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Low-dose Prednisolone in Rheumatoid Arthritis: Adverse Effects of Various Disease Modifying Antirheumatic Drugs

OLGA A. MALYSHEVA, MATTHIAS WAHLE, ULF WAGNER, MATTHIAS PIERER, SYBILLE ARNOLD, HOLM HÄNTZSCHEL, and CRISTOPH G.O. BAERWALD

ABSTRACT.

Objective.
To assess the incidence and severity of disease modifying antirheumatic drug (DMARD)-induced adverse effects (AE) in patients with rheumatoid arthritis (RA) taking/not taking glucocorticoids (GC). More specifically, we tested whether GC can prolong the survival time of DMARD in patients receiving combination therapy.

Methods. In a retrospective study of 154 patients with RA, data were examined for DMARD therapy and duration of low-dose GC (¾ 7.5 mg prednisone equivalent/day). Patients were followed for 2-62 months, and AE were graded following WHO criteria.

Results. GC therapy significantly increased the duration of therapy with sulfasalazine (SSZ) from 10.4 ± 2.3 to 22.5 ± 1.9 months and for methotrexate (MTX) from 21.8 ± 2.9 to 43.3 ± 2.7 months. Stratifying the withdrawal of DMARD for occurrence of AE and loss of efficacy revealed that GC comedication significantly increased the time until AE for users of MTX (3.0 ± 0.6 vs 18.8 ± 1.3 mo; p < 0.05), hydroxychloroquine (HCQ; 34.5 ± 4.6 vs 54.4 ± 5.1 mo; p < 0.05), and gold (6.6 ± 0.9 vs 10.5 ± 0.9 mo; p < 0.05). In patients taking SSZ the time until cessation due to loss of efficacy increased significantly under GC comedication (16.8 ± 1.2 vs 31.3 ± 2.9 mo; p < 0.05). However, in patients taking azathioprine (AZA) the duration of therapy decreased from 44.4 ± 2.6 to 22.3 ± 1.6 months under GC due to both time until AE and loss of efficacy. Patients under comedication of MTX GC, HCQ GC, and AZA GC experienced significantly more AE compared to the respective DMARD monotherapy. A highly significant reduction was observed in the frequency of erosive RA in patients with GC comedication (n = 30; 49.1%) compared to patients without low-dose GC (n = 81, 80.4%; OR 4.05, 95% CI 1.91-8.66, p < 0.0001).

Conclusion. Low-dose GC retard radiological progression of RA and exhibit a differential effect on survival of DMARD and degree of AE due to DMARD. Further studies are warranted to address safety and interactions of chronic low-dose GC in RA patients treated with DMARD. (J Rheumatol First Release April 15 2008)

Key Indexing Terms:

ADVERSE EFFECTS
LOW-DOSE GLUCOCORTICOIDS
RHEUMATOID ARTHRITIS
DISEASE MODIFYING ANTIRHEUMATIC DRUG


From the Medical Clinic and Polyclinic IV, University Hospital, Leipzig; and Klinikum der Johann W. Goethe-Universität Frankfurt, Medizinische Klinik II, Rheumatology, Frankfurt, Germany.

O.A. Malysheva, MD, Medical Clinic and Polyclinic IV, University Hospital, Leipzig; M. Wahle, MD, Klinikum der Johann W. Goethe-Universität Frankfurt; U. Wagner, MD, Professor; M. Pierer, MD; S. Arnold, MD; H. Häntzschel, MD, Professor; C.G.O. Baerwald, MD, Professor, Medical Clinic and Polyclinic IV, University Hospital, Leipzig.

Address reprint requests to Dr. O. Malysheva, Medical Clinic and Polyclinic IV, University Hospital, Liebigstrasse 22, 04103 Leipzig, Germany. E-mail: Olga.Malysheva@medizin.uni-leipzig.de

Accepted for publication January 24, 2008.



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