Low-dose glucocorticoid therapy in rheumatoid arthritis. A review on safety: published evidence and prospective trial data

José AP da Silva ^1*, Johannes W.G. Jacobs ², John R. Kirwan ³, Maarten Boers ⁴, Kenneth G. Saag ⁵, Luis B.S. Inês ⁶, Eelco J.P. de Koning ⁷, Frank Buttgereit ⁸, Maurizio Cutolo ⁹, Hilary Capell ¹⁰, Rolf Rau ¹¹ and Johannes W. J. Bijlsma ¹²

¹ Hospitais da Unversidade Coimbra, Portugal
² UMCU, Netherlands
³ University of Bristol, United Kingdom
⁴ VU University Medical Center. Amsterdam, Netherlands
⁵ University of Alabama at Birmingham, United States
⁶ Hospitais da Universidade de Coimbra, Portugal
⁷ Leiden University Medical Center, Netherlands
⁸ Charité Universitätsmedizin Berlin, Germany
⁹ Department of Internal Medicine, University of Genova, Italy
¹⁰ Royal Infirmary Glasgow, United Kingdom
¹¹ Evangelisches Fachkrankenhaus, Ratingen, Greece
¹² University Medical Center Utrecht, Netherlands

^* To whom correspondence should be addressed. E-mail: jdasilva{at}ci.uc.pt.

Accepted 25 July 2005

Abstract

Objective: To assess the incidence and severity of adverse-effects of long-term low-dose glucocorticoid therapy in rheumatoid arthritis.

Materials and methods: We reviewed the literature of clinical trials and physiological studies evaluating adverse effects of glucocorticoids. In addition, safety data from four prospective, randomised, placebo- controlled clinical trials of two years duration evaluating the effect of low-dose glucocorticoids (<10mg prednisone equivalent per day) in patients with mainly active, early rheumatoid arthritis was evaluated. Results from the COBRA trial, which used higher doses for a short period of time, followed by 5 months low dose, are also analysed.

Results: Adverse-effects of glucocorticoids are abundantly referred to in literature. However, in the available literature on low-dose glucocorticoid therapy very little of the commonly held beliefs about their incidence, prevalence and impact of GC proved to be supported by clear scientific evidence. Additional data from the randomised controlled clinical trials reviewed showed that the incidence, severity and impact of adverse effects of low dose glucocorticoid therapy in rheumatoid arthritis trials are modest, and often not statistically different to those of placebo.

Conclusions: Probably many of the well known adverse effects of glucocorticoids are predominantly associated with high dose treatment. Given the lack of sound evidence, the use of low-dose glucocorticoids in rheumatoid arthritis merits reconsideration, weighing the risks and benefits. Further studies designed to address safety of chronic low-dose glucocorticoid treatment in rheumatoid arthritis are warranted to establish the true incidence, severity and impact of adverse-effects.

Keywords: Adverse-effects, glucocorticoids, review

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