ANTI-TNF ANTIBODY THERAPY DOES NOT CHANGE SERUM LEVELS OF CORTISOL BINDING GLOBULIN IN PATIENTS WITH RHEUMATOID ARTHRITIS BUT IT INCREASED ANDROSTENEDIONE RELATIVE TO CORTISOL

Background: In a chronic inflammatory disease such as rheumatoid arthritis (RA), the hypothalamic-pituitary-adrenal (HPA) axis demonstrates alterations. Causes for these alterations are only partly understood but cytokines such as IL-6 and TNF are likely to play a prominent role for these alterations.Cortisol binding globulin (CBG) is produced by liver cells and is inhibited by proinflammatory cytokines such as IL-6. CBG serum levels are typical low during prolonged inflammatory processes. Thus, observed changes of cortisol during anti-TNF therapy may be related to changes of CBG in RA.Objectives: This study was aimed at investigating the course of CBG during anti-TNF therapy in RA.Methods: In this longitudinal study with subcutaneous adalimumab we included 13 RA patients without prior prednisolone. All patients were clinically investigated and blood was drawn between 08:00 and 09:00 in the morning when the patients visited the outpatient clinic on the baseline day, week 2, 6, and 12. The blood was immediately centrifuged and serum was stored on – 80°C. We used radioimmunometric assays for the quantitative determination of serum levels of CBG and cortisol. Serum levels of IL 6, androstenedione, and ACTH were measured by immunometric enzyme immunoassays.Results: Upon treatment with anti-TNF, we observed a strong decrease of clinical markers of inflammation and serum IL-6. Serum levels of cortisol remained relatively stable (615.3± 81.5 vs. 569.6± 77.1 nmol/l), CBG, and the cortisol/CBG ratio did not markedly change, whereas the CBG/IL-6 increased (p=0.004). In parallel, levels of ACTH decreased during 12 weeks of anti-TNF therapy (baseline vs. 12 weeks: 1.6± 0.1 vs. 1.2± 0.1 pmol/l, p=0.007). The ratio of the adrenal androgen androstenedione divided by serum cortisol increased during the observation period (p=0.036).Conclusion: This study demonstrates relatively normal levels of CBG and a normal ratio of CBG/cortisol during anti-TNF therapy. Thus, earlier observed changes of cortisol in relation to IL-6 during anti-TNF therapy may not be related to changes of CBG. This study further confirmed some of our earlier data with infliximab in another cohort.Citation: Ann Rheum Dis, volume 64, supplement III, year 2005, page 443Session: Rheumatoid Arthritis – Treatment