Targeting pathophysiological rhythms: prednisone chronotherapy shows sustained efficacy in rheumatoid arthritis.
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.
Buttgereit
Frank
F
Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany. frank.buttgereit@charite.de
Doering
Gisela
G
Schaeffler
Achim
A
Witte
Stephan
S
Sierakowski
Stanislaw
S
Gromnica-Ihle
Erika
E
Jeka
Slawomir
S
Krueger
Klaus
K
Szechinski
Jacek
J
Alten
Rieke
R
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
D018501:Antirheumatic Agents; D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D011241:Prednisone