The 70th Anniversary of Glucocorticoids in Rheumatic Diseases

The Second Youth of an Old Friend

Yannick Palmowski; Thomas Buttgereit; Frank Buttgereit

Disclosures

Rheumatology. 2019;58(4):580-587. 

In This Article

Abstract and Introduction

Abstract

Seventy years ago, the first administration of cortisone in a patient with RA marked a milestone in the treatment of inflammatory diseases. However, the initial enthusiasm rapidly vanished as the administration of high doses for lengthy periods revealed worrisome adverse effects. It has taken several decades to overcome the (sometimes excessive) mistrust and to achieve a more differentiated evaluation of the benefit–risk profile and the adequate usage of glucocorticoids (GCs). Today, GCs remain indispensable for the treatment of many inflammatory conditions and their usefulness in RA as a disease-modifying low-dose co-medication is widely acknowledged. Recent studies show promising results concerning both traditional GCs and new formulations. Still, decades of relatively little scientific attention have resulted in a continuing lack of detailed evidence. Hence there is an ongoing need for further research regarding mechanisms of GC actions, the further optimization of treatment parameters for traditional GCs and new formulations.

Introduction

On 21 September 1948, the first administration of cortisone in a patient with RA marked a breakthrough in the pharmacological treatment of rheumatologic diseases. Seventy years later, glucocorticoids (GCs) can now look back onto an eventful and turbulent past. After several years as an enthusiastically acclaimed miracle drug, the observation of unacceptable adverse effects under extensive use led to (sometimes excessively) high caution and vanishing scientific interest. Still, GCs never disappeared from the armamentarium of drugs used in rheumatology thanks to their undoubted anti-inflammatory and immunosuppressive effectiveness. In many conditions, including various forms of vasculitis, inflammatory myopathies and several non-rheumatic diseases, they have remained an important therapy element since their introduction. In RA, they spent decades as 'a treatment of last resort, at the top of the therapeutic pyramid'[1] but have rather recently experienced a resurgence as a low-dose co-medication as evidence about their disease-modifying potential at low dosages is accumulating.[2] At the same time, their possible adverse effects have become both better understood and, at least in part, preventable or treatable, with modern anti-osteoporotic medications like bisphosphonates being one example. Yet, the long period GCs have spent close to scientific oblivion has surely left its mark.

Due to the paucity of research for such a long time, even after decades of clinical use we have still not gathered sufficient evidence to allow for comprehensive and scientifically fully backed treatment recommendations or to decide upon their definite role in the treatment of RA and other rheumatic diseases.[3] Quite the contrary, 70 years after their introduction the role of GCs remains an issue of ongoing controversy, leading to fierce debates between supporters and opponents of more widespread use.[4,5]

The assessment of traditional GCs is not the only aspect concerning GCs that keeps evolving. New formulations like modified-release prednisone, liposomal GCs or selective GC receptor agonists are the topic of current research or have already found their way into clinical medicine. After several decades of hibernation, one could say that GCs are currently experiencing a second youth.

In this review we will briefly recapitulate the history of GCs, summarize the current situation and give an overview of recent and ongoing research.

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