Accumulating observations of women with rheumatoid arthritis (RA) who ‘spontaneously’ experienced less active disease during pregnancy led to the growing belief by Philip Hench that a hormonal substance had to be involved in the improving clinical conditions of pregnant patients with RA. In close collaboration with Edward Kendall and Tadeus Reichstein they eventually managed to isolate, identify and produce compound E (i.e. cortison) and administered the compound to RA patients with impressive results. Ever since, glucocorticosteroids (GC) are being used in a variety of inflammatory and noninflammatory disorders because of their powerful anti-inflammatory and immunomodulating properties. As such, GC are also frequently used in early and longstanding RA, although long-term use of GC is also associated with dose- and time-dependent side effects such as changes in body composition (obesity, muscle atrophy, osteoporosis), diabetes and hypertension. However, large interindividual differences in GC sensitivity are present, reflected by different treatment responses and by the degree to which side effects develop. In addition, abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis itself have been recognized in RA which may contribute to its pathogenesis. This justifies the search for determinants of GC sensitivity, in order to individualize and optimize GC therapy in RA, and to further unravel HPA-axis dysfunction in the pathophysiology of RA.

Financial support for the publication of this thesis was kindly provided by: Dutch Arthritis Foundation, Merck Sharp & Dohme B.V., Goodlife Healthcare, Pfizer B.V., Daiichi Sankyo B.V.
J.M.W. Hazes (Mieke) , S.W.J. Lamberts (Steven)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam