Can we shift the benefit-risk ratio of glucocorticoids?

Abstract

Glucocorticoids have a wide range of anti-inflammatory and immunomodulatory effects, but they also regulate processes within carbohydrate, protein, and fat metabolism. 1 Strehl C Ehlers L Gaber T Buttgereit F Glucocorticoids—all-rounders tackling the versatile players of the immune system. Front Immunol. 2019; 101744 Crossref PubMed Scopus (104) Google Scholar The excellent clinical efficacy of glucocorticoids—for example, in rheumatoid arthritis—is limited by the potential occurrence of unwanted adverse effects. 2 Luis M et al. An updated review of glucocorticoid-related adverse events in patients with rheumatoid arthritis. Expert Opin Drug Saf. 2019; 18: 581-590 Crossref PubMed Scopus (27) Google Scholar Therefore, early attempts were made to optimise their benefit–risk ratio by developing synthetic glucocorticoids such as prednisone or prednisolone. These synthetic analogues differ from endogenously produced glucocorticoids in that they have a substantially stronger anti-inflammatory but less undesirable mineralocorticoid effects. Further optimisations were achieved through the development of guidelines and recommendations on how to best use glucocorticoids in rheumatology. 3 Hellmich B et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2019; (published online July 3.)DOI:10.1136/annrheumdis-2019-215672 Crossref PubMed Scopus (401) Google Scholar , 4 Smolen JS et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017; 76: 960-977 Crossref PubMed Scopus (1800) Google Scholar Effects of a selective glucocorticoid receptor modulator (AZD9567) versus prednisolone in healthy volunteers: two phase 1, single-blind, randomised controlled trialsAZD9567 appears to be safe and well tolerated in healthy, predominantly white male volunteers and shows promising initial evidence for improved post-prandial glucose control. Studies of longer duration, with a greater proportion of women and other ethnic groups, and in patients requiring anti-inflammatory treatment are needed to characterise the clinical efficacy and safety profile of AZD9567. Full-Text PDF