Clinical Features and Treatment of Rheumatoid Arthritis: A Review

Abstract

It is evident that the morning symptoms of rheumatoid arthritis (RA) are linked to the circadian abnormal increase in night inflammation, favoured by inadequatecortical secretion under conditions of active disease. Therefore, exogenous glucocorticoids treatment is recommended in RA at low doses in cetimay partially act like a ‘replacement therapy’. The prevention/treatment of the night up regulation of the immune/ inflammatory reaction (and related flare of cytokine synthesis) has been shown to be more effective when exogenous glucocorticoids administration is obtained with a night time release formulation. Formulation large scale trials documented that modified-release prednisone has greater efficacy then morning prednisone for long term low dose glucocorticoids treatment in patients with RA, showing at least a more significant reduction in morning joint stiffness. Interestingly, despite a considerably higher cost than conventional prednisone, chronotherapy with night time release prednisone was recognised as a cost effective option for patients with RA not on glucocorticoids who are eligible for therapy with biological disease modifying antirheumatic drug (DMARDs). Moreover, since different cell populations involved in the inflammatory process are particularly activated during the night, other therapeutically approaches used in RA, for example, conventional DMARDs and non-steroidal anti-inflammatory drugs (NSAIDs), should follow the same concepts of glucocorticoids chronotherapy. Indeed, bedtime methotrexate chronotherapywas found to improve RA symptoms compared to the current standard dosing methods, and several available NSAIDs (i.e., indomethacin, aceclofenac, ketoprofen, flurbiporfen, lornoxicam) have been very recently modified in their formulation, in order to obtain chronotherapeutical effects inRA.