editors. Rheumatoid arthritis: new frontiers in pathogenesis and treatment. Oxford (NY): Oxford University Press, 2000: 337–50

    Google Scholar 

  8. Aletahaq D, Stamm T, Kapral T, et al. Survival and effectiveness of leflunomide compared with methotrexate and sulfasalazine in rheumatoid arthritis: a matched observational study. Ann Rheum Dis 2003; 62: 944–51

    Article  Google Scholar 

  9. Capell H, Madhok R. Disease-modifying antirheumatic drugs, 2: sulfasalazine and dapson. In: Huchberg MC, Silman AD, Smollen JS, et al., editors. Rheumatoloy. Edinburgh: Mosby, 2003: 405–16

    Google Scholar 

  10. Boers M. Rheumatoid arthritis: treatment of early disease. Rheum Dis Clin North Am 2001; 27: 405–14

    Article  PubMed  CAS  Google Scholar 

  11. Cush JJ. Cytokine therapies. In: Huchberg MC, Silman AD, Smollen JS, et al., editors. Rheumatoloy. Edinburgh: Mosby, 2003: 405–16

    Google Scholar 

  12. Nurmohamed MT, van Halm V, Dijkmans BAC. Cardiovascular risk profile of antirheumatic agents in patients with osteoar-thritis and rheumatoid arthritis. Drugs 2002; 62(11): 1599–609

    Article  PubMed  CAS  Google Scholar 

  13. Kirwan JR. Systemic low-dose glucocorticoid in rheumatoid arthritis. Rheum Dis Clin North Am 2001; 27: 389–403

    Article  PubMed  CAS  Google Scholar 

  14. Telia MN, Feinglass J, Chang RW. Cost-effectiveness, cost-utility, and cost-benefit studies in rheumatology: a review of the literature, 2001–2002. Curr Opin Rheumatol 2003; 15: 127–31

    Article  Google Scholar 

  15. Bakker CH, Rutten-van Molken MPMH, van Doorslaar EK, et al. Health related utility assessment by rating scale and standard gamble in patients with ankylosing spondylitis or fibromyalgia. Patient Educ Couns 1993; 20: 145–52

    Article  PubMed  CAS  Google Scholar 

  16. Cronstein BN, Eberle MA, Gruber HE, et al. Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells. Proc Natl Acad Sci U S A 1991; 88: 2441–5

    Article  PubMed  CAS  Google Scholar 

  17. Cronstein BN, Naime D, Ostad E. The antiinflammatory mechanism of methotrexate: increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 1993; 92: 2675–82

    Article  PubMed  CAS  Google Scholar 

  18. Hamilton RA, Kremer JM. Why intramuscular methotrexate may be more efficacious than oral dosing in patients with rheumatoid arthritis. Br J Rheumatol 1997; 36: 86–90

    Article  PubMed  CAS  Google Scholar 

  19. van Ede AE, Laan RFJM, Rood MJ, et al. Effect of folic or folinic acid supplementation on toxicity and efficacy of methotrexate in rheumatoid arthritis: a double blind randomised placebo-controlled multi-centre 48-week study. Arthritis Rheum 2001; 44: 1515–24

    Article  PubMed  Google Scholar 

  20. Willkens RF, Watson MA, Paxson CS. Low-dose pulse methotrexate in rheumatoid arthritis. J Rheumatol 1980; 7: 501–5

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  22. Hoffmeister RT. Methotrexate therapy in rheumatoid arthritis: 15 years experience. Am J Med 1983; 75: 69–73

    Article  PubMed  CAS  Google Scholar 

  23. Anderson PA, Wets SG, O’Dell JR, et al. Weekly pulse methotrexate in rheumatoid arthritis. Ann Intern Med 1985; 103: 489–96

    Google Scholar 

  24. Thompson RN, Watts C, Edelman J, et al. A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. J Rheumatol 1984; 11: 760–2

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  26. Williams HJ, Willkens RF, Samuelson 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; 28: 721–9

    Article  PubMed  CAS  Google Scholar 

  27. Tugwell P, Bennett K, Gent M. Methotrexate in rheumatoid arthritis. Ann Intern Med 1987; 107: 358–66

    PubMed  CAS  Google Scholar 

  28. Pincus T, Marcum SB, Callahan LF. Long-term drug therapy for rheumatoid arthritis in seven rheumatology private practices: II. Second line drugs and prednisone. J Rheumatol 1992; 19: 1885–94

    CAS  Google Scholar 

  29. Boers M, Verhoeven AC, Markusse HM, et al. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 1997; 350: 309–18

    Article  PubMed  CAS  Google Scholar 

  30. O’Dell JR, Haire CE, Erikson N, et al. Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydrox-ychloroquine, or a combination of all three medications. N Engl J Med 1996; 334: 1287–91

    Article  PubMed  Google Scholar 

  31. Haagsma U, van Riel PLCM, De Jong AJL, et al. Combination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: a randomised, controlled, double-blind, 52 week clinical trial. Br J Rheumatol 1997; 36: 1082–8

    Article  PubMed  CAS  Google Scholar 

  32. Karger T, Rau R. Treatment of chronic polyarthritis with low-dose methotrexate [in German]. Dtsch Med Wochenschr 1988 May 27; 113(21): 839–46

