Monday, June 24, 2013

Modified Release Prednisone at the EULAR 2013

I have already published my concerns about modified release prednisone severeal times; please look for the links below.

At the EULAR 2012 Meeting there had been four studies: "To sum up these studies: Lodotra (modified-release prednisone) failed to show a clear advantage over conventional immediate-release prednisone in the studies presented at the 2012 EULAR meeting. One study failed to look at 1733 of 2661 patients, while another study only presented data on 950 of 1928 patients."

At the EULAR 2013 Meeting we could see two studies on modified release prednisone.

M. Benucci and colleagues presented [SAT0152]: "Polymyalgia rheumatica: a comparative study of methylprednisolone and the modified release prednisone". The study is non-blinded, non-randomized and looks only at N=42 in two groups. The endpoint is unclear. The objective is to " compare changes in inflammation markers and their correlations with cortisol levels ...". Conclusions: " In this non-randomized prospective observational study the response of inflammation markers to low-dose GC was similar in patients with PM treated with 6-MP or MR-P, and morning cortisol levels were unaffected. However, the patients treated with MR-P showed a greater decrease in IL-6 levels after the first month."
Does anyone treat IL-6 levels after the first month in patients with polymyalgia rheumatica? I don't! So this study rather convinces me to not use Lodotra.

D. Sola and colleagues presented a study [AB0346]: "Safety and efficacy of rheumatoid arthritis treatment with modified-release prednisone (MR-PDN), experience in “real life”". The study is retrospective! Objectives: "To assess in “real life” adherence to treatment and efficacy (morning stiffness, DAS28 score and steroid dose reduction) in RA patients who initiated treatment with MR-PDN,". "64 RA patients who initiated RM-PDN completed a 12 weeks (W) follow-up, 49 completed 24 W and 33 48W." So the study lost about 50% of it's initial patients to follow up after 48 weeks or is incomplete. "In 19 patients this was the first steroid treatment, 45 received MR-PDN after a switch from one other steroid (in this case 1 month bridging with traditional steroid was performed)." So, in about 33% of the patients we look at prednisone naive and in 66% at pretreated patients. At week 48 only 64% stayed on treatment. "The efficacy analysis was limited only to patients with DMARDs or biological therapies stable for the whole period of observation." But we don't know how many patients had been on which therapy. And in the end we look at patients, who have been doing better and measure the success. Conclusions: "In RA patients in “real life” the use of MR-PDN showed good safety profile and adherence to treatment also after switch from prolonged traditional steroid treatment. We observed a reduction in morning stiffness and disease activity similarly to that described in clinical trial. The greatest improvement occurs within the first 12 weeks confirmed by further modest improvement up to 48 weeks. Finally the use of the MR-PDN permitted a lower consumption of steroid in these patients with obvious long term benefits."
The study is a catastrophe. It looks retrospectively at a heterogenous group of patients (pretreated with steroids of steroid naive, on traditional DMARDs or on different biologics) without a well defined endpoint. Is it desirable to stay on prednisone after 48 weeks? Is the reduction of morning stiffness and disease activity due to modified release prednisone or DMARDs/biologics? What is the idea of the authors behind: lower consumption of steroid? Lower than at the beginning? That would mean modified release prednisone could be tapered like any other steroid. What are the "obvious long term benefits"?

These two studies convince me even more that modified release prednisone (Lodotra) won't be my drug of choice.

Links: (Text in German)

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