Atorvastatin added to interferon beta for relapsing multiple sclerosis: 12-month treatment extension of the randomized multicenter SWABIMS trial

Christian P Kamm, Marwan El-Koussy, Sebastian Humpert, Oliver Findling, Yuliya Burren, Guido Schwegler, Filippo Donati, Martin Müller, Felix Müller, Johannes Slotboom, Ludwig Kappos, Yvonne Naegelin, Heinrich P Mattle, SWABIMS Study Group, Barbara Rieder, Maaike Gafner, Simon Jung, Stefan Kipfer, Stefan Wolff, Martin Zbinden, Claus Kiefer, Ferdinand von Bredow, Roland Wiest, Gerhard Schroth, Manuela Leichtle, Barbara Kieser, Michele Alfaro, Marianne Braunschweig, Petra Stellmes, Thomas Treumann, Prisca Wicki, Ludwig Schelosky, Klaus-Wilhelm Stock, Martina Nuding, Christian P Kamm, Marwan El-Koussy, Sebastian Humpert, Oliver Findling, Yuliya Burren, Guido Schwegler, Filippo Donati, Martin Müller, Felix Müller, Johannes Slotboom, Ludwig Kappos, Yvonne Naegelin, Heinrich P Mattle, SWABIMS Study Group, Barbara Rieder, Maaike Gafner, Simon Jung, Stefan Kipfer, Stefan Wolff, Martin Zbinden, Claus Kiefer, Ferdinand von Bredow, Roland Wiest, Gerhard Schroth, Manuela Leichtle, Barbara Kieser, Michele Alfaro, Marianne Braunschweig, Petra Stellmes, Thomas Treumann, Prisca Wicki, Ludwig Schelosky, Klaus-Wilhelm Stock, Martina Nuding

Abstract

Background: Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects.

Objectives: To report the 12-month extension of a phase II trial evaluating the efficacy, safety and tolerability of atorvastatin 40 mg/d added to interferon beta-1b (IFNB-1b) in relapsing-remitting multiple sclerosis (RRMS).

Methods: In the randomized, multicenter, parallel-group, rater-blinded core study, 77 RRMS patients started IFNB-1b. At month three they were randomized 1∶1 to receive atorvastatin 40 mg/d or not in addition to IFNB-1b until month 15. In the subsequent extension study, patients continued with unchanged medication for another 12 months. Data at study end were compared to data at month three of the core study.

Results: 27 of 72 patients that finished the core study entered the extension study. 45 patients were lost mainly due to a safety analysis during the core study including a recruitment stop for the extension study. The primary end point, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.926; 95% CI 0.265-14.0007; p = 0.51). All secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of Gd-enhancing lesions on T1-weighted images, volume of grey and white matter, EDSS, MSFC, relapse rate, number of relapse-free patients and neutralizing antibodies did not show significant differences either. The combination therapy was well tolerated.

Conclusions: Atorvastatin 40 mg/day in addition to IFNB-1b did not have any beneficial effects on RRMS compared to IFNB-1b monotherapy over a period of 24 months.

Trial registration: ClinicalTrials.gov NCT01111656.

Conflict of interest statement

Competing Interests: The authors have read the journal’s policy and have the following conflicts: This study was funded by Bayer Schering Pharma (Switzerland) and Pfizer (Switzerland). Dr Kamm has received honoraria for lectures and consulting from Biogen-idec, Novartis, Bayer Schweiz AG, Teva, Merck-Serono, Genzyme and Pfizer. Dr Humpert has received honoraria for lectures from Biogen-Dompé, Merck-Serono and Novartis. Dr. Donati has received honoraria for consulting from Merck-Serono, Pfizer and Teva. Dr Findling, Dr von Bredow, Ms Burren, Dr Schwegler, Drs Müller, Dr Slotboom and Dr Naegelin have no competing interests. Prof Kappos received research support from the Swiss National Research Foundation, the Swiss MS Society, and from the Gianni Rubatto Foundation (Zurich); has served on scientific advisory boards and his Department at the University Hospital Basel has received research support from Acorda Therapeutics Inc., Actelion Pharmaceuticals Ltd, Abbott, AstraZeneca, Bayhill Therapeutics, Bayer Schering Pharma, Biogen Idec, Boehringer Ingelheim, Centocor Ortho Biotech Inc., Eisai Inc., Genzyme Corporation, GlaxoSmithKline, The Immune Response Corporation, MediciNova, Inc., Neurocrine Biosciences, Novartis, sanofi-aventis, Merck Serono, Roche, Teva Pharmaceutical Industries Ltd., UCB, and Wyeth. Prof Mattle has received honoraria for lectures and consulting from Bayer-Schering, Biogen-Dompé, Genzyme, Merck-Serono, TEVA, Sanofi-Aventis, Novartis and Pfizer. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. CONSORT Flow diagram showing enrollment,…
Figure 1. CONSORT Flow diagram showing enrollment, allocation and follow-up of patients in the SWABIMS and SWABIMS Extension Study.

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