    Article  PubMed  CAS  Google Scholar 

  33. Mottonen T, Hannonen P, Leirisalo-Repo M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. Lancet 1999; 353: 1568–73

    Article  PubMed  CAS  Google Scholar 

  34. 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 

  35. Buchbinder R, Hall S, Sambrook PN, et al. Methotrexate therapy in rheumatoid arthritis: a life table review of 587 patients treated in community practice. J Rheumatol 1993; 20: 639–44

    PubMed  CAS  Google Scholar 

  36. Weinblatt ME, Trentham DE, Fraser PA. Longterm prospective trial of low-dose methotrexate in rheumatoid arthritis. Arthritis Rheum 1988; 31: 167–75

    Article  PubMed  CAS  Google Scholar 

  37. 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; 32: 671–6

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  39. Kremer JM, Lee JK. A long-term prospective study of the use of I: methotrexate in rheumatoid arthritis: update after a mean of fifty-three months. Arthritis Rheum 1988; 31: 477–584

    Google Scholar 

  40. Gutierrez-Urena S, Molina JF, Garcia CO, et al. Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis. Arthritis Rheum 1996; 39: 272–6

    Article  PubMed  CAS  Google Scholar 

  41. Thomas MH, Gutterman LA. Methotrexate toxicity in a patient receiving trimethoprim-sulfamethoxazole. J Rheumatol 1986; 13: 440–1

    PubMed  CAS  Google Scholar 

  42. Tanaka Y, Shiozawa K, Nishibayashi Y, et al. Methotrexate induced early onset pancytopenia in rheumatoid arthritis: drug allergy? Idiosyncrasy? J Rheumatol 1992; 19: 1320–1

    PubMed  CAS  Google Scholar 

  43. Cannon GW. Methotrexate pulmonary toxicity. Rheum Dis Clin North Am 1997; 23: 917

    Article  PubMed  CAS  Google Scholar 

  44. Carson CW, Cannon GW, Egger MJ, et al. Pulmonary disease during the treatment of rheumatoid arthritis with low-dose pulse methotrexate. Semin Arthritis Rheum 1987; 16: 186–95

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  46. Phillips C, Cera PJ, Mangan TF, et al. Clinical liver disease in rheumatoid arthritis patients on methotrexate. J Rheumatol 1992; 19: 229–33

    PubMed  CAS  Google Scholar 

  47. Rau R. Toxicity of methotrexate in rheumatoid arthritis. In: Weinblatt ME, editor. A comprehensive guide to new therapeutic approaches of methotrexate in rheumatoid arthritis. Chicago (IL): Pharma Libri, 1987: 63–77

    Google Scholar 

  48. Kremer JM, Alarcón GS, Lightfoot Jr RW, et al. Methotrexate for rheumatoid arthritis: suggested guidelines for monitoring liver toxicity. Arthritis Rheum 1994; 37: 316–28

    Article  PubMed  CAS  Google Scholar 

  49. Scideman P, Muller-Suur R, Ekman E. Renal effects of low dose methotrexate in rheumatoid arthritis. J Rheumatol 1993; 20: 1126–8

    Google Scholar 

  50. Kremer JM, Petrillo GF, Hamilton RA. Pharmacokinetics and renal function in patients with rheumatoid arthritis receiving a standard dose of oral weekly methotrexate: association with significant decreases in creatinine clearance and renal clearance of the drug after 6 months of therapy. J Rheumatol 1995; 22: 38–40

    PubMed  CAS  Google Scholar 

  51. Buckley LM, Bullaboy CA, Leichtman L, et al. Multiple congenital anomalies associated with weekly low-dose methotrexate treatment of the mother. Arthritis Rheum 1997; 40: 971–3

    Article  PubMed  CAS  Google Scholar 

  52. Beauparlant P, Papp K, Haraoui B. The incidence of cancer associated with the treatment of rheumatoid arthritis. Semin Arthritis Rheum 1999; 29: 148–58

    Article  PubMed  CAS  Google Scholar 

  53. Starkebaum G. Rheumatoid arthritis, methotrexate, and lymphama: risk substitution, or cat and mouse with Epstein-Barr virus. J Rheumatol 2001; 28: 2573–5

    PubMed  CAS  Google Scholar 

  54. Mariette X, Cazals-Hatem D, Warszawki J, et al. Lymphoma’s in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France. Blood 2002; 99: 3909–15

    Article  PubMed  CAS  Google Scholar 

  55. 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; 26: 794–04

    Article  PubMed  CAS  Google Scholar 

  56. Salloum E, Cooper DL, Howe G, et al. Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases. J Clin Oncol 1996; 14: 1943–9

    PubMed  CAS  Google Scholar 

  57. Moder KG, Tefferi A, Cohen MD, et al. Hematologic malignancies and the use of methotrexate in rheumatoid arthritis: a retrospective study. Am J Med 1995; 99: 276–81

    Article  PubMed  CAS  Google Scholar 

  58. Rains CP, Noble S, Faulds D. Sulfasalazine: a review of its pharmacological properties and therapeutic efficacy in treatment of rheumatoid arthritis. Drugs 1995; 50: 137–56

