Circadian Clock Modulation and Chronotherapy in Rheumatoid Arthritis: Molecular Mechanisms and Clinical Perspectives

Circadian rhythms determine biological clocks that manage daily biological functions, including the sleep–wake rhythm, hormone release, and immune function. This can affect immune-mediated chronic inflammation in rheumatoid arthritis (RA), which leads to joint damage, pain, swelling, and morning stiffness. These clinical manifestations follow a distinct circadian rhythm because of the cyclic pattern of leukocyte movement, secretion of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α at night, and fluctuations in cortisol and melatonin levels. Despite the increasing amount of evidence showing that insufficient sleep and disruption of the biological clock may play a role in RA development through suppression of the immune response in macrophages and resorption processes in osteoclasts, the cause of this phenomenon is still under investigation. The present-day guidelines continue to endorse DMARDs as the basis of treatment, while studies are exploring the role of chronotherapy as an adjunctive method for alleviating symptoms and enhancing disease outcomes. In this review, we explore current knowledge regarding the links between the molecular basis of circadian biology and the pathogenesis of RA, highlight recent trends in immune and bone remodeling mechanisms, and discuss modern possibilities for using chronotherapy, precision medicine, and advanced drug-delivery methods based on circadian rhythms to create optimal treatment strategies for RA.