Efficacy, safety and mechanism of action of modified-release prednisone in rheumatoid arthritis.

Glucocorticoids (GCs) provide a powerful and widely used anti-inflammatory and disease-modifying therapy for rheumatoid arthritis (RA). However, concerns about adverse effects are driving efforts to find 'safer' GC or GC analogues. One novel approach has been to change the timing of GC delivery, targeting the early hours of the morning to suppress the observed circadian peak in interleukin-6 (IL-6). The CAPRA-1 study has shown that this produces a clinically useful beneficial improvement in morning stiffness and mechanistic studies have shown that this correlates with a strong suppression of the IL-6 early morning peak. With no obvious additional adverse reactions, this improvement in the therapeutic ratio offers additional treatment options in RA, and perhaps in other inflammatory diseases that show circadian variation in symptoms.