    Article  PubMed  CAS  Google Scholar 

  59. Schroder H, Campbell D. Absorption, metabolism and excretion of salicylazo-sulfapyridine in man. Clin Pharmacol Ther 1972; 13: 539–51

    PubMed  CAS  Google Scholar 

  60. Pullar T, Hunter JA, Capell HA. Which component of sulphasalazine is active in rheumatoid arthritis. BMJ 1985; 290: 1535–8

    Article  PubMed  CAS  Google Scholar 

  61. Porter DR, Capell HA. The use of sulfasalzine as a disease modifyinig antirheumatic drug. Baillieres Clin Rheumatol 1990; 4: 535–51

    Article  PubMed  CAS  Google Scholar 

  62. Bird HA. Sulphasalzine, sulfapyridine or 5-aminosalicylic acid-which is the active moiety in rheumatoid arthitis. Br J Rheumatol 1995; 35 Suppl. 2: 16–9

    Google Scholar 

  63. Pullar T, Hunter JA, Capell HA. Effect of sulphasalazine on the radiological progression of rheumatoid arthritis. Ann Rheum Dis 1987; 46: 398–402

    Article  PubMed  CAS  Google Scholar 

  64. Van der Heijde DM, van Riel PLCM, Nuver-Zwart IH, et al. Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis. Lancet 1989; I: 1036–8

    Article  Google Scholar 

  65. Van der Heijde DM, van Riel PLCM, Nuver-Zwart IH, et al. Alternative methods for analysis of radiographic damage in a randomized, double-blind, parallel group clinical trial comparing hydroxychloroquine and sulfasalazine. J Rheumatol 2000; 27: 535–8

    PubMed  Google Scholar 

  66. Wolfe F, Cush JJ, O’Dell JR, et al. Consensus recommendations for the assessment and treatment of rheumatoid arthritis. J Rheumatol 2001 Jun; 28(6): 1423–30

    PubMed  CAS  Google Scholar 

  67. Maetzel A, Wond A, Strand V, et al. Meta-analysis of treatment termination rates among rheumatoid arthritis patients receiving disease-modifying anti-rheumatic drugs. Rheumatology 2000; 39: 975–81

    Article  PubMed  CAS  Google Scholar 

  68. Amos R, Pullar T, Bax DE, et al. Sulphasalazine for rheumatoid arthritis: toxicity in 774 patients monitored for one to 11 years. BMJ (Clin Res Ed) 1986; 293: 420–3

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  70. Donvan S, Hawley S, MacCarthy J, et al. Tolerability of enteric-coated sulphasalazine in rheumatoid arthritis: results of a cooperating clinics study. Br J Rheumatol 1990; 29: 201–4

    Article  Google Scholar 

  71. Nurmohamed MT, Soesan M, van Oers MHJ, et al. Cyclosporin for sulfasalazine-induced aplastic anaemia in a patient with rheumatoid arthritis. Rheumatology 2000; 39: 1431–3

    Article  PubMed  CAS  Google Scholar 

  72. Mogadam M, Dobbins 3rd WO, Korelitz BI, et al. Pregnancy in inflammatory bowel disease: effect of sulfasalazine and corti-costeroids on fetal outcome. Gastroenterology 1981 Jan; 80(1): 72–6

    PubMed  CAS  Google Scholar 

  73. Xu X, Williams JW, Gong H, et al. Two activities of the immunosuppressive metabolite of leflunomide, A77-1726: inhibition of pyrimidine nucleotide synthesis and protein tyro-sine phosphorylation. Biochem Pharmacol 1996; 52: 527–34

    Article  PubMed  CAS  Google Scholar 

  74. Elder RT, Xu X, Williams JW, et al. The immunosuppressive metabolite of leflunomide, A77 1726, affects murine T cells through two biochemical mechanisms. J Immunol 1997; 159: 22–7

    PubMed  CAS  Google Scholar 

  75. Ruckemann K, Fairbanks LD, Carrey EA, et al. A. Leflunomide inhibits pyrimidine de novo synthesis in mitogen-stimulated T-lymphocytes from healthy humans. J Biol Chem 1998; 273: 21682–91

    CAS  Google Scholar 

  76. Mattar T, Kochhar K, Bartlett R, et al. Inhibition of the epidermal growth factor receptor tyrosine kinase activity by leflunomide. FEBS Lett 1993; 334: 161–4

    Article  PubMed  CAS  Google Scholar 

  77. Xu XL, Williams JW, Bremer EG, et al. Inhibition of protein tyrosine phosphorylation in T cells by a novel immunosuppressive agent, leflunomide. J Biol Chem 1995; 270: 12398–403

    Article  PubMed  CAS  Google Scholar 

  78. Siemasko K, Chong AS, Jack HM, et al. Inhibition of JAK3 and STAT6 tyrosine phosphorylation by the immunosuppressive drug leflunomide leads to a block in IgG1 production. J Immunol 1998; 160: 1581–8

    PubMed  CAS  Google Scholar 

  79. Manna SK, Aggarwal BB. Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-κB activation and gene expression. J Immunol 1999; 162: 2095–102

    PubMed  CAS  Google Scholar 

  80. Kraan MC, Reece RJ, Barg EC, et al. Modulation of inflammation and metalloproteinase expression in synovial tissue by leflunomide and methotrexate in patients with active rheumatoid arthritis: findings in a prospective, randomized, double-blind, parallel-design clinical trial in thirty-nine patients at two centers. Arthritis Rheum 2000; 43: 1820–30

