Combination therapy

  • Ernest Choy
  • Harold E. Paulus
Part of the Progress in Inflammation Research book series (PIR)


Clinicians who treat rheumatoid arthritis (RA) always have utilized all of the therapeutic modalities available to improve the outcomes of patients with a chronic disabling disease that only rarely exhibits a sustained treatment-induced remission. As new treatments have been developed, they have been tried and added to existing therapies [1]. Narcotic analgesics were supplemented with salicylates, and later with corticosteroids. Early disease modifying anti-rheumatic drugs (DMARDs) such as anti malarial drugs and parenteral gold compounds were added to these ”background” therapies, and in controlled clinical trials, their addition proved more beneficial than the addition of placebo. However, because the benefit of these treatments is associated with varying degrees of suppression of (rheumatoid) inflammation, adverse effects are frequently associated with concomitant suppression of normal protective immune and inflammatory mechanisms. Patients recognize that increased benefit is frequently associated with increased side effects. Consequently, they are anxious to try complementary and alternative medications that promise fewer side effects, and are willing to try new drugs and combinations of drugs that may have a more favorable benefit/risk ratio.


Rheumatoid Arthritis Early Rheumatoid Arthritis Combination Therapy Group ACR20 Response Established Rheumatoid Arthritis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Paulus HE (1996) History of combination therapy of rheumatoid arthritis. J Rheumatology (Suppl) 44: 38–42Google Scholar
  2. 2.
    Michotte L, Vanstype J (1959) The influence of chrysotherapy followed by chloroquine therapy upon the hemagglutination reaction in rheumatoid arthritis. Acta Rheumatol Scand 5: 148CrossRefGoogle Scholar
  3. 3.
    Sievers K, Hurri L (1963) Combined therapy of rheumatoid arthritis with gold and chloroquine. Evaluation of the therapeutic effect. Acta Rheumatol Scand 9: 48–55CrossRefPubMedGoogle Scholar
  4. 4.
    Lockie LM, Norcross BM (1966) Salicylates, phenylbutazone, chloroquines and indomethacin in treatment of rheumatoid arthritis. In: JL Hollander (ed): Arthritis and Allied Conditions. Lea and Febiger, Philadelphia, 333–348Google Scholar
  5. 5.
    McCarty DJ, Carrera GF (1982) Intractable rheumatoid arthritis. Treatment with combined cyclophosphamide, azathioprine, and hydroxychloroquine. JAMA 248: 1718–1723CrossRefPubMedGoogle Scholar
  6. 6.
    Csuka M, Carrera GF, McCarty DJ (1986) Treatment of intractable rheumatoid arthritis with combined cyclophosphamide, azathioprine, and hydroxychloroquine. A followup study. JAMA 255: 2315–2319CrossRefPubMedGoogle Scholar
  7. 7.
    Bunch TW, O’Duffy JD, Tompkins RB, OTallon WM (1984) Controlled trial of hydroxychloroquine and D-penicillamine singly and in combination in the treatment of rheumatoid arthritis. Arthritis Rheum 27: 267–276CrossRefPubMedGoogle Scholar
  8. 8.
    Gibson TG, Emery P, Armstrong RD, Crisp AJ, Panayi GS (1987) Combined D-penicillamine and Chloroquine treatment — A comparative study. Br J Rheumatol 26: 279–284CrossRefPubMedGoogle Scholar
  9. 9.
    McKenna F, Hopkins R, Hinchcliffe KP (1985) Gold and penicillamine, alone and in combination in active rheumatoid arthritis. 16th International Congress of Rheumatology (abstract)Google Scholar
  10. 10.
    Scott DL, Dawes PT, Tunn E, Fowler PD, Shadforth MF, Fisher J et al (1989) Combination therapy with gold and hydroxychloroquine in rheumatoid arthritis: A prospective, randomized, placebo-controlled study. Br J Rheumatol 28: 128–133CrossRefPubMedGoogle Scholar
  11. 11.
    Maini RN, Breedveld FC, Kalden JR, Smolen JS, Davis D, Macfarlane JD et al (1998) Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor a monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 41: 1552–1563CrossRefPubMedGoogle Scholar
  12. 12.
