Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Low-Dose Glucocorticoid Chronotherapy of Rheumatoid Arthritis: 12 Week Efficacy and Safety of Modified-Release (MR) Prednisone.

Buttgereit2,  Frank, Mehta3,  Daksha P., Kirwan1,  John R., Szechinski7,  Jacek, Boers12,  Maarten, Alten10,  Rieke, Supronik8,  Jerzy

Bristol Royal Infirmary, Bristol, United Kingdom
Schlosspark-Klinik, UnivMed, Berlin, Germany
University of Alabama-Birmingham, Birmingham, AL
VU University Medical Center, Amsterdam, The Netherlands
Charite University Med-Berlin, Berlin, Germany
Ctr Arthritis & Osteoporosis, Elizabethtown, KY
Horizon Pharma GmbH, Mannheim, Germany
Horizon Pharma GmbH, Mannheim, Germany
Horizon Pharma, Inc., Northbrook, IL
Med. University Dept. of Rheumatology, Wroclaw, Poland
NZOZ Centrum Medyczne, Bialystok, Poland
OEC, Budapest, Hungary

Background:

In patients with rheumatoid arthritis (RA), nocturnal increases in proinflammatory cytokines are implicated in the typical early morning symptoms, joint stiffness and pain. Glucocorticoid (GC) chronotherapy with a novel modified-release (MR) prednisone tablet enables delivery of prednisone during the night to specifically target the nocturnal rises in inflammatory mediators and symptoms. This novel approach has shown clinically relevant reduction of morning stiffness (MS) compared to conventional, immediate-release (IR) prednisone, thereby improving the benefit-risk ratio of GC therapy. Here we present efficacy and safety data of low-dose prednisone chronotherapy in patients with RA, not adequately controlled by disease-modifying antirheumatic drug (DMARD) therapy.

Methods:

In this 12-week, double-blind, placebo (PBO)-controlled study, patients (n=350) were randomized 2:1 to receive MR prednisone 5 mg or PBO once daily in the evening in addition to their standard RA therapy. The primary endpoint was the percentage of patients achieving a 20% improvement in RA signs and symptoms according to American College of Rheumatology criteria (ACR20) at week 12. A key secondary objective was the relative reduction of MS at week 12. Secondary efficacy endpoints included ACR50 and ACR70 responses, and other measures of clinical efficacy, inflammatory markers, adverse events (AEs) and other safety parameters.

Results:

Compared to PBO + DMARD, MR prednisone + DMARD treatment produced a higher ACR20 response (48.5% vs 28.6%, P<0.001), a higher ACR50 response (22.7% vs 9.2%, P<0.003) and ACR 70 response (7.0% vs 2.5%, P<0.1) at week 12. Greater improvements were also seen in morning symptoms and in individual RA core set measures in the MR prednisone group vs. PBO group at week 12. The incidence of adverse events (AEs) on MR prednisone was similar to PBO (43% vs 49%), with more AEs related to RA signs and symptoms (arthralgia and RA flare) in the PBO arm than in the MR prednisone arm (29.4 % vs 16.9 %). There were no clinically relevant differences between treatment groups in vital signs, hematology, biochemistry values or in markers for bone turnover, osteocalcin and urine CTX I.

Conclusion:

Even at 5 mg per day, low-dose prednisone chronotherapy is effective in the treatment of signs and symptoms of RA with a short-term safety profile similar to placebo.

To cite this abstract, please use the following information:
Buttgereit, Frank, Mehta, Daksha P., Kirwan, John R., Szechinski, Jacek, Boers, Maarten, Alten, Rieke, et al; Low-Dose Glucocorticoid Chronotherapy of Rheumatoid Arthritis: 12 Week Efficacy and Safety of Modified-Release (MR) Prednisone. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :392
DOI: 10.1002/art.28161

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