    Article  PubMed  CAS  Google Scholar 

  81. Kraan MC, de Koster BM, Elferink JG, et al. Inhibition of neutrophil migration soon after initiation of treatment with leflunomide or methotrexate in patients with rheumatoid arthritis: findings in a prospective, randomized, double-blind clinical trial in fifteen patients. Arthritis Rheum 2000; 43: 1488–95

    Article  PubMed  CAS  Google Scholar 

  82. Schrand LM, Tuetken R. Rheumatoid arthritis: update on the newest DMARDs and their potential place in therapy. Formulary 2002 Jun 1;37: 301–11

    CAS  Google Scholar 

  83. Osiri M, Shea B, Suarez Almazor M, et al. Leflunomide for the treatment of rheumatoid arthritis: a systematic review and metaanalysis. J Rheumatol 2003; 30: 1182–90

    PubMed  CAS  Google Scholar 

  84. Mladenovic V, Domljan Z, Rozman B, et al. Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Arthritis Rheum 1995; 38: 1595–603

    Article  PubMed  CAS  Google Scholar 

  85. Strand V, Cohen S, Schiff M, et al. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Arch Intern Med 1999; 159: 2542–50

    Article  PubMed  CAS  Google Scholar 

  86. 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. Lancet 1999; 353: 259–66

    Article  PubMed  CAS  Google Scholar 

  87. Emery P, Breedveld FC, Lemmel EM, et al. A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatology 2000; 39: 655–65

    Article  PubMed  CAS  Google Scholar 

  88. Cohen S, Cannon GW, Schiff M, et al. Two-year, blinded, randomized, controlled trial of treatment of rheumatoid arthritis with leflunomide compared with methotrexate. Arthritis Rheum 2001; 44: 1984–92

    Article  PubMed  CAS  Google Scholar 

  89. Scott DL, Smolen JS, Kalden JR, et al. Treatment of active rheumatoid arthritis with leflunomide: two year follow-up of a double blind placebo controlled trial versus sulfasalazine. Ann Rheum Dis 2001; 60: 913–23

    Article  PubMed  CAS  Google Scholar 

  90. Weinblatt MW, Kremer JM, Coblyn JS, et al. Pharmacokinetics, safety and efficacy of combination treatmetn with methotrexate and leflunomide in patients with active rheumatoid arthritis. Arthritis Rheum 1999; 42: 1322–8

    Article  PubMed  CAS  Google Scholar 

  91. Kremer JM, Genovese MC, Cannon GW, et al. Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. Ann Intern Med 2002; 137: 726–33

    PubMed  CAS  Google Scholar 

  92. Hewitson PJ, Debroe S, McBride A, et al. Leflunomide and rheumatoid arthritis: a systematic review of effectiveness, safety and cost implications. J Clin Pharm Ther 2000; 25: 295–302

    Article  PubMed  CAS  Google Scholar 

  93. Felson DT, Anderson JJ, Boers M, et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995; 38: 727–35

    CAS  Google Scholar 

  94. van Riel PL, Smolen JS, Emery P, et al. Leflunomide: a manageable safety profile. J Rheumatol Suppl 2004 Jun; 71: 21–4

    PubMed  Google Scholar 

  95. Smolen JS, Emery P. Efficacy and safety of leflunomide in active rheumatoid arthritis. Rheumatology 2000; 39 Suppl. 1: 48–56

    Article  PubMed  CAS  Google Scholar 

  96. Van Pelt A, van Schaardenburg DJ, Bultink IEM, et al. High discontinuation rate of treatment with leflunomide in daily practice [abstract]. Arthritis Rheum 2001; 44 Suppl.: S143

    Google Scholar 

  97. Van Halm VP, Nurmohamed MT, van Schaardenburg D, et al. Leflunomide does not alter the lipid profile in rheumatoid arthritis [abstract]. Ann Rheum Dis 2003; 62 Suppl. 1: 155

    Google Scholar 

  98. Prokopowitsch AS, Diogenes AHM, Borgees CT, et al. Leflunomide induces progressive increase in rheumatoid arthritis lipid profile [abstract]. Arthritis Rheum 2002; 46 Suppl.: S164

    Google Scholar 

  99. European Agency for the evaluation of Medicinal Products [online]. Available from URL: http://www.emea.eu.int/pdfs/human/press/pus/561101en.pdf [Accessed 2003 Sep 13]

  100. Food and Drug Administration [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/03/briefing/3930b2.htm [Accessed 2003 Sep 13]

  101. Hoechst Marion Roussel. Arava™ (leflunomide) prescribing information. Kansas City (MO): Hoechst Marion Roussel 1998

    Google Scholar 

  102. Arava prescribing information [online]. Available from URL: http://www.aventispharma-us.com/PIs/arava_TXT.html [Accessed 2003 Oct 19]

  103. Lee DL, Weinblatt ME. Rheumatoid arthritis. Lancet 2001; 358: 903–11

    Article  PubMed  CAS  Google Scholar 

  104. Elliott M, Maini R, Feldmann M, et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factorα. Lancet 1994; 344: 1125–7

