title: 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).
  
  
  CONCLUSIONS
  This is the first study in a human chronic inflammatory disease to demonstrate that inflammation-induced TNF interferes with HPA axis integrity, which is linked to the disease outcome. These findings position the HPA axis centrally in the vicious circle of perpetuation of chronic inflammation.
authors.affiliation: Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany. rainer.straub@klinik.uni-regensburg.de
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
authors.forename: Georg
authors.initials: G
authors.lastname: Pongratz
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
authors.forename: Carla A
authors.initials: CA
authors.lastname: Wijbrandts
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
authors.forename: Martin
authors.initials: M
authors.lastname: Fleck
authors.forename: Fabiola
authors.initials: F
authors.lastname: Atzeni
authors.forename: Mathias
authors.initials: M
authors.lastname: Grunke
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Kalden
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schölmerich
authors.forename: Hanns-Martin
authors.initials: HM
authors.lastname: Lorenz
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Sarzi-Puttini
mesh_terms: D000068879:Adalimumab; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D000069285:Infliximab; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000276:immunology; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D000324:Adrenocorticotropic Hormone; D000069285:Infliximab; D000068879:Adalimumab; D006854:Hydrocortisone