    Boers M, Ramsden M (1991) Long acting drug combinations in rheumatoid arthritis: a formal overview. J Rheumatol 18: 316–324PubMedGoogle Scholar
  13. 13.
    Oxman AD, Guyatt GH (1988) Guidelines for reading literature reviews. CMAJ Can Med Assoc J 138: 697–703Google Scholar
  14. 14.
    Williams HJ, Ward JR, Reading JC, Brooks RH, Clegg DO, Skosey JL et al (1992) Comparison of auranofin, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum 35: 259–269CrossRefPubMedGoogle Scholar
  15. 15.
    Luthra HS. Midwest Cooperative Rheumatic Disease Study Group (1990) Double-blind study comparing auranofin and hydroxychloroquine alone and in combination in rheumatoid arthritis. Arthritis Rheum 33 (Suppl): S25Google Scholar
  16. 16.
    Willkens RF, Urowitz MB, Stablein DM, McKendry RJ Jr., Berger RG et al (1992) Comparison of azathioprine, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum 35: 849–856CrossRefPubMedGoogle Scholar
  17. 17.
    Clegg DO, Dietz F, Duffy J, Willkens RF, Hurd E, Germain BF et al (1997) Safety and efficacy of hydroxychloroquine as maintenance therapy for rheumatoid arthritis after combination therapy with methotrexate and hydroxychloroquine. J Rheumatol 24: 1896–1902PubMedGoogle Scholar
  18. 18.
    Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R, van Denderen JC et al (1997) Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 350: 309–318CrossRefPubMedGoogle Scholar
  19. 19.
    Anderson JJ, Wells G, Verhoeven AC, Felson DT (2000) Factors predicting response to treatment in rheumatoid arthritis: The importance of disease duration. Arthritis Rheum 43: 22–29CrossRefPubMedGoogle Scholar
  20. 20.
    Albert DA, Aksentijevich S, Hurst S, Fries JF, Wolfe F (2000) Modeling therapeutic strategies in rheumatoid arthritis: use of decision analysis and Markov models. J Rheumatol 27: 644–652PubMedGoogle Scholar
  21. 21.
    Scott DL, Symmons DP, Coulton BL, Popert AJ (1987) Long-term outcome of treating rheumatoid arthritis: results after 20 years. Lancet 1: 1108–1111CrossRefPubMedGoogle Scholar
  22. 22.
    van der Heijde DM, van Leeuwen MA, van Riel PL, Koster AM, van’ t Ho, MA et al (1992) Biannual radiographic assessments of hands and feet in a three-year prospective follow-up of patients with early rheumatoid arthritis. Arthritis Rheum 35: 26–34CrossRefPubMedGoogle Scholar
  23. 23.
    Emery P, Breedveld FC, Dougados M, Kalden JR, Schiff MH, Smolen JS (2002) Early referral recommendation for newly diagnosed rheumatoid arthritis: Evidence based development of a clinical guide. Ann Rheum Dis 61: 290–297CrossRefPubMedGoogle Scholar
  24. 24.
    Kirwan JR (1995) The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. N Engl J Med 333: 142–146CrossRefPubMedGoogle Scholar
  25. 25.
    van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW (2002) Lowdose 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 Internal Med 136: 1–12Google Scholar
  26. 26.
    Hickling P, Jacoby RK, Kirwan JR (1998) Joint destruction after glucocorticoids are withdrawn in early rheumatoid arthritis. Arthritis and Rheumatism Council Low Dose Glucocorticoid Study Group. Br J Rheumatol 37: 930–936CrossRefPubMedGoogle Scholar
  27. 27.
    Landewe RB, Boers M, Verhoeven AC, Westhovens R, van de Laar MA, Markusse HM et al (2002) COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum 46: 347–356CrossRefPubMedGoogle Scholar
  28. 28.
    Verhoeven AC, Bibo JC, Boers M, Engel GL, van der Linden S (1998) 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. Combinatietherapie Bij Reumatoide Artritis. Br J Rheumatol 37: 1102–1109CrossRefPubMedGoogle Scholar
  29. 29.