    Article  PubMed  CAS  Google Scholar 

  105. Markham A, Lamb HM. Infliximab: a review of its use in the management of rheumatoid arthritis. Drugs 2000; 59: 1341–59

    Article  PubMed  CAS  Google Scholar 

  106. Elliott MJ, Maini RN, Feldmann M, et al. Randomized double-blind comparison of chimeric monoclonal antibody to tumor necrosis factora (cA2) versus placebo in rheumatoid arthritis. Lancet 1994; 344: 1105–10

    Article  PubMed  CAS  Google Scholar 

  107. Maini RN, Breedveld FC, Kalden JR, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factora monoclonal antibody combined with low dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1999; 41: 1552–63

    Article  Google Scholar 

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

    CAS  Google Scholar 

  109. Smolen JS, Emery P, Bathon J, et al. Treatment of early rheumatoid arthritis with infliximab plus methotrexate or methotrexate alone: preliminary results of the ASPIRE trial [abstract]. Ann Rheum Dis 2003; 62 Suppl. 1: 64

    Article  Google Scholar 

  110. The European Agency for the Evaluation of Medicinal Products. European Public Assessment Report (EPAR): remicade — all summary of product characteristics [online]. Available from URL: http://www.emea.eu.int/humandocs/Humans/EPAR/Remicade/Remicade.htm [Accessed 2005 Feb 1]

  111. Hyrich KL, Silman AJ, Watson KD, et al. Anti-tumour necrosis factor alpha therapy in rheumatoid arthritis: an update on safety. Ann Rheum Dis 2004 Dec; 63(12): 1538–43

    Article  PubMed  CAS  Google Scholar 

  112. Neven N, Vis M, Voskuyl AE, et al. Safety of infliximab in daily practice in patients with rheumatoid arthritis [abstract]. Ann Rheum Dis 2003; 62 Suppl. 1: 175

    Google Scholar 

  113. Strand V, Keystone E. Anticytokine therapies in rheumatoid arthritis. In: Rose BD, editor. UpToDate. Wellesley (MA): UpToDate, 2003

    Google Scholar 

  114. Francis GS. TNF-α and heart failure: the difference between proof of principle and hypothesis testing. Circulation 1999; 99: 3213–4

    Article  PubMed  CAS  Google Scholar 

  115. Chung ES, Packer M, Hung Lo K, et al. Randomized, double-blind placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-α, in patients with moderate-to-severe heart failure: results of the anti-TNF therapy against congestive heart failure. Circulation 2003; 107: 3133–40

    Article  PubMed  CAS  Google Scholar 

  116. Kwon HJ, Cote TR, Cuffe MS, et al. Case reports of heart failure after therapy with a tumor necrosis factor antagonist. Ann Intern Med 2003; 138(10): 807–11

    PubMed  Google Scholar 

  117. Food and Drug Administration. Medwatch 2001 [online]. Available from URL: http://www.fda.gov/medwatch/safety/2001/remicade_deardoc.pdf. [Accessed 2003 Sep 15]

  118. Choy EHS, Panyi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001; 344: 907–16

    Article  PubMed  CAS  Google Scholar 

  119. Jarvis B, Faulds D. Etanercept: a review of its use in rheumatoid arthritis. Drugs 1999; 56: 945–66

    Article  Google Scholar 

  120. 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; 337: 141–7

    Article  PubMed  CAS  Google Scholar 

  121. Weinblatt ME, Kremer JM, Bankhurst AD, et al. 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; 340: 253–9

    Article  PubMed  CAS  Google Scholar 

  122. 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; 343: 1586–93

    Article  PubMed  CAS  Google Scholar 

  123. Spencer-Green G, Genovese M, Martin RW, et al. Enbrel® (etanercept) vs methotrexate (MTX) in early rheumatoid arthritis (ERA trial): two-year follow-up [abstract]. J Rheumatol 2001 Jul; 28 Suppl. 63: 106

    Google Scholar 

  124. Genovese M, Martin R, Fleischmann R, et al. Etanercept (Enbrel®) in early erosive rheumatoid arthritis (ERA trial): observations at 3 years [abstract]. Arthritis Rheum 2001 Sep; 44 Suppl. 9: 78

    Google Scholar 

  125. Genovese M, Martin R, Fleischmann R, et al. Etanercept (Enbrel®) in early erosive rheumatoid arthritis (ERA trial): 4-year clinical and radiographic data [abstract]. Ann Rheum Dis 2003; 62 Suppl. 1: 183

    Google Scholar 

  126. 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. TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Lancet 2004 Feb 28; 363(9410): 675–81

    CAS  Google Scholar 

  127. Fleischmann R, Iqbal I, Nandeswar P, et al. Safety and efficacy of disease-modifying antirheumatic drugs: focus on the benefits and risks of etanercept. Drug Saf 2002; 25: 173–97

    Article  PubMed  CAS  Google Scholar 

  128. Khanna D, McMahon M, Furst DE. Safety of tumour necrosis factor-alpha antagonists. Drug Saf 2004; 27(5): 307–24

    Article  PubMed  CAS  Google Scholar 

  129. Keating GM, Jarvis B. Management of rheumatoid arthritis: defining the role of etanercept. Dis Manage Health Outcomes 2002; 10: 17–39

