Prednisone delayed-release tablets approved for rheumatology indications

July 27, 2012

FDA has approved prednisone (Rayos, Horizon Pharma) delayed-release tablets (1 mg, 2 mg, and 5 mg) to treat a broad range of diseases including rheumatoid arthritis, polymyalgia rheumatica, psoriatic arthritis, ankylosing spondylitis, asthma, and chronic obstructive pulmonary disease.

FDA has approved prednisone (Rayos, Horizon Pharma) delayed-release tablets (1 mg, 2 mg, and 5 mg) to treat a broad range of diseases including rheumatoid arthritis (RA), polymyalgia rheumatica (PMR), psoriatic arthritis (PsA), ankylosing spondylitis (AS), asthma, and chronic obstructive pulmonary disease (COPD).

The FDA approval was supported by data bridging the pharmacokinetics of prednisone delayed-release tablets to immediate-release prednisone and data from the Circadian Administration of Prednisone in RA (CAPRA-1 and 2) trials. The CAPRA-2 trial, demonstrated that people with moderate to severe RA treated with prednisone delayed-release tablets experienced a statistically significant improvement in ACR20 response criteria compared to placebo (47% vs 29%; P=.001).

Results from CAPRA-2 also demonstrated a statistically significant improvement in ACR50 response compared to placebo (22% vs 10%; P=.007) and an improvement in the more stringent ACR70 response criteria (7% vs 3%; P=.0984). Both ACR50 and ACR70 were pre-specified secondary end points.

The relative change from baseline in the duration of morning stiffness at 12 weeks was assessed as a pre-specified secondary end point. Patients treated with prednisone delayed-release tablets had a median decrease in the duration of morning stiffness of 55 minutes compared to 33 minutes in placebo-treated patients (20-minute estimated median difference between treatment groups with 95% CI [7, 32; P=.001]).

Results from CAPRA-2 are published in Annals of the Rheumatic Diseases.

"Prednisone is a common therapy for patients with various inflammatory diseases, including RA, and the delayed-release enhancement offered with Rayos is an important treatment advance," said Michael Schiff, MD, clinical professor of medicine at the University of Colorado School of Medicine, Rheumatology Division, in a company release. "Rayos is engineered to benefit the underlying patterns of inflammatory diseases. Rayos, as studied in its clinical trials with 10 p.m. dosing, reduces the overnight rise of inflammatory mediators, which results in less pain and stiffness for patients as they begin their day."

The safety of prednisone delayed-release tablets was based on the evaluation of 375 RA patients in two controlled trials. Patients treated with prednisone delayed-release tablets ranged in age from 20 to 80 years (median age, 56 years). Patients were predominantly Caucasian and 85% were female.

Included in these safety results were data from the CAPRA-1 trial, a 12-week, double-blind, placebo-controlled study that evaluated 288 RA patients. CAPRA-1 compared 10 p.m. administration of prednisone delayed-release tablets with the morning administration of immediate-release prednisone at the same individual dose (average dose of 6.7 mg). Following the 12-week CAPRA-1 study, patients were followed in a 9-month, open-label extension study, which included 249 RA patients, 219 of whom completed the extension study. Patients received prednisone delayed-release tablets 3 mg to 10 mg once daily at 10 p.m.; the majority (84%) received 5 mg or less.

The clinical trial experience did not raise any safety concerns beyond those already established for immediate-release prednisone.

Results from the CAPRA-1 12-week study and the 9-month open-label extension are published in The Lancet and Annals of the Rheumatic Diseases, respectively.

Prednisone delayed-release tablets are contraindicated in patients who have known hypersensitivity to prednisone or to any of the excipients. Rare instances of anaphylaxis have occurred in patients receiving corticosteroids.