Chronotherapy with modified-release prednisone in patients with rheumatoid arthritis

Abstract

Glucocorticoids are indispensable for the treatment of systemic inflammatory diseases such as rheumatoid arthritis (RA), though their beneficial effects have to be balanced with potential complications arising from high doses, prolonged use or dose splitting. A glucocorticoid formulation (modified-release prednisone) has been developed to be taken in accordance with biological rhythms (chronotherapy). Morning symptoms of RA are caused by elevated nocturnal levels of proinflammatory cytokines, particularly IL-6. Endogenous cortisol levels may be insufficient to counter the inflammatory effects of IL-6. The early morning rise in cortisol can be supplemented with exogenous glucocorticoid replacement therapy if this is given as the recently developed chronotherapy formulation. There is no adverse impact of modified-release prednisone on the hypothalamic-pituitary-adrenal (HPA) axis; indeed, there might be evidence of a beneficial effect on HPA axis function. This review summarizes the development of modified-release prednisone, pharmacokinetic characteristics and clinical experience in patients with RA.

Role of LncRNA-AF085935, IL-10 and IL-17 in Rheumatoid Arthritis Patients With Chronic Hepatitis C

“…This higher serum IL-17 in patients with chronic liver disease goes with what has been reported previously that serum IL-17 level was increased in liver injuries following chronic hepatitis and cirrhosis supporting a role for IL-17 as a chronic disease inducer in the pathogenesis and/or progression of liver fibrosis [34]. Administration of corticosteroid therapy is associated with a decrease in inflammatory markers levels due to its anti-inflammatory effects [63]. Our results detected that the high expression of lncRNA-AF085935 in our patients of RA associated with HCV is highly significant than in healthy individuals who show underexpression of this lncRNA.…”

Benefits and risks of low-dose glucocorticoid treatment in the patient with rheumatoid arthritis

“…RA symptoms have a circadian rhythm with the greatest severity in the early morning. A number of hypotheses have been put forward to explain this, including redistribution of interstitial fluids, circadian changes in synovial fluid composition and resultant oedema of the synovium and the peri-articular structures that interfere with joint biomechanics and nocturnal elevation in inflammatory mediators such as IL-6 that are not counterbalanced by a concomitant increase in cortisol [67, 68]. Increased production of melatonin at night may also contribute to the circadian pattern of clinical symptoms of RA [69].…”

Involvement of the Circadian Rhythm and Inflammatory Cytokines in the Pathogenesis of Rheumatoid Arthritis

“…Interestingly, it has been shown that T cell numbers and its reactivity were stable during daytime, whereas a significant increase was observed in the late evening and early morning hours ex vivo [35]. These results may explain the portion of etiology for “morning stiffness of joints,” a common complaint and one of the best indicators of the condition of RA patients, correlates with the secretion of TNF- α , IL-6, and IFN- γ , whose levels peak from midnight to early in the morning [36], and chronobiology-based approach has been tested and shown to improve the morning symptoms of RA [37, 38]. …”