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73 Current problems in pharmaco-vigilance (Committee on Safety in Medicines and The Medicines Control Agency) September 2000; 26: 13.

74 Schnitzer TJ, Truitt K, Fleischmann R, Dalgin P, Block J, Zeng Q, et al. The safety profile, tolerability, and effective dose range of rofecoxib in the treatment of rheumatoid arthritis. Phase II Rofecoxib Rheumatoid Arthritis Study Group. Clin Ther 1999; 21: 1688-702.

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89 van Jaarsveld CH, Jacobs JW, van der Veen MJ, Blaauw AA, Kruize AA, Hofman DM, et al. Aggressive treatment in early rheumatoid arthritis: a randomised controlled trial. On behalf of the Rheumatic Research Foundation Utrecht, The Netherlands. Ann Rheum Dis 2000; 59: 468-77.

90 Stenger AA, Van Leeuwen MA, Houtman PM, Bruyn GA, Speerstra F, Barendsen BC et al. Early effective suppression of inflammation in rheumatoid arthritis reduces radiographic progression. Br J Rheumatol 1998;37:1157-63. [section 4.3.1] [section 4.3.6]

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98 Gotzsche PC, Hansen M, Stoltenberg M, Svendsen A, Beier J, Faarvang KL et al. Randomized, placebo controlled trial of withdrawal of slow-acting antirheumatic drugs and of observer bias in rheumatoid arthritis. Scan J Rheumatol 1996; 25: 194-9.

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

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103 Asten P, Barrett J, Symmons D. Risk of developing certain malignancies is related to duration of immunosuppressive drug exposure in patients with rheumatic diseases. J Rheumatol 1999; 26: 1705-14.

104 Furst DE, Lindsley H, Baethge B, Botstein GR, Caldwell J, Dietz F et al. Dose-loading with hydroxychloroquine improves the rate of response in early, active rheumatoid arthritis: a randomized, double-blind six-week trial with eighteen-week extension. Arthritis Rheum 1999; 42: 357-65.

105 A randomized trial of hydroxychloroquine in early rheumatoid arthritis: the HERA Study. Am J Med 1995; 98: 156-68.

106 Capell HA. Clinical efficacy of sulphasalazine - a review. Br J Rheumatol 1995; 34 (Suppl 2): 35-9.

107 Weinblatt ME, Reda D, Henderson W, Giobbie-Hurder A, Williams D, Diani A et al. Sulfasalazine treatment for rheumatoid arthritis: a metaanalysis of 15 randomized trials. J Rheumatol 1999; 26: 2123-30.

108 Box SA, Pullar T. Sulphasalazine in the treatment of rheumatoid arthritis. Br J Rheumatol 1997; 36: 382-6.

109 Alarcon GS, Tracy IC, Strand GM, Singh K, Macaluso M. Survival and drug discontinuation analyses in a large cohort of methotrexate treated rheumatoid arthritis patients. Ann Rheum Dis 1995; 54: 708-12

110 van Ede AE, Laan RF, Blom HJ, De Abreu RA, van de Putte LB. Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. Semin Arthritis Rheum 1998; 27: 277-92 [Table 6] [section 4.3.7]

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112 Suarez-Almazor ME, Spooner C, Belseck E. Penicillamine for rheumatoid arthritis (Cochrane Review). In: The Cochrane Library Issue2, 2000. Oxford: Update Software.

113 Suarez-Almazor ME, Spooner C, Belseck E. Azathioprine for rheumatoid arthritis. (Cochrane Review). In: The Cochrane Library Issue2, 2000. Oxford: Update Software.

114 Emery P, Breedveld FC, Lemmel EM, Kaltwasser JP, Dawes PT, Gomor B, et al. A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatol 2000; 39: 655-65.

115 Chaudhuri K, Torley N, Madhok R. Cyclosporin. Disease-modifying anti-rheumatic drugs. Cyclosporin. Br J Rheumatol 1997; 36: 1016-21.

116 Ocular toxicity and hydroxychloroquine: guidelines for screening (replacing RCOphth Guidelines 1993). London: Royal College of Ophthalmologists; 1998.

117 British Society for Rheumatology. National guidelines for the monitoring of second line drugs. London: The Society; 2000.

118 Hydroxychloroquine datasheet. Electronic Medicines Compendium (ABPI). http://Emc.vhn.net/public

119 Bluhm GB, Sharp JT, Tilley BC, Alarcon GS, Cooper SM, Pillemer SR et al. Radiographic results from the Minocycline in Rheumatoid Arthritis (MIRA) Trial. J Rheumatol 1997; 24: 1295-302.

120 Kloppenburg M, Breedveld FC, Terwiel JP, Mallee C, Dijkmans BA. Minocycline in active rheumatoid arthritis. A double-blind, placebo-controlled trial. Arthritis Rheum 1994; 37:629-36.

121 Tilley BC, Alarcon GS, Heyse SP, Trentham DE, Neuner R, Kaplan DA et al. Minocycline in rheumatoid arthritis. A 48-week, double-blind, placebo-controlled trial. MIRA Trial Group. Ann Intern Med 1995; 122:81-9.

122 O'Dell JR, Paulsen G, Haire CE, Blakely K, Palmer W, Wees S et al. Treatment of early seropositive rheumatoid arthritis with minocycline: four-year followup of a double-blind, placebo-controlled trial. Arthritis Rheum 1999;42: 1691-5.

123 Ortiz Z, Shea B, Suarez-Almazor ME, Moher D, Wells GA, Tugwell P. The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxicity in rheumatoid arthritis. A metaanalysis of randomized controlled trials. J Rheumatol 1998; 25: 36-43. [Table 6] [section 4.3.7]

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125 Felson DT, Anderson JJ, Meenan RF. The efficacy and toxicity of combination therapy in rheumatoid arthritis. A meta-analysis. Arthritis Rheum 1994; 37: 1487-91.

126 Willkens RF, Sharp JT, Stablein D, Marks C, Wortmann R. 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 1995; 38: 1799-806.

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128 O'Dell JR, Haire CE, Erikson N, Drymalski W, Palmer W, Eckhoff PJ et al. Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications NEJM1996; 334: 1287-91.

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132 Porter DR, Capell HA, Hunter J. Combination therapy in rheumatoid arthritis--no benefit of addition of hydroxychloroquine to patients with a suboptimal response to intramuscular gold therapy. J Rheumatol. 1993; 20: 645-9.

133 Tugwell P, Pincus T, Yocum D, Stein M, Gluck O, Kraag G et al. Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The Methotrexate-Cyclosporine Combination Study Group. NEJM1995; 333: 137-41.

134 Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M et al Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 1999 Dec 4; 354: 1932-9 [section 4.3.10] [section 4.4]

135 Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. NEJM1999; 340: 253-9.

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