RESEARCH - Targeting pathophysiological rhythms: prednisone chronotherapy shows sustained efficacy in RA

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Ann Rheum Dis 2010;69:1275-1280 doi:10.1136/ard.2009.126888

Clinical and epidemiological research

Extended report

Targeting pathophysiological rhythms: prednisone chronotherapy shows

sustained efficacy in rheumatoid arthritis

Buttgereit1, Gisela Doering2, Achim Schaeffler3, Stephan Witte3,

Stanislaw Sierakowski4, Gromnica-Ihle5, Slawomir Jeka6, Klaus

Krueger7, Jacek Szechinski8, Rieke Alten9

+ Author Affiliations

1Department of Rheumatology and Clinical Immunology, Charité

University Medicine, Berlin, Germany

2Merck KGaA, Darmstadt, Germany

3Nitec Pharma GmbH, Mannheim, Germany

4Department of Rheumatology, Medical University, Bialystok, Poland

5Immanuel Krankenhaus, Berlin-Buch, Germany

6Clinical Trials Office, Torun, Poland

7Praxiszentrum St Bonifatius, München, Germany

8Katedra i Klinika Reumatologii i Chorob Wewnetrznych AM, Wroclaw, Poland

9Department of Internal Medicine, Rheumatology, Charité Teaching

Hospital – Schlosspark-Klinik, Berlin, Germany

Accepted 6 May 2010

Published Online First 11 June 2010

Abstract

Objective This 9-month open-label extension of the Circadian

Administration of Prednisone in Rheumatoid Arthritis Study (CAPRA 1)

investigated the long-term safety and efficacy of prednisone

chronotherapy with a novel modified-release (MR) prednisone for up to

12 months.

Methods Of 288 patients with rheumatoid arthritis originally

randomised to MR or immediate-release (IR) prednisone, 249 continued

with prednisone chronotherapy (2–10 mg/day) in the 9-month open-label

extension. Duration of morning stiffness of the joints (MS), disease

activity scores (DAS28), American College of Rheumatology (ACR20)

responses and plasma levels of interleukin 6 (IL-6) were assessed.

Safety was analysed from adverse event reports and laboratory

investigations.

Results During the 3-month double-blind phase, patients in the MR

group achieved a reduction in MS of 33.1% while no change was observed

in the IR group. After 6 months of treatment, MS was reduced in the

IR/MR group by 54% and in the MR/MR group by 56%. MS reduction after

12 months was 45% (IR/MR group) and 55% (MR/MR group). Plasma levels

of IL-6 declined on MR treatment. DAS28 was reduced from 5.8 to 4.8

(MR/MR group) and 4.9 (IR/MR group), respectively. 37% of the 219

patients who completed the 12-month study achieved improvement

according to the ACR20 criteria. Adverse events did not differ from

the known profile of low-dose prednisone.

Conclusions Prednisone chronotherapy with the MR tablet was safe and

well tolerated and provided a sustained improvement which resulted in

a better benefit to risk ratio of low-dose glucocorticoid treatment

for at least 12 months.

http://ard.bmj.com/content/69/7/1275.abstract

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