    Article  CAS  Google Scholar 

  130. Cote T. TNF blocker safety: lymphoma and liver failure, Food and Drug Administration, Arthritis Advisory Committee, 2003 Mar 4 [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/03/slides/3930sl.htm [Accessed 2003 Sep23]

  131. Machold KP, Smolen JS. Adalimumab: a new TNF-α antibody for treatment of inflammatory joint disease. Expert Opin Biol Ther 2003; 3: 351–60

    PubMed  CAS  Google Scholar 

  132. Kress S. Food and Drug Administration, Center for Biologies Evaluation and Research. Clinical review. Adalimub: for use in the treatment of rheumatoid arthritis [online]. Available from URL: http://www.fda.gov/cber/review/adalabbl23102rl.htm#viii [Accessed 2003 Sep 22]

  133. Weinblatt MW, Keystone EC, Furst DE, et al. Adalimumab, a fully human-antitumor necrosis factor α monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate. The ARMADA trial. Arthritis Rheum 2003; 48: 35–45

    Article  CAS  Google Scholar 

  134. 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 May; 50(5): 1400–11

    Article  PubMed  CAS  Google Scholar 

  135. van de Putte LB, Atkins C, Malaise M, et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis 2004 May; 63(5): 508–16

    Article  PubMed  CAS  Google Scholar 

  136. Furst DE, Schiff MH, Fleischmann RM, et al. Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis). J Rheumatol 2003 Dec; 30(12): 2563–71

    PubMed  CAS  Google Scholar 

  137. Arend WP, Welgus HG, Thopson RC, et al. Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist. J Clin Invest 1990; 85: 1694–7

    Article  PubMed  CAS  Google Scholar 

  138. Cvetkovic RS, Keating G. Anakinra. Biodrugs 2002; 16: 303–11

    Article  PubMed  CAS  Google Scholar 

  139. The European Agency for the Evaluation of Medicinal Products. Kineret European Assessment report: scientific discussion [online]. Available from URL: http://www.eudra.org/humandocs/Humans/EPAR/kineret/kinerethtm [Accessed 2003 Sep 24]

  140. Food and Drug Administration. Arthritis Drugs Advisory Committee [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/01/briefing/3779bl.htm [Accessed 2003 Sep 25]

  141. Cohen SB, Moreland LW, Cush JJ, et al. A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate. 990145 Study Group. Ann Rheum Dis 2004 Sep; 63(9): 1062–8

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  143. Fleischmann RM, Schlechtman J, Bennett R, et al. Anakinra a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1RA) in patients with rheumatoid arthritis. Arthritis Rheum 2003; 48: 927–34

    Article  PubMed  CAS  Google Scholar 

  144. Schiff M, Bulpitt K, Weaver A, et al. Safety of combination therapy with Kineret™ (anakinra) and etanercept in patients with rheumatoid arthritis [abstract]. Arthritis Rheum 2001; 44 Suppl.: S79

    Google Scholar 

  145. Fleischmann RM. Addressing the safety of anakinra in patients with rheumatoid arthritis. Rheumatology 2003; 42 Suppl. 2: ii29–35

    Article  PubMed  CAS  Google Scholar 

  146. The European Agency for the Evaluation of Medicinal Products. Post-authorisation evaluation of medicines for human use-EMEA Public Statement: increased risk of serious infection and neutropenia in patients treated concurrently with Kineret (anakinra) and Enbrel (etanercept) [online]. Available from URL: http://www.emea.eu.int/pdfs/human/press/pus/3163102en.pdf [Accessed 2003 Oct 19]

  147. Maetzel A, Strand V, Tugwell P, et al. Economic comparison of leflunomide and methotrexate in patients with rheumatoid arthritis: an evaluation based on a 1-year randomised controlled trial. Pharmacoeconomics 2002; 20(1): 61–70

    Article  PubMed  CAS  Google Scholar 

  148. Choi HK, Seeger JD, Kuntz KM. A costs-effectiveness analysis of treatment options for patients with methotrexate-naive rheumatoid arthritis. J Rheumatol 2002; 29: 1156–65

    PubMed  Google Scholar 

  149. Yazdani C, McLaughlin T, Cummins G, et al. Comparison of rheumatoid arthritis care costs in patients starting therapy with leflunomide versus etanercept. Am J Manag Care 2001; 7 (13 Suppl.): S419–26

    PubMed  CAS  Google Scholar 

  150. Maetzel A, Strand V, Tugwell P, et al. Cost effectiveness of adding leflunomide to a 5-year strategy of conventional disease-modifying antirheumatic drugs in patients with rheumatoid arthritis. Arthritis Rheum 2002; 47: 655–61

    Article  PubMed  Google Scholar 

  151. Maetzel A, Bombardier C, Strand V, et al. How US and Canadian rheumatologists treat moderate or aggressive rheumatoid arthritis. J Rheumatol 1998; 25: 2331–8

    PubMed  CAS  Google Scholar 

  152. Welsing PMJ, Severens JL, Hartman M, et al. Modelling study into cost-effectiveness over 5 year of treatment strategies including TNF-blocking treatment and leflunomide in the Netherlands [abstract]. Ann Rheum Dis 2003; 62 Suppl. 1: 108

