AB0103 Polymyalgia rheumatica has a nocturnal rise in plasma interleukin-6 which is almost completely suppressed by night time administration of modified-release prednisone

Abstract

Background Musculoskeletal stiffness in polymyalgia rheumatica (PMR) follows a circadian rhythm. In rheumatoid arthritis (RA) patients, a timed release tablet of prednisone taken at 10pm led to a significant decrease in morning stiffness which was correlated with decreased night time plasma IL-6 [1]. However, the effects of timed release glucocorticoids on morning stiffness and the circadian profile of IL-6 in PMR have not been investigated. Previous studies of cytokines in PMR only collected blood samples at one time point mainly in the morning, without specifying the exact timing [2]. Objectives To determine whether IL-6 follows a circadian rhythm in patients with newly diagnosed untreated PMR, and to compare the effects of morning and night time glucocorticoids on overnight IL-6 and morning stiffness. Methods 10 patients with newly diagnosed PMR were randomised to two treatment groups with either night time modified-release prednisone 7mg (Lodotra) or morning immediate-release prednisolone 7mg. Hourly blood samples over 24-hours were taken before (Night A) and after 2 weeks treatment (Night B) to measure plasma IL-6. Patients were then treated with morning prednisolone 15mg and after 2 weeks a single measurement of IL-6 was performed at 9am (Day C). Duration of morning stiffness was recorded on each occasion. IL-6 assays were performed in Germany using the MILLIPLEX MAP kit. Results IL-6 showed a marked circadian variation in PMR, with a rise during the early hours of the morning which was partially suppressed by 7mg morning prednisolone and almost completely suppressed by 7mg night time prednisone (Figure 1a and 1b). Night time prednisone reduced morning stiffness by 90% compared to 42% with the morning prednisolone (p=0.044, t-test, figure 1c). Conclusions PMR, like RA, has a marked circadian variation in plasma IL-6. Both IL-6 and symptoms of morning stiffness are suppressed more by night time low dose glucocorticoids. This observation raises the possibility that PMR may be controlled by lower doses of glucocorticoids given at night compared to current conventional morning treatment. References Buttgereit, F., et al., Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in RA (CAPRA-1): a double-blind, randomised controlled trial. Lancet, 2008. 371(9608): p. 205-214. Spies, C.M., et al., More Night Than Day - Circadian Rhythms in Polymyalgia Rheumatica and Ankylosing Spondylitis. Journal of Rheumatology, 2010. 37(5): p. 894-899. Disclosure of Interest None Declared

Polymyalgia Rheumatica (PMR) Special Interest Group at OMERACT 11: Outcomes of Importance for Patients with PMR

“…Potential new opportunities to improve the treatment of PMR 16 make the definition of appropriate outcome measures a pressing need. From an industry perspective, outcomes used to support labeling claims need to meet the criteria laid down by regulatory bodies such as the US Food and Drug Administration 17 .…”

Our approach to the diagnosis and treatment of polymyalgia rheumatica and giant cell (temporal) arteritis

“…There is also a need to make a formal assessment of the relative risk of blindness due to deferring glucocorticoids until after TAB vs the side-effects of high-dose glucocorticoids in patients who do not have GCA. However, promising treatment breakthroughs such as the use of glucocorticoid chronotherapy in PMR 69 and anti-IL6 therapy in GCA [70][71][72][73] raise the possibility that we will be able to control these conditions on much lower doses of glucocorticoids and thus minimise the side-effect burden.…”