Modified-release Prednisone

Modified-release prednisone is marketed in Germany as Lodotra, which is at least fourfold as expensive as conventional immediate-release prednisone, but often it is even more expensive when it comes to tapering dosage.

C. Baerwald et al. presented a non-interventional study of patients with rheumatoid arthritis (n=2661), but looks only at a subgroup of 928 patients. The authors choose to leave the patients on conventional immediate-release prednisone without evaluation (N=1733). Did the 1733 patients on conventional immediate-release prednisone fare so well that a comparison would be destastrous? The authors concluded that patients treated with modified-release prednisone tablets benefited. I don´t doubt this, but I doubt the relevance of this study.

[AB0594] FUNCTIONAL ABILITY AND QUALITY OF LIFE IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH LOW DOSE MODIFIED-RELEASE PREDNISONE IN DAILY PRACTICE
C. Baerwald1, F. Buttgereit2, J. Währisch3, P. Flaxenberg3. 1Medical Clinic and Polyclinic, University Hospital, Leipzig; 2Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin; 3Specialist in Internal Medicine and Rheumatology, Essen, Germany
Conclusions: In this non-interventional study patients treated with modified-release prednisone tablets benefited from better functional ability and Quality of Life being shown under daily practice conditions. These results add to those obtained from previous clinical studies.

S. Zakout and colleagues looked at the circadian rhythm of IL-6 in patients with polymyalgia rheumatica and compared the effects of morning (immediate-release prednisone) and night time glucocorticoids (modified-release prednisone) on overnight IL-6 and morning stiffness. With N=10 this study is underpowered, but in the conclusions the authors only “raise the possibility” of better disease control. Maybe one can indeed start at a lower dose, but inflammation needs to be tightly controlled in patients with polymyalgia rheumatica, so that conventional immediate-release prednisone achieves the same.
For the time being conventional immediate-release prednisone is easier to taper as modified-release prednisone tablets can´t be broken. Therapy costs might increase up to sixteenfold depending on how you taper dosage.

[AB0103] POLYMYALGIA RHEUMATICA HAS A NOCTURNAL RISE IN PLASMA INTERLEUKIN-6 WHICH IS ALMOST COMPLETELY SUPPRESSED BY NIGHT TIME ADMINISTRATION OF MODIFIED-RELEASE PREDNISONE
S. Zakout1, L. Clark1, D. Jessop2, R.H. Straub3, J.R. Kirwan1. 1Rheumatology, University Hospitals Bristol; 2Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, United Kingdom; 3Lab of Experimental Rheumatology & Neuroendocrine Immunology, University Hospital, Regensburg, Germany
Conclusions: PMR, like RA, has a marked circadian variation in plasma IL-6. Both IL-6 and symptoms of morning stiffness are suppressed more by night time low dose glucocorticoids. This observation raises the possibility that PMR may be controlled by lower doses of glucocorticoids given at night compared to current conventional morning treatment.


L. Iaccarino1 and colleagues presented a study, which might be labeled chaotic. They looked at 1928 consecutive outpatients with documented rheumatoid arthritis, in which 950 patients were changed to modified-release prednisone for unclear reasons. Patients have been on different DMARDs and even biologics, but nothing is told on dosage variation, change of therapy. The study also fails to compare patients on modified-release prednisone with patients on conventional immediate-release prednisone.

[OP0206] EFFICACY OF MODIFIED-RELEASE PREDNISONE IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA) CHRONICALLY TREATED WITH STANDARD GLUCOCORTICOIDS: AN ITALIAN MULTICENTER SURVEY
L. Iaccarino1, I. Farina2, A. Sulli3, A. Bortoluzzi2, C. Marcassa4, A. Doria1, M. Govoni2, M. Cutolo3. 1Division of Rheumatology, University of Padova, Padova; 2Rheumatology Unit, University of Ferrara, Ferrara; 3Research Laboratory and Academic Rheumatology, University of Genova, Genova; 4Fondazione Maugeri IRCCS, Veruno (NO), Italy
Conclusions: In unselected RA patients chronically treated with standard GC, modified-release prednisone (given at bedtime) induced a significant improvement over a medium-term observation, particularly in those patients who switched from methyl-prednisolone.


S. Stisi ans colleagues presented a study, which has been constructed like the study by L. Iaccarino. The study shows that prednisone works in patients with uncontrolled activity of rheumatoid arthritis. Wow! Nobody expected this! If modified-release prednisone is necessary to do the trick or conventional immediate-release prednisone or changing DMARDs can´t be answered by this study.

[AB0610] MID-TERM EFFICACY OF MODIFIED-RELEASE PREDNISONE IN GLUCOCORTICOIDS-NAIVE PATIENTS WITH RHEUMATOID ARTHRITIS (RA)
S. Stisi1, R. De Luca Bossa2, G. Ciano3, A. Marsico4, C. Venditti1, C. Marcassa5. 1Medical Sciences, Rheumatology Division, Gaetano Rummo Hospital - Benevento, Benevento; 2Asl Sa1, Laurito; 3Medical Sciences, Division of Internal Medicine, Ariano Irpino; 4Rheumatology Unit, Taranto; 5Cardiology, S. Maugeri Fnd, IRCCS, Veruno, Italy
Conclusions: In unselected RA patients on active antirheumatic treatment, modified-release prednisone (given at bedtime) induced a substantial benefit over a medium-term observation and was well tolerated.

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.