Positive results have been reported from the second phase III trial of Lodotra™ (single-pulse delayed-release low-dose prednisone tablet) in rheumatoid arthritis (RA).

Lodotra is claimed to provide all the benefits of standard immediate release prednisone but has the advantage of significantly reducing morning symptoms. The diurnal rhythm in RA is characterised by elevated night time levels of inflammatory cytokines, which leads to extreme stiffness and pain in the hours immediately after waking. These morning symptoms can be treated with prednisone administered at 2am. Lodotra’s delivery system ensures rapid release of the prednisone from the tablet core about 4 hours after ingestion and so administration at bed time results in a release of prednisone at about 2am for more effective treatment of the morning symptoms.

The CAPRA-2 study (Circadian Administration of Prednisone in Rheumatoid Arthritis-2) was a 12-week, trial conducted in 350 patients, with inadequate responses to DMARD therapy, who were randomised to receive either Lodotra (5mg/d), or placebo in addition to existing therapy. The primary efficacy endpoint was the ACR-20 response rate (20% improvement in a number of disease-specific criteria). The key secondary endpoint was the change in the duration of morning stiffness of the joints.

An ACR-20 response of 49% was reported in the Lodotra group vs. 29% in the placebo group (p=0.0002). The reduction of morning stiffness was 44% in the Lodotra group vs. 21 % in the placebo group (p=0.0008). The number of adverse events was reported to be low and comparable in both groups.

Lodotra was approved in the EU in January 2009 for the treatment of rheumatoid arthritis and associated morning stiffness. The CAPRA-2-data will be used to file for US marketing approval together with the data already available from the CAPRA-1 phase III trial which reported the superiority of Lodotra over standard prednisone treatment.