Increased cortisol relative to adrenocorticotropic hormone predicts improvement during anti–tumor necrosis factor therapy in rheumatoid arthritis

Abstract

Objective. Some patients with chronic inflammatory diseases such as rheumatoid arthritis (RA) improve rapidly from anti-tumor necrosis factor (anti-TNF) therapy. No sensitive markers are available that might predict outcome of anti-TNF therapy. We undertook this study to investigate the predictive value of hypothalamic-pituitary-adrenal (HPA) axis hormones for clinical improvement during anti-TNF therapy.Methods. An observational study in 23 RA patients was followed by a validation study in 38 RA patients. The patients receiving anti-TNF antibodies had no glucocorticoid treatment, and we measured baseline serum levels of adrenocorticotropic hormone (ACTH) and cortisol. Improvement during anti-TNF antibody treatment was judged by the Disease Activity Score in 28 joints (DAS28), and serum levels of cortisol were measured at followup.Results. The observational study demonstrated that improvement in the DAS28 correlated negatively with baseline serum levels of cortisol (R ‫؍‬ ؊0.520, P ‫؍‬ 0.011) and the cortisol:ACTH ratio (R ‫؍‬ ؊0.700, P ‫؍‬ 0.0002). In the longitudinal part of the study at followup, those patients with good improvement and initially low serum levels of cortisol demonstrated an increase of serum cortisol, in contrast to patients with little or no improvement. Findings in the observational study were supported by those in the validation study in a group of RA patients with less inflammation (correlation of improvement in the DAS28 with cortisol:ACTH ratio: R ‫؍‬ -0.320, P ‫؍‬ 0.025).Conclusion. This is the first study in a human ISRCTN 68762628. FDA: BL 125057 (adalimumab portion of the studies).This publication reflects only the authors' views. The European Community is not liable for any use that may be made of the information herein.

Functional disturbance of the stress-adaptation system in patients with scleroderma

“…However, the cortisol levels did not increase after stress in SSc patients, and only the controls showed a response (increased cortisol level immediately after stress loading), thus suggesting a reduced adrenocortical response upon new stress in SSc patients. Similar findings have been reported for RA, which show the blunting of the responsiveness of the HPA axis to various stimuli such as surgical stress [10] and inflammatory stimulus [9][10][11][12][13][14][15][42][43][44][45].…”

Multiple Sclerosis

“…In contrast to studies in MS, the HPA axis in RA appears to be relatively blunted. Corticotropin and cortisol levels are generally reported as normal, suppressed, or inappropriately normal (lower than expected given circulating cytokine levels) (Straub et al, 2008). RA is associated with increased production of TNF-, and treatment with anti-TNF monoclonal antibodies is a key therapeutic option for RA.…”

The Pathogenetic Link Between Stress and Rheumatic Diseases

“…The HPA axis has been evaluated in multiple forms in former studies of RA patients. Assuming that an inflammatory process up-regulates HPA axis function, cortisol levels are inappropriately normal in RA patients when cytokine levels are increased (Straub et al, 2008). The proposed defect could reside at various levels of the HPA axis, i.e.…”

“…Psychological stress can influence immunoregulatory circuits and the course of an inflammatory disease (Marshall GD Jr, 1997). Furthermore, cytokines generated by the immune system influence hormonal secretion and the central nervous system, producing specific behavioural changes accompanying infectious and inflammatory diseases (Straub et al, 2008). Psychological distress and immune dysregulation have been linked to each other in chronic stress, in disease and other major life events.…”