Monday, November 4, 2013

Lodotra (modified or delayed release prednisone) at the ACR 2013 Meeting in San Diego

Let me talk again about modified or delayed release prednisone (Lodotra) as two studies have been presented at the ACR 2013 Meeting in San Diego.

F. Buttgereit and colleagues presented this study [Abstract # 2255]: "Threshold Analysis of Patient Reported Morning Stiffness Where Delayed-Release (DR) Prednisone Was Compared to, and Replaced, Immediate Release Prednisone in Rheumatoid Arthritis (RA) Patients Receiving Conventional Disease-Modifying Antirheumatic Drugs (DMARDs) Over 1 Year." IR-prednisone, taken in the morning, is compared to DR-prednisone, taken once daily at bedtime (e.g. 10pm). Conclusion: DR prednisone, as compared to IR prednisone, produces significantly higher MS response rates as defined by 25/50/75% improvement thresholds.  [...]."
The same patients were analysed in this study, which had been presented by R. Alten and colleagues [Abstract # 2265]: "Switching From Immediate Release (IR) Prednisone To Delayed Release (DR) Prednisone Improves Patient Reported Outcomes In Rheumatoid Arthritis (RA) Patients On Conventional Disease-Modifying Antirheumatic Drugs (DMARDs)." Conclusion: "This analysis demonstrates that RA patients on stable DMARD therapy, who have not adequately responded to IR-prednisone with respect to morning stiffness, showed statistically significant and clinically meaningful improvement in this symptom when switched to DR prednisone [...]."

Where's the catch? There's more than one. First: would you call a patient, who suffers two hours of morning stiffness, stable? Second: the advocates of Lodotra claim chronotherapy for their therapy, but we're already doing chronotherapy. We give immediate release prednisone in the morning to optimize (reduce) side effects. Lodotra is given in the evening to be released during the night to optimize (increase) therapeutic effects. In any study designed as this study DR prednisone will be better than IR prednisone. This is due to the time, when the drug is given. So the study shows that prednisone given at different times has different effects on morning stiffness. If you really want to test, if the DR mechanism has any advantage over IR prednisone, you would have to give both at the same time in the evening. My guess is that significance dwindles to a trend. Unless I see such a designed study, I won't prescribe DR prednisone.

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