TY - JOUR
T1 - Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis
AU - Zivadinov, R.
AU - Reder, A. T.
AU - Filippi, M.
AU - Minagar, A.
AU - Stuve, Olaf
AU - Lassmann, H.
AU - Racke, M. K.
AU - Dwyer, M. G.
AU - Frohman, Elliot
AU - Khan, O.
N1 - Funding Information:
Dr. Zivadinov served as a consultant for Teva and Biogen. Dr. Zivadinov has served on the speakers’ bureaus of Teva and Biogen. Dr. Zivadinov has received honoraria from Teva, Biogen, EMD Serono, and Pfizer. Dr. Zivadinov has received research or grant support from Teva, Biogen, Aspreva, and Genzyme. Dr. Reder is on Advisory Board/Consultant for: Abbott Laboratories, Immunoscience, Parsippany, NJ; American Medical Association, Chicago, IL; Astra Merck, Wayne, PA; Athena Neurosciences, South San Francisco, CA; Aventis Pharma, Bridgewater, NJ; Berlex Laboratories, Richmond, CA; Biogen and Biogen/Idec, Cambridge, MA; BioMS Medical Corp., Edmonton, Alberta, Canada; Blue Cross, Blue Shield, Chicago, IL; Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT; Caremark Rx, Northbrook, IL; Centocor, Inc., Malvern, PA; Cephalon, Inc., Delaware, MD; Connectics/Connective Therapeutics, Palo Alto, CA; CroMedica Global Inc., Victoria, BC; Elan Pharmaceuticals, Inc., San Diego, CA; Genentech, South San Francisco, CA; Genzyme Corporation, San Antonio, TX; GlaxoSmithKline, Research Triangle Park, NC; Hoechst Marion Roussel Canada Research, Inc., Leval, Quebec; Hoffman-LaRoche, Nutley, NJ; Idec, San Diego, CA; Immunex, Seattle, WA; Institute for Health Care Quality, Minneapolis, MN; Johnson & Johnson, Pharmaceutical Research & Development, LLC, Raritan, NJ; Kalobios, San Francisco; NARCOMS, Yale University, New Haven, CT; Barrow Neurological Institute, Phoenix, AZ; National Multiple Sclerosis Society & Paralyzed Veterans of America, “Pain Panel,” New York, NY; Neurocrine Biosciences, San Diego, CA; Novartis Corporation, New York, NY; Parke-Davis, Morris Plains, NJ; Pfizer Inc., New York, NY; Pharmacia & Upjohn, Kalamazoo, MI; Protein Design Labs, Inc., Delaware; Quantum Biotechnologies, Inc., Leval, Quebec; Quintiles, Inc., San Diego, CA; RENEW study (post-marketing study of Novantrone in MS); Serono; Sandoz (now Novartis) & Novartis, East Hanover, NJ; Sention, Inc., Providence, RI; Serono, Norwell, MA; Smith Kline-Beecham, Philadelphia, PA; Specialized Therapeutics, a division of Berlipharm, Inc., Montville, NJ; Takeda Pharmaceuticals, Lincolnshire, IL; and Teva-Marion, Kansas City, MO. Dr. Filippi has served as a consultant for Teva, Bayer Schering AG, Genmab, Biogen Dompe, and Merck Serono. Dr. Filippi has served on the speakers’ bureaus of Teva, Bayer Schering AG, Genmab, Biogen Dompe, and Merck Serono. Dr. Filippi has received personal compensation from Teva, Bayer Schering AG, Genmab, Biogen Dompe, and Merck Serono. Dr. Filippi has received grant or contract support from Teva, Bayer Schering AG, Genmab, Biogen Dompe, and Merck Serono. Dr. Minagar has received research or grant support from Biogen, Bayer, and EMD Serono. Dr. Stüve has served as a consultant for Teva, EMD Serono, Novartis, and Genentech. Dr. Stüve has served on the speakers’ bureaus of Teva, and EMD Serono. Dr. Stüve has receved personal compensation from Teva, EMD Serono, Novartis, and Genentech. Dr. Lassmann has served on the advisory board for future drug development for Bayer/Schering. Dr. Lassman has received honoraria for lectures from Serono, Teva/Aventis, and Biogen. Dr. Racke has served as a consultant for Peptimmune, Teva, and Bristol Myers Squib. Dr. Racke has received honoraria from Teva, Bayer, EMD Serono, and Genentech. Dr. Racke has received research or grant support from Bayer, Genentech, Biogen, and Teva. Dr. Dwyer reports no disclosures. Dr. Frohman has served as a consultant for Teva and Biogen. Dr. Frohman has served on the speakers’ bureaus of Biogen, Teva, and Bayer. Dr. Khan as received honoraria from Teva, Biogen, and EMD Serono. Dr. Khan has received research or grant support from Teva, Biogen, EMD Serono, and Bayer Health Care.
