Individual Cortisol Production in Active Rheumatoid Arthritis Associates with Treatment Responses: A Pilot, Two-Year Study.

Introduction: Inadequate production of cortisol in relation to increased demands of chronic inflammation, a phenomenon coined as the "disproportion-principle", occurs in some patients with active rheumatoid arthritis (RA). Moreover, relatively lower diurnal cortisol production prior to antirheumatic treatment initiation/escalation for active RA has been associated with inadequate corresponding treatment responses after 6-months. Objective: To evaluate whether individual levels of endogenous cortisol in active RA patients followed in an Academic Rheumatology Unit may predict the type of response to subsequent antirheumatic treatment regimens after two years. Methods: We measured morning circulating ACTH, cortisol and DHEAS blood levels, as well as saliva diurnal-cortisol levels (collected samples at 08:00, 12:00, 18:00, 22:00), prior to treatment initiation/escalation in RA patients with active disease. In a pilot study, we prospectively examined for possible associations between these measurements and treatment responses at two years in those 24 patients who were under optimal management according to standard protocols. Results: The ratio of circulating cortisol/ACTH, as well as diurnal cortisol production at baseline were significantly lower in patients with moderate response or no response to treatment (7/24, 29%), than in those having disease remission at two-years (17/24, 71 %). Baseline diurnal-cortisol-production greater than 81.3 (calculated as area-under-the-curve) could predict remission at 24 months with 86% specificity and 65% sensitivity, independently of age, sex and baseline CRP levels (p=0.03). Conclusions: Further studies to confirm that lower diurnal cortisol production prior to treatment initiation/escalation in patients with active RA may predict inadequate corresponding responses in the long-term, are warranted.