Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2
Abstract
There is evidence that treatment with an antibody to tumor necrosis factor alpha (TNF alpha) improves an animal model of multiple sclerosis (MS) and is beneficial in two systemic inflammatory diseases in humans, but there are no reports about anti-TNF treatment of MS. Therefore, we treated two rapidly progressive MS patients with intravenous infusions of a humanized mouse monoclonal anti-TNF antibody (cA2) in an open-label phase I safety trial and monitored their clinical status, gadolinium-enhanced brain magnetic resonance imaging (MRI), and peripheral blood and cerebrospinal fluid (CSF) immunologic status.
We did not notice any clinically significant neurologic changes in either patient.The number of gadolinium-enhancing lesions increased transiently after each treatment in both patients. CSF leukocyte counts and IgG index increased after each treatment.
The transient increase in the number of gadolinium-enhancing lesions that followed each infusion of cA2 together with the increase in cells and immunoglobulin in the CSF of each patient suggest that the treatment caused immune activation and an increase in disease activity. These results suggest that further use of cA2 in MS is not warranted and that studies of other agents that antagonize TNF alpha should be carried out with frequent monitoring of gadolinium-enhanced MRIs.
NEUROLOGY 1996;47: 1531-1534
Get full access to this article
View all available purchase options and get full access to this article.
REFERENCES
1.
Beck J, Rondot P, Catinot L, et al. Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: do cytokines trigger off exacerbations? Acta Neurol Scand 1988;78:318-323.
2.
Rieckmann P, Albrecht M, Kitze B, et al. Cytokine mRNA levels in mononuclear blood cells from patients with multiple sclerosis. Neurology 1994;44:1523-1526.
3.
Rieckmann P, Albrecht M, Kitze B, et al. Tumor necrosis factor-alpha messenger RNA expression in patients with relapsing-remitting multiple sclerosis is associated with disease activity. Ann Neurol 1995;37:82-88.
4.
Cannella B, Raine CS. The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol 1995;37:424-435.
5.
Selmaj K, Raine CS, Cannella B, Brosnan CF. Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. J Clin Invest 1991;87:949-954.
6.
Robbins DS, Shirazi Y, Drysdale BE, et al. Production of cytotoxic factor for oligodendrocytes by stimulated astrocytes. J Immunol 1987;139:2593-2600.
7.
Selmaj K, Raine CS. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 1988;23:339-346.
8.
Kuroda Y, Shimamoto Y. Human tumor necrosis factor-alpha augments experimental allergic encephalomyelitis in rats. J Neuroimmunol 1991;34:159-164.
9.
Nataf S, Louboutin JP, Chabannes D, et al. Pentoxifylline inhibits experimental allergic encephalomyelitis. Acta Neurol Scand 1993;88:97-99.
10.
Rott O, Cash E, Fleischer B. Phosphodiesterase inhibitor pentoxifylline, a selective inhibitor of T helper 1- but not type 2-associated lymphokine production, prevents induction of experimental allergic encephalomyelitis in Lewis rats. Eur J Immunol 1993;23:1745-1751.
11.
Monastra G, Cross AH, Bruni A, Raine CS. Phosphatidylserine, a putative inhibitor of tumor necrosis factor, prevents autoimmune demyelination. Neurology 1994;43:153-163.
12.
Ruddle NH, Bergman CM, McGrath KM, et al. An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. J Exp Med 1990;172:1193-1200.
13.
Selmaj K, Raine CS, Cross AH. Anti-tumor necrosis factor therapy abrogates autoimmune demyelination. Ann Neurol 1991;30:694-700.
14.
Baker D, Butler D, Scallon BJ, et al. Control of established experimental allergic encephalomyelitis by inhibition of tumor necrosis factor (TNF) activity within the central nervous system using monoclonal antibodies and TNF receptor-immunoglobulin fusion proteins. Eur J Immunol 1994;24:2040-2048.
15.
Genain CP, Roberts T, Davis RL, et al. Prevention of autoimmune demyelination in non-human primates by a cAMP-specific phosphodiesterase inhibitor. Proc Natl Acad Sci USA 1995;92:3601-3605.
16.
