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

  1. Amalia A. van Everdingen, MD;
  2. Johannes W.G. Jacobs, MD, PhD;
  3. Dirk R. Siewertsz van Reesema, MD; and
  4. Johannes W.J. Bijlsma, MD, PhD
  1. From University Medical Center Utrecht, Utrecht; Deventer Hospital, Deventer; and Zutphen Hospital, Zutphen, the Netherlands.

    Abstract

    Background: Oral glucocorticoids combined with disease-modifying antirheumatic drugs are beneficial and retard radiologic joint damage in rheumatoid arthritis.

    Objective: To investigate the clinical efficacy, disease-modifying properties, and side effects of low-dose glucocorticoids as monotherapy for previously untreated patients with early active rheumatoid arthritis.

    Design: 2-year randomized, double-blind, placebo-controlled clinical trial.

    Setting: 2 outpatient rheumatology clinics.

    Patients: 81 patients with early active rheumatoid arthritis who had not been treated with disease-modifying antirheumatic drugs.

    Intervention: 41 patients were assigned to 10 mg of oral prednisone per day, and 40 were assigned to placebo. Nonsteroidal anti-inflammatory drugs were allowed in both groups. After 6 months, sulfasalazine (2 g/d) could be prescribed as rescue medication.

    Measurements: Clinical variables were assessed at baseline and every 3 months; radiologic studies were performed every 6 months. Adverse effects were documented every 3 months.

    Results: In the first 6 months, the prednisone group showed more clinical improvement than the placebo group. This effect was not seen after 6 months except in grip strength and the 28-joint score for tenderness. Use of additional therapies was significantly less common in the prednisone group, particularly in the first 6 months. More than 65% of those who completed the study were not taking sulfasalazine. After month 6, radiologic scores showed significantly less progression in the prednisone group than in the placebo group. No clinically relevant adverse effects were observed, except for a higher incidence of osteoporotic fractures in the prednisone group.

    Conclusions: Prednisone, 10 mg/d, provides clinical benefit, particularly in the first 6 months, and substantially inhibits progression of radiologic joint damage in patients with early active rheumatoid arthritis and no previous treatment with disease-modifying antirheumatic drugs. Because of their limited disease-modifying effects, glucocorticoids should be combined with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

    Article and Author Information

    • Acknowledgments: The authors thank H.H. Nuver-Zwart, rheumatologist, for patient inclusion and support and B.G. Ziedzes des Plantes, radiologist, for advice; E.M.J. Brouwers-Kuyper, radiologist, and D.M. Hofman, rheumatologist, for scoring the radiographs; the Deventer Hospital pharmacists for preparation, randomization, and distribution of the study medication; and A.W.J.M. Jacobs-van Bree for data management.

    • Grant Support: By the Dutch League against Rheumatism (Het Nationaal Reumafonds) (no. 541).

    • Requests for Single Reprints: Johannes W.G. Jacobs, MD, Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, F02.127, Box 85500, 3508 GA Utrecht, the Netherlands; e-mail, j.w.g.jacobs{at}azu.nl.

    • Current Author Addresses: Dr. van Everdingen: Department of Rheumatology, Deventer Hospital, Box 5001, 7400 GC Deventer, the Netherlands.

    • Dr. Jacobs: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, F02.127, Box 85500, 3508 GA Utrecht, the Netherlands.

    • Dr. Siewertsz van Reesema: Department of Rheumatology, Deventer Hospital, Box 5001, 7400 GC Deventer, the Netherlands.

    • Dr. Bijlsma: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, F02.127, Box 85500, 3508 GA Utrecht, the Netherlands.

    • Author Contributions: Conception and design: A.A. van Everdingen, J.W.G. Jacobs, D.R. Siewertsz van Reesema, J.W.J. Bijlsma.

    • Analysis and interpretation of the data: A.A. van Everdingen, J.W.G. Jacobs, D.R. Siewertsz van Reesema, J.W.J. Bijlsma.

    • Drafting of the article: A.A. van Everdingen, J.W.G. Jacobs, D.R. Siewertsz van Reesema.

    • Critical revision of the article for important intellectual content: A.A. van Everdingen, J.W.G. Jacobs, D.R. Siewertsz van Reesema, J.W.J. Bijlsma.

    • Final approval of the article: A.A. van Everdingen, J.W.G. Jacobs, D.R. Siewertsz van Reesema, J.W.J. Bijlsma.

    • Provision of study materials or patients: A.A. van Everdingen, J.W.G. Jacobs.

    • Statistical expertise: A.A. van Everdingen, J.W.G. Jacobs.

    • Obtaining of funding: A.A. van Everdingen, J.W.J. Bijlsma.

    • Administrative, technical, or logistic support: A.A. van Everdingen, J.W.G. Jacobs, J.W.J. Bijlsma.

    • Collection and assembly of data: A.A. van Everdingen, J.W.G. Jacobs.

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    1. Ann Intern Med January 1, 2002 vol. 136 no. 1 1-12
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