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news.Horizon Pharma has revealed the results from the extended open label portion of The Circadian Administration of Prednisone in Rheumatoid Arthritis-1 (CAPRA-1) Phase 3 European registration study of Lodotra, a programmed release formulation of low-dose prednisone, showed improvement in reducing the duration of morning stiffness in patients with Rheumatoid Arthritis (RA) over a 12 month period.
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The CAPRA-1 study of Lodotra assessed 288 patients with active RA in a 12-week, randomised, double-blind, placebo-controlled trial comparing bedtime administration of Lodotra with morning administration of immediate release (IR) prednisone at the same individual dose (an average dose of 6.7mg).
Following the double-blind portion of the study, 249 patients continued on to an open label extension study for up to nine additional months, during which all patients received only an evening dose of Lodotra.
Variables assessed in the study included reduction in the duration of morning stiffness (MS) of the joints, disease activity scores (DAS 28), a measurement of pain and swelling in 28 joints typically impacted by RA, American College of Rheumatology (ACR) 20 response rate, which measures the percentage of patients who have achieved a 20% improvement in tender and swollen joint counts as well as a 20% improvement in three of five other criteria of disease activity and plasma levels of interleukin-6 (IL-6), a pro-inflammatory cytokine.
Reportedly, following six months of treatment in the open label portion of the study, morning stiffness was reduced in those patients who were in the IR prednisone group during the double-blind portion by 54% compared to 56% for patients taking Lodotra in both portions of the study.
Additionally, at 12 months, the mean relative reduction in morning stiffness reached 55% in patients treated with Lodotra who continued treatment from the double-blind phase compared to 45 percent in the patient group who had switched from IR prednisone to Lodotra.
Of patients who completed a total of 12 months in the study, 37% achieved improvement in the ACR20 criteria. DAS 28 score was reduced from the mean 5.8 at baseline to 4.8 for those taking Lodotra and to 4.9 for the former IR prednisone group. IL-6 plasma levels were approximately 50% less in the Lodotra-treated patients compared to the IR prednisone-treated patients after both three and 12 months of treatment.
Frank Buttgereit, lead author of the study, said: “The results from the open label portion of the CAPRA-1 study showed that the efficacy of glucocorticoid therapy can be sustained by synchronising the drug release with the circadian rhythm of the underlying inflammation and resulting symptoms.”
Jeffrey Sherman, executive vice president of development, regulatory affairs and chief medical officer of Horizon Pharma, said: “The results of this study suggest that low-dose programmed-release Lodotra may offer benefits over IR prednisone for the treatment of RA, and those benefits are maintained for up to 12 months.”