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

Rainer H. Straub, Georg Pongratz, Maurizio Cutolo, Carla A. Wijbrandts, Dominique Baeten, Martin Fleck, Fabiola Atzeni, Mathias Grunke, Joachim R. Kalden, Jürgen Schölmerich, Hanns Martin Lorenz, Paul P. Tak, Piercarlo Sarzi-Puttini

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish
Pages (from-to)976-984
Number of pages9
JournalArthritis and Rheumatism
Volume58
Issue number4
DOIs
Publication statusPublished - Apr 2008

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Adrenocorticotropic Hormone
Hydrocortisone
Rheumatoid Arthritis
Tumor Necrosis Factor-alpha
Observational Studies
Serum
Joints
Validation Studies
Inflammation
Therapeutics
Chronic Disease
Antibodies
Glucocorticoids
Longitudinal Studies
Hormones

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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Increased cortisol relative to adrenocorticotropic hormone predicts improvement during anti-tumor necrosis factor therapy in rheumatoid arthritis. / Straub, Rainer H.; Pongratz, Georg; Cutolo, Maurizio; Wijbrandts, Carla A.; Baeten, Dominique; Fleck, Martin; Atzeni, Fabiola; Grunke, Mathias; Kalden, Joachim R.; Schölmerich, Jürgen; Lorenz, Hanns Martin; Tak, Paul P.; Sarzi-Puttini, Piercarlo.

In: Arthritis and Rheumatism, Vol. 58, No. 4, 04.2008, p. 976-984.

Research output: Contribution to journalArticle

Straub, RH, Pongratz, G, Cutolo, M, Wijbrandts, CA, Baeten, D, Fleck, M, Atzeni, F, Grunke, M, Kalden, JR, Schölmerich, J, Lorenz, HM, Tak, PP & Sarzi-Puttini, P 2008, 'Increased cortisol relative to adrenocorticotropic hormone predicts improvement during anti-tumor necrosis factor therapy in rheumatoid arthritis', Arthritis and Rheumatism, vol. 58, no. 4, pp. 976-984. https://doi.org/10.1002/art.23385
Straub, Rainer H. ; Pongratz, Georg ; Cutolo, Maurizio ; Wijbrandts, Carla A. ; Baeten, Dominique ; Fleck, Martin ; Atzeni, Fabiola ; Grunke, Mathias ; Kalden, Joachim R. ; Schölmerich, Jürgen ; Lorenz, Hanns Martin ; Tak, Paul P. ; Sarzi-Puttini, Piercarlo. / Increased cortisol relative to adrenocorticotropic hormone predicts improvement during anti-tumor necrosis factor therapy in rheumatoid arthritis. In: Arthritis and Rheumatism. 2008 ; Vol. 58, No. 4. pp. 976-984.
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AU - Atzeni, Fabiola

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N2 - 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 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.

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