Thursday, December 3, 2015

Modified-Release Prednisone at the ACR 2015 Meeting in San Francisco


There has been one study on Modified-Release Prednisone at the ACR 2015 Annual Meeting in San Francisco. I have voiced my concerns about Modified-Release Prednisone before and this study makes me even more confident in my views.

Maurizio Cutolo and colleagues presented: “Efficacy and Safety of Modified-Release Prednisone in Patients with Polymyalgia Rheumatica: Results of a Multicenter, Randomized, Active-Controlled Phase 3 Study”. Methods: “Patients meeting the 2012 EULAR/ACR classification criteria for PMR (excluding US) were randomized to double-blind MR prednisone or IR prednisone 15 mg/day for 4 weeks. MR prednisone/placebo was taken at approx. 10pm and IR prednisone/placebo was taken between 5am and 9am. […]” The duration of the study is too short to say anything about adverse events in long term therapy using glucocorticoids. Comparing “ approx. 10pm” with “between 5am and 9am” looks suspicious as one compares an optimized time slot with one that wasn’t optimized. Why compare approx. 10pm and approx. 5am? Results: “The study randomized 62 patients; 66% female, mean age 69 years. […].” I’d say the study is very low powered. Conclusion: “Although the primary analysis of non-inferiority was not met, the consistently positive and clinically meaningful results for MR prednisone compared with IR prednisone observed in this study provide an indication of a beneficial clinical effect of MR over IR prednisone in patients with PMR, with improvements observed as early as Week 1.”

My own conclusion is different: “Although Modified-Release Prednisone has been given an advantage, the primary analysis of non-inferiority was not met.” Especially morning stiffness, global pain, and CRP didn’t show significant differences (please look at the chart in the abstract). If you really want to test, if the modified-release mechanism has any advantage over prednisone, you would have to give both at the same time in the evening. 

References:
Cutolo M, Hopp M, Liebscher S, Dasgupta B, Buttgereit F. Efficacy and Safety of Modified-Release Prednisone in Patients with Polymyalgia Rheumatica: Results of a Multicenter, Randomized, Active-Controlled Phase 3 Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/efficacy-and-safety-of-modified-release-prednisone-in-patients-with-polymyalgia-rheumatica-results-of-a-multicenter-randomized-active-controlled-phase-3-study/. Accessed December 3, 2015.
Lodotra (modified or delayed release prednisone) at the ACR 2013 Meeting in San Diego http://rheumatologe.blogspot.de/2013/11/lodotra-modified-or-delayed-release.html


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