How should impaired morning function in rheumatoid arthritis be treated?

Abstract

Patients with rheumatoid arthritis (RA) commonly experience morning symptoms of joint stiffness and pain that result in impaired function. However, current treatment options are limited. The management of impaired morning function is based primarily on non-pharmacological approaches, including simple or short exercises, application of heat or a hot shower or bath, and delaying activities until later in the day. Although it seems that the majority of patients follow the management advice they are given by rheumatologists, symptoms persist. In recent years, only a minority of clinical studies have assessed the impact on morning symptoms of pharmacological treatments for RA. The paucity of data makes it difficult to evaluate systematically the ability of current treatments to improve morning function. However, treatment seems to be suboptimal; in a pan-European survey of 518 rheumatologists, 61% considered that current treatment options do not address impaired morning function specifically, and 68% considered there is a need for new treatment options. Understanding the pathophysiology of circadian symptoms may provide the key to improving treatment of impaired morning function. In patients with morning symptoms of RA, there may be insufficient endogenous cortisol released during the night to counter elevated levels of the pro-inflammatory cytokine, interleukin (IL)-6. Delivering exogenous glucocorticoid during the night was found to reduce IL-6 levels and reduce morning stiffness, but was inconvenient for patients. However, this chronotherapeutic approach has now been facilitated by the development of modified-release prednisone tablets. Taken at bedtime (approximately 10:00 pm), these tablets give programmed delivery of prednisone around 4 h later, at the optimal time to suppress IL-6. Clinical studies suggest that morning stiffness in patients with RA could be treated successfully with the use of low-dose modified-release prednisone.

The Use of patient Reported Outcome Measures for Rheumatoid Arthritis in Japan: A Systematic Literature Review

“…Research that differentiates treatment-induced versus disease-induced fatigue is warranted. Morning stiffness was recognized as an unmet treatment need as currently there are no pharmacological treatments that can ease the symptoms but it has been persistently reported by patients [45]. For morning stiffness, only 2 studies identified measuring the duration of morning stiffness.…”

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

“…Thus there is still an unmet need to allow ever more patients to achieve the highest levels of disease control [77]. There is substantial evidence that low-dose GC treatment, when combined with conventional DMARDs, can significantly slow disease progression and increase the number of patients who achieve disease remission.…”

Chronotherapy with modified-release prednisone in patients with rheumatoid arthritis

“…Furthermore, available treatment for morning symptoms of RA appears to be unsatisfactory [16]. In a survey of 518 European rheumatologists, 61% noted that current treatment options do not specifically address impaired morning function, with a similar proportion (68%) recognizing the need for a new treatment [17].…”