PY - 2008/7/8
Y1 - 2008/7/8
N2 - Disease-modifying agents (DMAs), including interferon beta (IFNj3) and glatiramer acetate (GA), are the mainstays of long-term treatment of multiple sclerosis (MS). Other potent antiinflammatory agents like natalizumab and different types of chemotherapeutics are increasingly being used for treatment of MS, particularly in patients with breakthrough disease activity. Brain volume (BV) loss occurs early in the disease process, accelerates over time, and may be only partially affected by DMA therapy. Low-dose, low frequency IFN/3 administered once weekly and GA appear to partially reduce BV decline over the second and third years of treatment. High dose, high frequency IFN/3 demonstrated no clear effect on BV loss during this time period. Current evidence suggests that changes in BV after immunoablation may not be due entirely to the reso-ution of edema but may be related to potential chemotoxicity of high dose cyclophosphamide. Natalizumab reduces the development of BV decline in the second and third years of treatment. IV immunoglobulin showed a positive effect on decelerating BV reduction in relapsing and advanced stages of MS. These differences between DMAs may be explained by the extent of their therapeutic effects on inflammation and on the balance between inhibition or promotion of remy-elination and neuronal repair in the CNS. We described the mechanisms of action by which DMAs nduce accelerated, nontissue-related BV loss (pseudoatrophy) in the short term but, in the long run, may still potentially lead to permanent BV decline. The effects of corticosteroid therapy on changes in BV in patients with MS help clarify the mechanisms through which potent antiinflammatory treatments may prevent, stabilize, or induce BV loss.
AB - Disease-modifying agents (DMAs), including interferon beta (IFNj3) and glatiramer acetate (GA), are the mainstays of long-term treatment of multiple sclerosis (MS). Other potent antiinflammatory agents like natalizumab and different types of chemotherapeutics are increasingly being used for treatment of MS, particularly in patients with breakthrough disease activity. Brain volume (BV) loss occurs early in the disease process, accelerates over time, and may be only partially affected by DMA therapy. Low-dose, low frequency IFN/3 administered once weekly and GA appear to partially reduce BV decline over the second and third years of treatment. High dose, high frequency IFN/3 demonstrated no clear effect on BV loss during this time period. Current evidence suggests that changes in BV after immunoablation may not be due entirely to the reso-ution of edema but may be related to potential chemotoxicity of high dose cyclophosphamide. Natalizumab reduces the development of BV decline in the second and third years of treatment. IV immunoglobulin showed a positive effect on decelerating BV reduction in relapsing and advanced stages of MS. These differences between DMAs may be explained by the extent of their therapeutic effects on inflammation and on the balance between inhibition or promotion of remy-elination and neuronal repair in the CNS. We described the mechanisms of action by which DMAs nduce accelerated, nontissue-related BV loss (pseudoatrophy) in the short term but, in the long run, may still potentially lead to permanent BV decline. The effects of corticosteroid therapy on changes in BV in patients with MS help clarify the mechanisms through which potent antiinflammatory treatments may prevent, stabilize, or induce BV loss.
UR - http://www.scopus.com/inward/record.url?scp=47549113346&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47549113346&partnerID=8YFLogxK
U2 - 10.1212/01.wnl.0000316810.01120.05
DO - 10.1212/01.wnl.0000316810.01120.05
M3 - Review article
C2 - 18606968
AN - SCOPUS:47549113346
SN - 0028-3878
VL - 71
SP - 136
EP - 144
JO - Neurology
JF - Neurology
IS - 2
ER -