    Mottonen T, Hannonen P, Leirisalo-Repo M, Nissila M, Kautiainen H, Korpela M et al (1999) Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: A randomised trial. FIN-RACo trial group. Lancet 353: 1568–1573CrossRefPubMedGoogle Scholar
  30. 30.
    Mottonen T, Hannonen P, Korpela M, Nissila M, Kautiainen H, Honen J et al (2002) Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis. Arthritis Rheum 46: 894–898CrossRefPubMedGoogle Scholar
  31. 31.
    Dougados M, Combe B, Cantagrel A, Goupille P, Olive P, Schattenkirchner M et al (1999) Combination therapy in early rheumatoid arthritis: A randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components. Ann Rheum Dis 58: 220–225CrossRefPubMedGoogle Scholar
  32. 32.
    Proudman SM, Conaghan PG, Richardson C, Griffiths B, Green MJ, McGonagle D et al (2000) Treatment of poor-prognosis early rheumatoid arthritis. A randomized study of treatment with methotrexate, cyclosporin A, and intraarticular corticosteroids compared with sulfasalazine alone. Arthritis Rheum 43: 1809–1819CrossRefPubMedGoogle Scholar
  33. 33.
    Marchesoni A, Battafarano N, Arreghini M, Panni B, Cagnoli M, Tosi S (2001) Slower radiographic progression in patients with early rheumatoid arthritis treated with cyclosporin and methotrexate combination therapy. Arthritis Rheum 44 (Suppl. 9): S371Google Scholar
  34. 34.
    Ferraccioli GF, Gremese E, Tomietto P, Favret G, Damato R, Di Poi E (2002) Analysis of improvements, full responses, remission and toxicity in rheumatoid patients treated with step-up combination therapy (methotrexate, cyclosporin A, sulphasalazine) or monotherapy for three years. Rheumatology 41: 892–898CrossRefPubMedGoogle Scholar
  35. 35.
    Porter DR, Capell HA, Hunter J (1993) Combination therapy in rheumatoid arthritis— no benefit of addition of hydroxychloroquine to patients with a suboptimal response to intramuscular gold therapy. J Rheumatol 20: 645–649PubMedGoogle Scholar
  36. 36.
    Faarvang KL, Egsmose C, Kryger P, Podenphant J, Ingeman-Nielsen M, Hansen TM (1993) Hydroxychloroquine and sulphasalazine alone and in combination in rheumatoid arthritis: a randomised double blind trial. Ann Rheum Dis 52: 711–715CrossRefPubMedGoogle Scholar
  37. 37.
    Willkens RF, Sharp JT, Stablein D, Marks C, Wortmann R (1995) Comparison of azathioprine, methotrexate, and the combination of the two in the treatment of rheumatoid arthritis. A forty-eight-week controlled clinical trial with radiologic outcome assessment. Arthritis Rheum 38: 1799–1806CrossRefPubMedGoogle Scholar
  38. 38.
    Trnavsky K, Gatterova J, Linduskova M, Peliskova Z (1993) Combination therapy with hydroxychloroquine and methotrexate in rheumatoid arthritis. itZeitschrift fur Rheumatologie 52: 292–296Google Scholar
  39. 39.
    Ferraz MB, Pinheiro GR, Helfenstein M, Albuquerque E, Rezende C, Roimicher L et al (1994) Combination therapy with methotrexate and chloroquine in rheumatoid arthritis. A multicenter randomized placebo-controlled trial. Scand J Rheumatol 23: 231–236CrossRefPubMedGoogle Scholar
  40. 40.
    O’Dell JR, Haire CE, Erikson N, Drymalski W, Palmer W, Eckhoff PJ et al (1996) Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med 334: 1287–1291CrossRefPubMedGoogle Scholar
  41. 41.
    O’Dell JR, Leff R, Paulsen G, Haire C, Mallek J, Eckhoff PJ et al (2002) Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: Results of a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 46: 1164–1170CrossRefPubMedGoogle Scholar
  42. 42.
    Tugwell P, Pincus T, Yocum D, Stein M, Gluck O, Kraag G et al (1995) Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The Methotrexate-Cyclosporine Combination Study Group. N Engl J Med 333: 137–141CrossRefPubMedGoogle Scholar
  43. 43.
