Nefrologia

Efficacy and safety of enteric-coated mycophenolate sodium in combination with two corticosteroid regimens for the treatment of active lupus nephritis
M. Zeher 1, A. Doria 2, J. Lan 3, G. Aroca 4, D. Jayne 5, I. Boletis6, F. Hiepe 7 , H Prestele8, P Bernhardt8, Z. Amoura9
1Institute for Internal Medicine, Debrecen, Hungary
2 Division of Rheumatology, Department of Clinical and ExperimentalMedicine, University of Padova, Padova, Italy
3Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China
4 Clínica de la Costa, Barranquilla, Colombia
5Addenbrooke's Hospital, Cambridge, United Kingdom
6Laiko Hospital, Athens, Greece
7Charité University Medicine, Berlin, Germany
8Novartis Pharma AG, Basel, Switzerland
9Pitie-Salpetriere Hospital, French National ReferenceCenter for SLE, Paris, France

Author for correspondence:
Margit Zeher, MD
3rd Department of Internal Medicine
Institute for Internal Medicine, University of Debrecen
Moricz Zsigmond 22
4004 Debrecen, Hungary
Tel: +36-52414-969 Fax: +36-52414-969 Email: zeher@iiibel.dote.hu
Running title: EC-MPS for lupus nephritis flare
Word count: 3,342
Grant support and conflicts of interest
The studywas funded by Novartis Pharma AG. IB and GA have received research funding from Novartis. FH has received research funding and travel grants from Novartis, and is a member of a Novartis Advisory Board. IB is a member of a Novartis Advisory Board. DJ has received research grant support from Vifor Pharma, and research grants support and lecture fees from Roche. HP and PB are employees of NovartisPharma AG. The other authors have no conflicts of interest to declare.
Acknowledgements
With grateful thanks to Reto Brambilla, Anne-Claire Marrast, Yolandi Joubert and Isabelle Indermuehle of Novartis; and to Caroline Dunstall for editorial support.
Abstract
Mycophenolic acid, in combination with corticosteroids, is a safe and effective treatment for lupus nephritis. Corticosteroid toxicitycontributes to morbidity and mortality. Gastrointestinal intolerance of enteric-coated mycophenolate sodium (EC-MPS) may be less than with the mycophenolate mofetil formulation. MyLupus was a 24-week, multicenter, open-label, study in patients with active proliferative lupus nephritis treated with EC-MPS, randomized to standard-dose (n=42) or reduced-dose (n=39) corticosteroids. Complete responseat week 24, the primary endpoint, occurred in 19.8% (16/81) of patients (19.0% [8/42] standard-dose, 20.5% [8/39] reduced-dose; lower limit of 97.5% CI for the difference -15.9%, p=0.098, i.e. non-inferiority was not shown). Partial response occurred in 42.0% of patients (34/81) (standard-dose 47.6% [20/42], reduced-dose 35.9% [14/39]; p=0.29). From baseline to week 24, mean global BILAG scoredecreased by 8.6±5.8 and 9.4±5.5 in the standard-dose and reduced-dose groups, respectively; mean SLEDAI score decreased by 10.4±7.3 and 9.4±9.1. The incidence of adverse events was 83.3% and 76.9% (serious adverse events 19.0% and 10.3%) in the standard-dose and reduced-dose groups, respectively. Three patients discontinued study medication due to adverse events. This exploratory study suggeststhat efficacy is similar when EC-MPS is used in combination with either standard-dose or low-dose corticosteroids as induction therapy for active lupus nephritis.
Introduction
Lupus nephritis is the most frequent clinical manifestation of systemic lupus erythematosus (SLE), occurring in approximately 40-50% of adults with the disease (1-3). It leads to end-stage renal disease in up to 20% ofcases (4) with an associated increase in mortality (5). Despite the high toll of lupus nephritis and progress in understanding of its pathogenesis, current treatment options remain limited. The introduction of combined therapy using cyclophosphamide and corticosteroids improved prognosis compared to corticosteroids alone (6), but both short- and long-term toxicity of the combination regimen are...