Horizon Pharma, Inc., a biopharmaceutical company, has announced an additional analysis of data from the pivotal Circadian Administration of Prednisone in rheumatoid arthritis-2, or CAPRA-2, clinical trial demonstrating that patients with active rheumatoid arthritis treated with the company's RAYOS 5mg delayed-release tablets had a significant improvement in reduction of fatigue, as determined by the Functional Assessment of Chronic Illness Therapy - Fatigue, or FACIT-F, questionnaire.
The efficacy of RAYOS in the treatment of rheumatoid arthritis (RA) was assessed in the CAPRA-2 trial, a double-blind, placebo-controlled, randomized, 12-week trial in patients with active rheumatoid arthritis diagnosed according to American College of Rheumatology (ACR) criteria.
Enrolled patients were not currently being treated with corticosteroids but did receive non-biologic disease-modifying antirheumatic drug (DMARD) therapy for at least 6 months prior to receipt of study medication. Patients were randomized in a 2:1 ratio to treatment with RAYOS 5 mg (n=231) or placebo (n=119). in addition to their DMARD therapy. Patients ranged in age from 27 to 80 years (median age 57 years) old, were predominantly Caucasian and were predominately (84%) female.
The primary endpoint was the proportion of patients achieving ACR20 response after 12 weeks. A key secondary endpoint was to compare treatment with RAYOS 5 mg and placebo in the change from baseline on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire, a 13-item questionnaire that assesses the effect of fatigue on daily activity and function on a 5-point scale.
In CAPRA-2, the mean baseline FACIT-F fatigue score was comparable between patients in the RAYOS 5 mg treatment group and patients in the placebo group (29 vs. 29). The least square mean (LSM) absolute increase from baseline to Week 12 was greater in patients in the RAYOS 5 mg treatment group compared to patients in the placebo group (3.8 vs.1.6), which indicated a reduction of fatigue. The difference in FACIT-F score between baseline and Week 12 was viewed as clinically relevant for patients in the RAYOS 5 mg treatment group, but not for patients in the placebo group (Cella et. al., 2005).
At Week 12, the LSM change from baseline was statistically significantly greater for patients in the RAYOS 5 mg treatment group than for patients in the placebo group (LSM difference=2.2 [95% CI: 0.8, 3.7], p-value=0.003). The improvement in FACIT-F score was consistent with improvement in ACR20 score.
There were no safety concerns for RAYOS 5 mg shown in the study beyond those already established for immediate-release prednisone.
RAYOS, known as LODOTRA in Europe, is a delayed-release formulation of low-dose prednisone. The pharmacokinetic profile of RAYOS is different with an approximately four-hour lag time from that of immediate-release prednisone formulations.
"Fatigue is one of the most common symptoms of RA and it often signals the onset of joint inflammation," said Dr Rieke Alten, chief of the internal medicine division, Schlosspark Clinic, Berlin. "In the US, approximately 50 percent of patients with severe RA are prescribed combination therapy that includes corticosteroids, with prednisone being the most common. Based on the CAPRA-2 data, RAYOS is a viable treatment option to help treat RA patients' inflammation as well as improve their symptoms, including fatigue."