    Article  Google Scholar 

  153. Verhoeven AC, Bibo JC, Boers M, et al. Cost-effectiveness and cost-utility of combination therapy in early rheumatoid arthritis: randomized comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone. COBRA trial group. Br J Rheumatol 1998; 37: 1102–9

    CAS  Google Scholar 

  154. Korthals-de Bos IBC, van Tulder MW, Boers M, et al. Indirect and total costs of early rheumatoid arthritis: a randomized comparison of combined step-down prednisolone, methotrexate and sulfasalazine with sulfasalazine alone. J Rheumatol 2004; 31: 1709–16

    PubMed  CAS  Google Scholar 

  155. Landewe RB, Boers M, Verhoeven AC, et al. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum 2002; 46: 347–56

    Article  PubMed  CAS  Google Scholar 

  156. Choi HK, Seeger JD, Kuntz KM. A costs-effectiveness analysis of treatment options for patients with methotrexate-resistant rheumatoid arthritis. Arthritis Rheum 2000; 43: 2316–27

    Article  PubMed  CAS  Google Scholar 

  157. Tugwell P, Pincus T, Yocum D, et al. Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis: the Methotrexate-Cyclosporine Combination Study Group. N Engl J Med 1995; 333: 137–41

    Article  PubMed  CAS  Google Scholar 

  158. O’Dell JR, Haire C, Erikson N, et al. Efficacy of triple DMARD therapy in patients with RA with suboptimal response to methotrexate. J Rheumatol Suppl 1996; 44: 72–4

    Google Scholar 

  159. Moreland LW, Schiff MH, Baumgartner SW, et al. Etanercept therapy in rheumatoid arthritis: a randomized, controlled trial. Ann Intern Med 1999; 130: 478–86

    PubMed  CAS  Google Scholar 

  160. Kavanaugh A, Heudebert G, Cush J, et al. Cost evaluation of novel therapeutics in rheumatoid arthritis (CENTRA): a decision analysis model. Semin Arthritis Rheum 1996; 25: 297–307

    Article  PubMed  CAS  Google Scholar 

  161. Yelin E, Wanke LA. An assessment of the annual and long-term direct costs of rheumatoid arthritis: the impact of poor function and functional decline. Arthritis Rheum 1999; 42: 1209–18

    Article  PubMed  CAS  Google Scholar 

  162. Kobelt G, Eberhardt K, Jonsson L, et al. Economic consequences of the progression of rheumatoid arthritis in Sweden. Arthritis Rheum 1999; 42: 347–56

    Article  PubMed  CAS  Google Scholar 

  163. Chiou CF, Wanke LA, Reyes C, et al. A cost-efficacy comparison of biologic agents in the treatment of rheumatoid arthritis [abstract]. Ann Rheum Dis 2003; 62 Suppl. 1: 353

    Article  Google Scholar 

  164. Leardini G, Ganguly R, Singh A. Cost-effectiveness analysis of etanercept versus infliximab and anakinra in the treatment of rheumatoid arthritis in Italy [abstract]. Arthritis Rheum 2003; 48 (9 Suppl.): S460

    Article  CAS  Google Scholar 

  165. Chiou CF, Wanke LA, Reyes C, et al. Comparison of the cost-efficacy in the treatment of rheumatoid arthritis [abstract]. Arthritis Rheum 2003; 48 (9 Suppl.): S263

    Google Scholar 

  166. Singh A, Wanke LA, Malone DC, et al. Cost-efficacy comparison of adalimumab and etanercept in the treatment of rheumatoid arthritis [abstract]. Arthritis Rheum 2003; 48 (9 Suppl.): S461

    Article  Google Scholar 

  167. Bansback NJ, Brennan A, Sengupta N, et al. Cost effectiveness of adalimumab (Humira™) in the treatment of patients with moderate to severe rheumatoid arthritis (RA) [abstract]. Arthritis Rheum 2003; 48 (9 Suppl.): S215

    Google Scholar 

  168. Kobelt G, Jonsson L, Young A, et al. The cost-effectiveness of infliximab (Remicade®) in the treatment of rheumatoid arthritis in Sweden and the United Kingdom based on the ATTRACT study. Rheumatology 2003; 42: 326–35

    Article  PubMed  CAS  Google Scholar 

  169. Wong JB, Singh G, Kavanaugh A. Estimating the cost-effectiveness of 54 weeks of infliximab for rheumatoid arthritis. Am J Med 2002; 113: 400–8

    Article  PubMed  Google Scholar 

  170. Nuijten MJC, Engelfriet P, Duijn K, et al. A cost-cost study comparing etanercept with infliximab in rheumatoid arthritis. Pharmacoeconomics 2001; 19: 1051–64

    Article  PubMed  CAS  Google Scholar 

  171. Young A, Dixey J, Cox N, et al. How does functional disability in early rheumatoid arthritis (RA) affect patients and their lives? Results from a 5 year follow-up in 732 patients from the Early RA Study (ERAS). Rheumatology (Oxford) 2000 Jun; 39 (6): 603–11

  172. Lindkvist E, Saxne T, Geborek P, et al. Ten-year outcome in a cohort of early rheumatoid arthritis patients-health status, disease process and damage. Ann Rheum Dis 2002; 61: 1055–9