    Pascalis L, Aresu G, Pia G (1999) Long-term efficacy and toxicity of cyclosporin A + fluocortolone + methotrexate in the treatment of rheumatoid arthritis. Clin Exp Rheumatol 17: 679–688PubMedGoogle Scholar
  44. 44.
    Gonzalez-Gay MA, Blanco R, Garcia-Porrua C, Ibanez D, Vazquez-Caruncho M, Sanchez-Burson J et al (1998) Long-term follow up of patients receiving combined therapy with cyclosporine and methotrexate. Arthritis Rheum 41: 1703–1704CrossRefPubMedGoogle Scholar
  45. 45.
    Stein CM, Pincus T, Yocum D, Tugwell P, Wells G, Gluck O et al (1997) Combination treatment of severe rheumatoid arthritis with cyclosporine and methotrexate for fortyeight weeks: An open-label extension study. The Methotrexate-Cyclosporine Combination Study Group. Arthritis Rheum 40: 1843–1851CrossRefPubMedGoogle Scholar
  46. 46.
    Kremer JM, Genovese MC, Cannon GW, Caldwell JR, Cush JJ, Furst DE et al (2002) Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. A randomized, double-blind, placebo-controlled trial. Ann Internal Med 137: 726–733Google Scholar
  47. 47.
    Weinblatt ME, Kremer JM, Coblyn JS, Maier AL, Helfgott SM, Morrell M et al (1999) Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis. Arthritis Rheum 42: 1322–1328CrossRefPubMedGoogle Scholar
  48. 48.
    Lehman AJ, Esdaile JM, Klinkhoff A, Schulzer M, Grant E, Fitzgerald A (2002) A 48-week randomized double-blind double-observer placebo-controlled multicentre trial of intramuscular gold in combination with methotrexate in rheumatoid arthritis. Arthritis Rheum 46 (Suppl 9): S204Google Scholar
  49. 49.
    Furst DE, Saag K, Fleischmann MR, Sherrer Y, Block JA, Schnitzer T et al (2002) Efficacy of tacrolimus in rheumatoid arthritis patients who have been treated unsuccessfully with methotrexate: a six-month, double-blind, randomized, dose-ranging study. Arthritis Rheum 46: 2020–2028CrossRefPubMedGoogle Scholar
  50. 50.
    Kremer J, Habros J, Kolba K, Kaine J, Borton MA, Mekki Q et al (2002) Combination treatment with tacrolimus (Prograf; FK506) and methotrexate (MTX) in rheumatoid arthritis patients who are partial responders to methotrexate. Arthritis Rheum 46 (Suppl 9): S515Google Scholar
  51. 51.
    Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox et al (1999) A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 340: 253–259CrossRefPubMedGoogle Scholar
  52. 52.
    Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR et al (2000) Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 343: 1594–1602CrossRefPubMedGoogle Scholar
  53. 53.
    Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA et al (2003) Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: The ARMADA trial. Arthritis Rheum 48: 35–45CrossRefPubMedGoogle Scholar
  54. 54.
    Cohen S, Hurd E, Cush J, Schiff M, Weinblatt ME, Moreland LW et al (2002) Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: Results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 46: 614–624CrossRefPubMedGoogle Scholar
  55. 55.
    Smolen J et al (2003) Active-controlled study of patients receiving infliximab for the treatment of RA of early onset. The ASPIRE trial. EULAR 2003, Lisbon, Portugal, Abstract OP0001Google Scholar
  56. 56.
    Klareskog L et al (2003) Satellite Symposium: New perspectives on treatment expectations in rheumatoid arthritis; efficacy and tolerability. Evolving expectations for biological therapy in rheumatoid arthritis. EULAR 2003, Lisbon, PortugalGoogle Scholar
  57. 57.
    Combe BG, Codreanu C, Fiocco U, Gaubitz M, Geusens PP, Kvien TK et al (2002) Dou-ble-blind comparison of etanercept and sulfasalazine, alone and combined in patients with active rheumatoid arthritis. Arthritis Rheum 46 (Suppl): S517Google Scholar
  58. 58.
