Optimising glucocorticoid therapy in rheumatic diseases : an incompatible triangle?

Abstract

As this thesis discusses, an incompatible situation arises when toxicity predominates over efficacy particularly in case high cumulative doses of GCs have been used. This has stigmatised their usage, which is often unwarranted when GC therapy is applied with sufficient precautionary measures (safety). The most obvious example is osteoporosis prophylaxis in patients on long-term GC therapy. When the three dimensions or axes related to the use of GCs namely efficacy, toxicity and safety of GC therapy are balanced, a good benefit-risk ratio and harmonious situation exist: a compatible triangle. The main message from the first axis or theme ‘efficacy’ is that low-to-medium dose systemic GCs indeed deserve to be part of modern treat-to-target or tight control RA treatment strategies, as GCs are DMARDs and clearly improve the prognosis of RA patients. Whether the DMARD-effect of GC co-therapy persists after 2 years of treatment remains yet to be investigated, and also whether the triangle of dimensions stays compatible during chronic GC-treatment for this purpose. The second theme ‘toxicity’ points out that patients on chronic GC-treatment still suffer from a high incidence of vertebral fractures; also disturbed glucose metabolism was detected in a substantial number of RA patients with established disease, both in those on GC therapy and those without GCs. With regards to these 2 co-morbidities, it is still not clear what the direct effects of GCs are, and what the effects of disease activity. More research on the basic mechanisms of GC-related osteoporosis and glucose intolerance, especially in randomised placebo-controlled GC studies with frequent longitudinal assessments is needed, also in patients chronically treated with GCs. The results of such investigations could suggest potential mechanisms for new (prophylactic) therapies, aimed at e.g. specific adipocytokines and bone regulating cytokines, through which the triangle of GC-use would become more compatible. Significant focus of future studies on long-term GC-use should be on other, e.g. cardiovascular AEs. Safety is the third theme of GC-use and of crucial importance for the compatibility of the triangle of GC-use; associated with both efficacy and toxicity. Based on a review of GC-associated AEs, a broad set of recommendations has been formulated to prevent or treat these AEs during treatment. This enables safer long-term use of GCs and enhances the compatibility of the GC-use triangle. However, for interpretation of AEs, the direct effects of GCs and the effects of disease activity proved to be difficult to unravel; most recommendations are not fully evidence-based by lack of data.