    Article  Google Scholar 

  173. Wong JB, Davis GL, Pauker SG. Cost effectiveness of ribavirin/ interferon alfa-2b after interferon relapse in chronic hepatitis C. Am J Med 2000; 108: 366–73

    Article  PubMed  CAS  Google Scholar 

  174. Geborek P, Crnkic M, Pterson IF, et al. South Swedish Arthritis Treatment Group. Etanercept, infliximab, and leflunomide in established rheumatoid arthritis: clinical experience using a structured follow up programme in southern Sweden. Ann Rheum Dis 2002; 61: 793–8

    CAS  Google Scholar 

  175. Malone DC, Ortmeier BG. Cost effectiveness analysis of etanercept versus infliximab in the treatment of rheumatoid arthritis patients. Ann Rheum Dis 2003; 62 Suppl. 1: 353

    Article  Google Scholar 

  176. Den Breeder AA, Creemers MCW, van Gestel AM, et al. Dose titration using the disease activity score (DAS28) in rheumatoid arthritis in patients treated with TNFα. Rheumatology 2002; 41: 638–42

    Article  Google Scholar 

  177. Bresnihan B, Chan WW, Woolley DM. Productivity improvement in patients with rheumatoid arthritis receiving anakinra treatment [abstract]. Ann Rheum Dis 2002; 61 Suppl. 1: 182

    Article  Google Scholar 

  178. Guh DP, Marra CA, Woolcott JC, et al. Cost-effectiveness of anakinra plus methotrexate verus methotrexate alone for the treatment of rheumatoid arthritis [abstract]. Arthritis Rheum 2003; 48 (9 Suppl.): S264

    Google Scholar 

  179. Choi HK, Hernan MA, Seeger JD, et al. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002; 359: 1173–7

    Article  PubMed  CAS  Google Scholar 

  180. De Vries-Bouwstra JK, Goekoop-Ruiterman YPM, Breedveld FC, et al. Clinical and radiological outcomes after one-year follow-up of the BEST study, a randomized trial comparing four different strategies in early rheumatoid arthritis [abstract no. LB 18]. ACR/ ARHP 67th Annual Scientific Meeting; 2003 Oct 23–28; Orlando (FL) [online]. Available from URL: http://www.abstractsonline.com/viewer/searchAdvancedResults.asp [Accessed 2003 Oct 11]

  181. Cannon GW, Starnd V, Scarazzini L, et al. Comparison of adverse event reporting rates for etanercept, infliximab, leflunomide and methotrexate [abstract]. Arthritis Rheum 2003; 48 (9 Suppl.): S242

    Google Scholar 

  182. Gabriel SE, Crowson CS, Luthra HS. Modeling lifetime costs of rheumatoid arthritis. J Rheumatol 1999; 26: 1269–74

    PubMed  CAS  Google Scholar 

  183. Gabriel SE, Coyle D, Moreland LW. A clinical and economic review of disease modifying antirheumatic drugs. Pharmacoeconomics 2001; 19: 715–28

    Article  PubMed  CAS  Google Scholar 

  184. Pressman Lovinger S. Use of biologics for rheumatoid arthritis tempered by concerns over safety, cost. JAMA 2003; 289: 3229–30

    Article  PubMed  Google Scholar 

  185. Wolbink G, de Groot E, Lems W, et al. Relation between serum levels of infliximab, C-reactive protein and clinical response to infliximab in patients with rheumatoid arthritis [abstract]. Arthritis Rheum 2003; 48 (9 Suppl.): S136

    Google Scholar 

  186. NIPO-rapport. Knelpunten bij de behandeling van reumatoide artritis. (B2460). Amsterdam: NIPO Amsterdam, 2002 Oct

    Google Scholar 

  187. Brocq O, Plubel Y, Breuil V, et al. Etanercept: infliximab switch in rheumatoid arthritis 14 out of 131 patients treated with anti TNF alpha. Presse Med 2002; 31: 1836–9

    PubMed  CAS  Google Scholar 

  188. Buch MH, Bingham SJ, Bejarano V, et al. Do patients with rheumatoid arthritis demonstrate an improvement on etanercept following an inadequate response to infliximab [abstract]. Arthritis Rheum 2003; 48 (9 Suppl.): S325

    Article  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Department of Rheumatology, VU University Medical Centre, Room 4A40, PO Box 7057, Amsterdam, The Netherlands

    Michael T. Nurmohamed & Ben A. C. Dijkmans

  2. Jan van Breemen Institute, Amsterdam, The Netherlands

    Michael T. Nurmohamed & Ben A. C. Dijkmans

  3. Slotervaart Hospital, Amsterdam, The Netherlands

    Ben A. C. Dijkmans

Authors
  1. Michael T. Nurmohamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ben A. C. Dijkmans
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael T. Nurmohamed.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nurmohamed, M.T., Dijkmans, B.A.C. Efficacy, Tolerability and Cost Effectiveness of Disease-Modifying Antirheumatic Drugs and Biologic Agents in Rheumatoid Arthritis. Drugs 65, 661–694 (2005). https://doi.org/10.2165/00003495-200565050-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200565050-00006

Keywords

Search

Navigation