Derkx B, Taminiau J, Radema S, et al. Tumor-necrosis-factor antibody treatment in Crohn's disease. Lancet 1994;342:173-174.
17.
Van Dullemen HM, Van Deventer SJH, Hommes DW, et al. Treatment of Crohn's disease with anti tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology 1995;109:129-135.
18.
Elliott MJ, Maini RN, Feldmann M, et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumor necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 1994;344:1105-1110.
19.
Elliott MJ, Maini RN, Feldmann M, et al. Repeated therapy with monoclonal antibody to tumor necrosis factor alpha (cA2) in patients with rheumatoid arthritis. Lancet 1994;344:1125-1127.
20.
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1444-1452.
21.
Barkhof F, Scheltens P, Frequin STFM, et al. Relapsing-remitting multiple sclerosis: sequential enhanced MR imaging vs. clinical findings in determining disease activity. AJR 1992;19:1041-1047.
22.
Hartung HP, Reiners K, Archelos JJ, et al. Circulating adhesion molecules and tumor necrosis factor receptor in multiple sclerosis: correlation with magnetic resonance imaging. Ann Neurol 1995;38:186-193.
23.
van Oosten BW, Rep MHG, van Lier RAW, et al. A pilot study investigating the effects of orally administered pentoxifylline on selected immune variables in patients with multiple sclerosis. J Neuroimmunol 1996;66:49-55.
24.
Stone LA, Frank JA, Albert PS, et al. The effect of interferon-beta on blood-brain barrier disruptions demonstrated by contrast enhanced magnetic resonance imaging in relapsing-remitting multiple sclerosis. Ann Neurol 1995;37:611-619.
Information & Authors
Information
Published In
Copyright
Copyright 1996 by Advanstar Communications Inc.
Publication History
Published online: December 1, 1996
Published in print: December 1996
Authors
Metrics & Citations
Metrics
Citations
Download Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.
Cited By
- Tumor Necrosis Factor-alpha Inhibitors: Can They Induce an Idiopathic Inflammatory Demyelinating Disease in the Central Nervous System?, Journal of Multiple Sclerosis Research, (2024).https://doi.org/10.4274/jmsr.galenos.2024.2024-3-1
- Oligodendrocytes in central nervous system diseases: the effect of cytokine regulation, Neural Regeneration Research, (2024).https://doi.org/10.4103/1673-5374.392854
- The contribution of tumor necrosis factor to multiple sclerosis: a possible role in progression independent of relapse?, Journal of Neuroinflammation, 21, 1, (2024).https://doi.org/10.1186/s12974-024-03193-6
- Management of Uveitis Patients on Anti-TNF Agents Who Develop Demyelinating Disease – A Case Series, Journal of Ophthalmic Inflammation and Infection, 14, 1, (2024).https://doi.org/10.1186/s12348-024-00403-3
- Ophthalmological and Neurological Findings in Patients with Idiopathic Uveitis Associated with Retinal Vasculitis and the Relation with the HLA DR15 Allele, Ocular Immunology and Inflammation, (1-7), (2024).https://doi.org/10.1080/09273948.2024.2316759
- Transcriptomics identifies blunted immunomodulatory effects of vitamin D in people with multiple sclerosis, Scientific Reports, 14, 1, (2024).https://doi.org/10.1038/s41598-024-51779-0
- Targeting cytokine networks in neuroinflammatory diseases, Nature Reviews Drug Discovery, (2024).https://doi.org/10.1038/s41573-024-01026-y
- The dichotomic role of single cytokines: Fine-tuning immune responses, Cytokine, 173, (156408), (2024).https://doi.org/10.1016/j.cyto.2023.156408
- Are 5HT7 Receptors Possible Target for Multiple Sclerosis?, Research Journal of Pharmacy and Technology, (1514-1520), (2023).https://doi.org/10.52711/0974-360X.2023.00248
- Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy, Journal of Clinical Medicine, 12, 4, (1630), (2023).https://doi.org/10.3390/jcm12041630
- See more
Loading...
View Options
Get Access
Login options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.
If you need immediate support or to place an order, please call or email customer service:
- 1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
- 1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
- [email protected]
We appreciate your patience during this time and apologize for any inconvenience.