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Radiologic MS disease activity during natalizumab treatment interruption: findings from RESTORE

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Abstract

The objective of this study is to characterize the timing and extent of radiologic MS disease recurrence during the 24-week natalizumab treatment interruption period in RESTORE. RESTORE was a randomized, partially placebo-controlled exploratory study. Natalizumab-treated patients with no gadolinium-enhancing (Gd+) lesions at screening (n = 175) were randomized 1:1:2 to continue natalizumab (n = 45), switch to placebo (n = 42), or switch to other therapies (n = 88) for 24 weeks. MRI assessments were performed every 4 weeks. Predictors of increased numbers of Gd+ lesions during natalizumab treatment interruption were evaluated. The numbers of Gd+ lesions were compared with retrospectively collected pre-natalizumab MRI reports and data from placebo-treated patients from two historical randomized clinical trials. Gd+ lesions were detected in 0 % (0/45) of natalizumab patients, 61 % (25/41) of placebo patients, and 48 % (39/81) of other-therapies patients during the randomized treatment period. Gd+ lesions were detected starting at week 12; most were observed at week 16 or later. Thirteen percent (14/107) of patients had >5 Gd+ lesions on ≥1 (of 6) scans during the randomized treatment period versus 7 % (7/107) of patients pre-natalizumab (based on medical record of a single scan). Younger patients and those with more Gd+ lesions pre-natalizumab were more likely to have increased MRI activity. Distribution of total and persistent Gd+ lesions in RESTORE patients was similar to placebo-treated historical control patients. In most patients, recurring radiological disease activity during natalizumab interruption did not exceed pre-natalizumab levels or levels seen in historical control patients.

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Acknowledgments

Biogen Idec provided funding for editorial support in the development of this paper; Britt Anderson, PhD, from Infusion Communications wrote the first draft of the manuscript based on input from authors, and Josh Safran and Jackie Cannon from Infusion Communications copyedited and styled the manuscript per journal requirements. Biogen Idec reviewed and provided feedback on the paper to the authors. The authors had full editorial control of the paper and provided their final approval of all content. This study was funded by Biogen Idec Inc.

Conflicts of interest

Dr. Kaufman has received honoraria and research support from Biogen Idec, has received financial support from Bayer, EMD Serono, Novartis, and Teva, and is a consultant for Department of Defense. Dr. Cree has received consulting honoraria from AbbVie, Biogen Idec, EMD Serono, Genzyme, Novartis, Sanofi, and Teva Neurosciences. Dr. De Sèze has received honoraria from Bayer Schering, Biogen Idec, LFB, Merck Serono, Novartis, Sanofi, and Teva. Dr. Fox has received consultant fees from Allozyne, Avanir, Biogen Idec, EMD Serono, Novartis, Questcor, Teva, and Xenoport and has received research support from Biogen Idec and Novartis. Dr. Gold has received research support and honoraria from Bayer HealthCare, Biogen Idec, Merck Serono, and Teva, is Editor-in-Chief of Therapeutic Advances in Neurological Disorders, has received a license fee from Biogen Idec (no future rights), and has received research support from Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva. Dr. Hartung has received honoraria for consulting and speaking at symposia from Bayer HealthCare, Biogen Idec, BioMS, Genzyme, Merck Serono, Novartis, Roche, Sanofi, and Teva. Dr. Jeffery is a consultant for Acorda, Bayer HealthCare, EMD Serono, Genzyme, GlaxoSmithKline, Novartis, Pfizer, Questcor, and Teva, and has received research support from Berlex, Biogen Idec, Novartis, Pfizer, and Teva. Dr. Kappos has received research support from Acorda, Actelion, Allozyne, BaroFold, Bayer HealthCare, Bayer Schering, Bayhill, Biogen Idec, Boehringer Ingelheim, Elan, Genmab, GlaxoSmithKline, Glenmark, Merck Serono, MediciNova, Novartis, Sanofi, Santhera, Shire, Roche, Teva, UCB, Wyeth, the Swiss MS Society, the Swiss National Research Foundation, the European Union, the Gianni Rubatto Foundation, and the Novartis and Roche Research Foundations. Dr. Montalbán has received speaking honoraria and travel expenses for scientific meetings, has been a steering committee member of clinical trials, or has participated in advisory boards of clinical trials in the past years with Almirall, Bayer Schering, Biogen Idec, EMD Merck Serono, Genentech, Genzyme, Novartis, Sanofi, and Teva. Dr. Weinstock-Guttman has received honoraria for speaking and serving on scientific advisory boards from Acorda, Biogen Idec, EMD Serono, Novartis, Pfizer, and Teva and has received financial support for research from Acorda, Biogen Idec, EMD Serono, Novartis, Pfizer, and Teva. Drs. Duda and Ticho were employees of Biogen Idec at the time of the study and manuscript preparation. Drs. Pace and Campagnolo are employees of Biogen Idec.

Ethical standard

Each site’s institutional review board reviewed and approved the study protocol and amendments, and all participants provided written informed consent. The RESTORE study was performed in accordance with the Declaration of Helsinki and International Conference on Harmonisation Guideline on Good Clinical Practice.

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Authors and Affiliations

  1. MS Center, Carolinas Medical Center, 1010 Edgehill Road North, Charlotte, NC, 28207, USA

    Michael Kaufman

  2. University of California San Francisco Multiple Sclerosis Center, San Francisco, CA, USA

    Bruce A. C. Cree

  3. Hôpital Civil, Strasbourg, France

    Jerome De Sèze

  4. Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH, USA

    Robert J. Fox

  5. St. Josef Hospital, Ruhr University, Bochum, Germany

    Ralf Gold

  6. Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany

    Hans-Peter Hartung

  7. Piedmont HealthCare, Mooresville, NC, USA

    Douglas Jeffery

  8. Departments of Neurology and Biomedicine, University Hospital Basel, Basel, Switzerland

    Ludwig Kappos

  9. Vall d′Hebron University Hospital, Barcelona, Spain

    Xavier Montalbán

  10. Jacobs MS Center and Pediatric MS Center of Excellence, Jacobs Neurological Institute, Buffalo, NY, USA

    Bianca Weinstock-Guttman

  11. Pfizer Inc., New York, NY, USA

    Barry Ticho

  12. Sarepta Therapeutics, Cambridge, MA, USA

    Petra Duda

  13. Biogen Idec Inc., Cambridge, MA, USA

    Amy Pace & Denise Campagnolo

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  1. Michael Kaufman
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  2. Bruce A. C. Cree
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  3. Jerome De Sèze
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  7. Douglas Jeffery
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  8. Ludwig Kappos
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  9. Xavier Montalbán
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  10. Bianca Weinstock-Guttman
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  11. Barry Ticho
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  12. Petra Duda
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  13. Amy Pace
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  14. Denise Campagnolo
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Corresponding author

Correspondence to Michael Kaufman.

Additional information

Drs. Ticho and Duda are former employees of Biogen Idec Inc. and were at the company during study conduct.

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Kaufman, M., Cree, B.A.C., De Sèze, J. et al. Radiologic MS disease activity during natalizumab treatment interruption: findings from RESTORE. J Neurol 262, 326–336 (2015). https://doi.org/10.1007/s00415-014-7558-6

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  • DOI: https://doi.org/10.1007/s00415-014-7558-6

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