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.

Acknowledgements

This paper is based on a presentation given by the author at a meeting held in Copenhagen, Denmark on 22 September 2010. The meeting was arranged and sponsored by Mundipharma International Limited; the author received travel expenses to attend the meeting and an honorarium for his contribution. The pan-European survey was conducted by Ipsos MORI and funded by Mundipharma International Limited. D Storey of DPS Limited assisted with the literature searches, prepared the first draft of the manuscript for the author's review, and provided editorial support. The author reports receiving consultancy fees, honoraria, and travel expenses from Merck Serono, Horizon Pharma (formerly Nitec Pharma), and Mundipharma International Limited, and grant support from Merck Serono and Horizon Pharma.