    Temekonidis TI, Georgiadis AN, Alamanos Y, Bougias DV, Voulgari PV, Drosos AA (2003) Infliximab treatment in combination with cyclosporin A in patients with severe refractory rheumatoid arthritis. Ann Rheum Dis 61: 822–825CrossRefGoogle Scholar
  59. 59.
    Kiely PD, Johnson DM (2002) Infliximab and leflunomide combination therapy in rheumatoid arthritis: an open-label study. Rheumatology 41: 631–637CrossRefPubMedGoogle Scholar
  60. 60.
    Bingham SJ, Barcelos A, Buch MH, Lindsay S, Emery P (2002) Induction of serological lupus in patients on leflunomide and infliximab. Arthritis Rheum 46 (Suppl 9): S168Google Scholar
  61. 61.
    Edwards JC, Szczepanski L, Scechinski J, Filipowicz-Sosnowska A, Close D, Stevens RM et al (2002) Efficacy and safety of rituximab, a B-Cell targeted chimeric monoclonal antibody: A randomized, placebo-controlled trial in patients with rheumatoid arthritis. Arthritis Rheum 46 (Suppl): S197Google Scholar
  62. 62.
    Schiff MH, Bulpitt K, Weaver AA, Genovese MC, Cohen S, Furst D et al (2001) Safety of combination therapy with anakinra and etanercept in patients with rheumatoid arthritis. Arthritis Rheum 44 (Suppl): S–79Google Scholar
  63. 63.
    Marinova-Mutafchieva L, Williams RO, Mauri C, Mason LJ, Walmsley MJ, Taylor PC et al (2000) A comparative study into the mechanisms of action of anti-tumor necrosis factor alpha, anti-CD4, and combined anti-tumor necrosis factor alphaJanti-CD4 treatment in early collagen-induced arthritis. Arthritis Rheum 43: 638–644CrossRefPubMedGoogle Scholar
  64. 64.
    Moreland LW, Alten R, Van den BF, Appelboom T, Leon M, Emery P et al (2002) Costimulatory blockade in patients with rheumatoid arthritis: A pilot, dose-finding, doubleblind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis Rheum 46: 1470–1479CrossRefPubMedGoogle Scholar
  65. 65.
    Weinblatt M, Schiff M, Goldman M, Kremer J, Breazna A, Becker JC (2002) A pilot, multi-center, randomized, double-blind, placebo controlled trial of a co-stimulation blocker CTLA4Ig (2 mgJkg) given monthly in combination with etanercept in active rheumatoid arthritis. Arthritis Rheum 46 (Suppl 9): S204Google Scholar
  66. 66.
    Verhoeven AC, Boers M, Tugwell P (1998) Combination therapy in rheumatoid arthritis: updated systematic review. Br J Rheumatol 37: 612–619CrossRefPubMedGoogle Scholar
  67. 67.
    Williams RO, Mauri C, Mason LJ, Marinova-Mutafchieva L, Ross SE, Feldman M et al (1998) Therapeutic actions of cyclosporine and anti-tumor necrosis factor alpha in collagen-induced arthritis and the effect of combination therapy. Arthritis Rheum 41: 1806–1812CrossRefPubMedGoogle Scholar
  68. 68.
    Brahn E, Peacock DJ, Banquerigo ML (1991) Suppression of collagen-induced arthritis by combination cyclosporin A and methotrexate therapy. Arthritis Rheum 34: 1282–1288CrossRefPubMedGoogle Scholar
  69. 69.
    Munster T, Furst DE (1999) Pharmacotherapeutic strategies for disease-modifying antirheumatic drug (DMARD) combinations to treat rheumatoid arthritis (RA). Clin Exp Rheumatol 17 (6 Suppl 18): S29–S36PubMedGoogle Scholar
  70. 70.
    Choy EH, Smith C, Scott DL (2002) A meta-analysis of the efficacy and toxicity of combining disease modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). Arthritis Rheum 46 (Suppl 9): S170Google Scholar
  71. 71.
