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Ann Rheum Dis 2000;59:468-477 ( June )

Extended report

Aggressive treatment in early rheumatoid arthritis: a randomised controlled trial C H M van Jaarsvelda, J W G Jacobsa, M J van der Veenb, A A M Blaauwa, A A Kruizea, D M Hofmana c, H L M Brusc, G A van Albada-Kuipersd, A H M Heurkensd, E J ter Borge, H C M Haanene, C van Booma-Frankfortf, Y Schenkf, J W J Bijlsmaa, on behalf of the Rheumatic Research Foundation Utrecht, The Netherlands

a Department of Rheumatology and Clinical Immunology, University Medical Centre, PO Box 85500, 3508 GA Utrecht, The Netherlands, b Department of Rheumatology, Hospital Sint Jansdal, PO Box 138, 3840 AC Harderwijk, The Netherlands, c Department of Rheumatology, Hospital Hilversum, PO Box 10016, 1201 DA Hilversum, The Netherlands, d Department of Rheumatology, Eemland Hospital, PO Box 1502, 3800 MB Amersfoort, The Netherlands, e Department of Rheumatology, Sint Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands, f Department of Rheumatology, Diakonessen Hospital, Bosboomstraat 1, 3582 KE Utrecht, The Netherlands

Correspondence to: Dr Jacobs Email: J.W.J.Bijlsma{at}DIGD.AZU.NL

Accepted for publication 12 January 2000

OBJECTIVES---To compare three therapeutic strategies using slow acting antirheumatic drugs (SAARDs) in early rheumatoid arthritis (RA), for their disease modifying properties, toxicity, and lag time until treatment effect.
METHODS---Patients with recent onset RA from six hospitals were randomly assigned to immediate initiation of one of three treatment strategies: (I) a "mild SAARD with a long lag time" (hydroxychloroquine, if necessary replaced by auranofin); (II) a "potent SAARD with a long lag time" (intramuscular gold, if necessary replaced by D-penicillamine); (III) a "potent SAARD with a short lag time" (methotrexate, if necessary replaced by sulfasalazine). Comparisons included two years of follow up.
RESULTS---All SAARD strategies reduced mean disease activity. A greater percentage of patients improved clinically with strategies II and III than with strategy I: percentages of patients improved on joint score with strategies II and III (79% and 82%, respectively), which was statistically different from strategy I (66%). The same was true for remission percentages: 31% and 24% v 16%, respectively). Longitudinal analysis showed significantly less disability with strategy III, and a lower erythrocyte sedimentation rate with strategy II than with strategy I. In addition, radiological damage after one and two years, was significantly lower in strategies II and III (at two years median scores were 11 and 10 v 14 in strategy I, p<0.05). Toxicity was increased in strategy II compared with the other strategies.
CONCLUSION---Strategy III, comprising methotrexate or sulfasalazine, produced the best results weighing effectiveness and toxicity. Strategy I (hydroxychloroquine or auranofin) was slightly less effective, and strategy II (intramuscular gold or D-penicillamine) was associated with increased toxicity.

© 2000 by Annals of the Rheumatic Diseases


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