ADVERSE EFFECTS OF GLUCOCORTICOIDS: OVER- OR UNDERESTIMATED? INTRODUCTION OF MONITORING GUIDELINES

J.W.J. Bijlsma, J.W.G. Jacobs , J.A.P. Da Silva Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands, Reumatologia, Hospitais da Universidade de Coimbra, Coimbra, PortugalGlucocorticoids play a pivotal role in the management of rheumatic diseases. The proportion of patients treated with glucocorticoids by practicing physicians on a daily basis is clearly in excess of the usual recommendations in textbooks. Recent studies demonstrating disease modifying potential of low-dose glucocorticoids in rheumatoid arthritis have renewed the debate on risk/benefit ratios with this therapy.This lecture deals with the assessment of the risks of glucocorticoids and how to monitor these. To really evaluate this risk we should consider at least two different components:A. what is the real incidence of adverse effects, using different dosages, with focus on low dosages (7.5 mg prednisone daily or less)?B. what is the rating of these adverse effects in terms of severity by the physicians and also by the patients?Perhaps in the future this may lead to a so called toxicity index for glucocorticoids.Ad A. to address the problem of the real incidence of adverse effects a meeting was held in Portugal, Coimbra, of experts (rheumatologists and endocrinologist) with a special interest in this area, from Europe and the USA, including representation of groups that have conducted both epidemiologic and randomized controlled clinical trials on the use of glucocorticoids in rheumatoid arthritis. A careful review of the literature was performed and the data of 5 large prospective placebo controlled studies with a low dosage of glucocorticoids during two years were evaluated. A report of this evaluation is in press (JAP Da Silva, Annals of the Rheumatic Diseases, 2004).The incidence of adverse effects in RA-patients, treated with low dosages of glucocorticoids, was much lower then expected from literature, e.g. development of diabetes mellitus was comparable in the glucocorticoid treated groups versus placebo treated grouips: 2/185 versus 3/186, while the development of hypertension was 19/281 patients in the glucocorticoid treated groups, versus 12/276 in the placebo treated groups.Ad B. How is the severity of the adverse effects rated by physicians and by patients? How do we compare the development of atrophy of the skin with congestive heart failure; and is the physician more concerned by osteoporosis and the patient more by easy bruising? Data on these aspects are paramount to give a fair judgement on toxicity, as one component of the risk/benefit ratio of this treatment, but these data are hardly available. Presently initiatives are being developed to come to a toxicity index, based on the two questions above.Based on the present knowledge, partly biased by an abundance of literature on the "well known" side effects, partly influenced by the (incomplete) evidence from prospective, placebo controlled trials, we propose that the following adverse effects need to be monitored, and that preventive measures should be taken when indicated, such as for osteoporosis.– Osteoporosis hypertension– Cataracts and glaucoma– Peptic ulcer (if comedication with NSAIDs)– New-onset diabetes mellitus (DM) in subjects at risk for developing DM– Worsening of glycemic control in patients with DM– Cushingoid symptoms– Growth retardation in children– Adrenal crisis on glucocorticoid withdrawalReferences: 1. Da Silva JAP, Jacobs JWG, Ines LBS, Saag KG, de Koning EJP, Buttgereit F, Cutolo M, Capell H, Rau R, Kirwan JR, Boers M, Bijlsma JWJ. Long-term glucocorticoid therapy in rheumatoid arthritis: an evidence-based review of potential adverse effects. Ann Rheum Dis, in press 2004.2. Buttgereit F, Da Silva JAP, Boers M, Burmeister GR, Cutolo M, Jacobs JWG et al. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis 2002; 61: 718-22.3. Bijlsma JWJ, Boers M, Saag KG, Furst DE. Glucocorticoids in the treatment of early and late RA. Ann Rheum Dis 2003; 62: 1033-7.Citation: , volume , supplement , year 2004, page Session: Glucocorticoids update 2004