    American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the Management of Rheumatoid Arthritis (2002) Arthritis Rheum 46: 328–346CrossRefGoogle Scholar
  72. 72.
    van den Borne BE, Landewe RB, Goei The HS, Rietveld JH, Zwinderman AH, Bruyn GA et al (1998) Combination therapy in recent onset rheumatoid arthritis: A randomized double blind trial of the addition of low dose cyclosporine to patients treated with low dose chloroquine. J Rheumatol 25: 1493–1498PubMedGoogle Scholar
  73. 73.
    Haagsma CJ, van Riel PL, de Jong AJ, van de Putte LB (1997) Combination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: A randomized, controlled, double-blind, 52 week clinical trial. Br J Rheumatol 36: 1082–1088CrossRefPubMedGoogle Scholar
  74. 74.
    Gough A, Sheeran T, Arthur V, Panayi G, Emery P (1994) Adverse interaction between intramuscular methylprednisolone and sulphasalazine in patients with early rheumatoid arthritis. A pilot study. Scand J Rheumatol 23: 46–48CrossRefPubMedGoogle Scholar
  75. 75.
    Yasuda M, Sakai K, Oribe M, Yoshioka K, Takahashi H, Ohtsuka E et al (1994) Efficacy of additive DMARD therapy in patients with rheumatoid arthritis. Double blind controlled trial using bucillamine and placebo with maintenance doses of gold sodium thiomalate. J Rheumatol 21: 44–50PubMedGoogle Scholar
  76. 76.
    Bendix G, Bjelle A (1996) Adding low-dose cyclosporin A to parenteral gold therapy in rheumatoid arthritis: A double-blind placebo-controlled study. Br J Rheumatol 35: 1142–1149CrossRefPubMedGoogle Scholar
  77. 77.
    Calguneri M, Pay S, Caliskaner Z, Apras S, Kiraz S, Ertenli I et al (1999) Combination therapy versus monotherapy for the treatment of patients with rheumatoid arthritis. Clin Exp Rheumatol 17: 699–704PubMedGoogle Scholar
  78. 78.
    Ciconelli RM, Ferraz MB, Visioni RA, Oliveira LM, Atra E (1996) A randomized double-blind controlled trial of sulphasalazine combined with pulses of methylprednisolone or placebo in the treatment of rheumatoid arthritis. Br J Rheumatol 35: 150–154CrossRefPubMedGoogle Scholar
  79. 79.
    Corkill MM, Kirkham BW, Chikanza IC, Gibson TG, Panayi GS (1990) Intramuscular depot methylprednisolone induction of chrysotherapy in rheumatoid arthritis: A 24-week randomised controlled trial. Br J Rheumatol 29: 274–279CrossRefPubMedGoogle Scholar
  80. 80.
    van Gestel AM, Laan RF, Haagsma CJ, van de Putte LB, van Riel PL (1995) Oral steroids as bridge therapy in rheumatoid arthritis patients starting with parenteral gold. A randomized double-blind placebo-controlled trial. Br J Rheumatol 34: 347–351CrossRefPubMedGoogle Scholar
  81. 81.
    van Der Veen MJ, Bijlsma JW (1993) The effect of methylprednisolone pulse therapy on methotrexate treatment of rheumatoid arthritis. Clin Rheumatol 12: 500–505CrossRefPubMedGoogle Scholar
  82. 82.
    Wong CS, Champion G, Smith MD, Soden M, Wetherall M, Geddes RA et al (1990) Does steroid pulsing influence the efficacy and toxicity of chrysotherapy? A double blind, placebo controlled study. Ann Rheum Dis 49: 370–372CrossRefPubMedGoogle Scholar
  83. 83.
    Genovese MC, Cohen S, Moreland L, Lium D, Robbins S, Newmark R, Bekker P (2004) Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum 50: 1412–1419CrossRefPubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2005

Authors and Affiliations

  • Ernest Choy
    • 1
  • Harold E. Paulus
    • 2
  1. 1.Sir Alfred Baring Garrod Clinical Trials Unit, Academic Department of RheumatologyKing’s CollegeLondonUK
  2. 2.Division of RheumatologyUCLA School of MedicineLos AngelesUSA

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