**Part 1**

**DMARDs (Disease Modifying Anti-Rheumatic Drugs) and NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)** 

**1** 

 *UK* 

**The Clinical Role of Glucocorticoids in the** 

In 1949 Hench & Kendall published the first report of a treatment that was to revolutionise the management of rheumatoid arthritis (RA) (Hench & Kendall, 1949) and indeed, much of medicine. Their work was based on the observation that RA seemed to improve in patients who were pregnant or jaundiced. The adrenal cortex extract they used contained the hormone 17-hydroxy-11-dehydrocorticosterone, and they set the scene for the use of glucocorticoid (GC) therapy in the management of RA. In the 62 years since that seminal publication, our knowledge of the mechanisms of action of GC has increased markedly. The extent of GC use has ebbed and flowed because of concerns about adverse effects and in the light of the subsequent discovery of new anti rheumatic agents, but nevertheless the role of GC in the clinic has endured and around 10 million new prescriptions for oral GC are

In recent years the importance of GC in preventing long term joint erosions has been confirmed (Kirwan et al., 1995). Today they are seen as an important "disease modifying" agent in their own right and are recommended by the UK National Institute for Health and Clinical Excellence (NICE) for the early treatment of rheumatoid arthritis (Rudolph, 2009). Moreover, they remain an effective clinical tool for achieving short term control of disease flares especially in high doses administered intravenously. Their use in intra-articular injections is also a mainstay for targeting disease flares in particular joints and thus GC continue to form an important part of the therapeutic armoury of rheumatological practice

The main clinical problem associated with the use of GC is the numerous adverse effects. The most serious of these include the development of glucose resistance or in some instances type 2 diabetes. Other important adverse effects include hypertension, osteoporosis, skin changes, sleep disturbance, weight gain and changes to body fat distribution (Schäcke et al., 2002). This wide spectrum of actions reflects the many

As our knowledge of the action of GC increases, we can begin to tackle the two key challenges that lie ahead. Firstly, how can the benefits of these drugs be utilised while minimising their many adverse effects. Secondly, is it possible to identify a distinct subset of patients with inflammatory disorders who are resistant to GC. Apart from RA, clinical GC resistance can be found in a range of inflammatory conditions including asthma, inflammatory bowel disease and uveitis (Barnes & Adcock, 2009). GC-resistant disease is the

written each year in the USA alone (Schäcke et al, 2002)

**1. Introduction** 

(van Vollenhoven, 2009).

physiological roles of endogenous GC.

**Management of Rheumatoid Arthritis** 

*Academic Rheumatology Unit, Bristol Royal Infirmary, Bristol* 

Hussein Al-Mossawi and John R. Kirwan
