Abstract
Immunomodulatory agent (IMA)-unresponsive multiple sclerosis (MS) can quickly evolve to a dramatic and irreversible disability. Treating these patients with appropriate immunosuppressive therapies can be a chance to arrest disease activity and progression. Cyclophosphamide (Cyc)-based intense immunosuppression has been successfully used to treat rapidly deteriorating, IMA-refractory MS patients. Therapeutic protocols combining Cyc and interferon beta (IFNβ) have also been successfully applied to treat IFNβ-unresponsive MS. The association of Cyc with other immunomodulatory drugs or monoclonal antibodies is currently being investigated in clinical trials aimed at treating severe forms of autoimmune diseases.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Kovarsky J (1983) Clinical pharmacology and toxicology of cyclophosphamide: emphasis on use in rheumatic diseases. Semin Arthritis Rheum 12:359–372
Boumpas DT, Austin HA 3rd, Fessler BJ et al (1995) Systemic lupus erythematosus: emerging concepts. Part 1: renal, neuropsychiatric, cardiovascular, pulmonary, and hematologic disease. Ann Intern Med 122:940–950
Brannagan TH 3rd, Pradhan A, Heiman-Patterson T et al (2002) Highdose cyclophosphamide without stem-cell rescue for refractory CIDP. Neurology 58:1856–1858
Gauthier SA, Weiner HL (2005) Cyclophosphamide therapy for MS. Int MS J 12:52–58
Perini P, Calabrese M, Rinaldi L, Gallo P (2007) The safety profile of cyclophosphamide in multiple sclerosis therapy. Expert Opin Drug Saf 6:183–190
Comabella M, Balashov K, Issazadeh et al (1998) Elevated interleukin-12 in progressive multiple sclerosis correlates with disease activity and is normalized by pulse cyclophosphamide therapy. J Clin Invest 102:671–678
Smith DR, Balashov KE, Hafler DA et al (1997) Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: increased interleukin-4 production and associated eosinophilia. Ann Neurol 42:313–318
Balashov KE, Smith DR, Khoury SJ et al (1997) Increased interleukin 12 production in progressive multiple sclerosis: induction by activated CD4+ T cells via CD40 ligand. Proc Natl Acad Sci U S A 94:599–603
Weiner HL (2004) Immunosuppressive treatment in multiple sclerosis. J Neurol Sci 223:1–11
Smith DR, Weinstock-Guttman B, Cohen JA et al (2005) A randomized blinded trial of combination therapy with cyclophosphamide in patients-with active multiple sclerosis on interferon beta. Mult Scler 11:573–582
Patti F, Reggio E, Palermo F et al (2004) Stabilization of rapidly worsening multiple sclerosis for 36 months in patients treated with interferon beta plus cyclophosphamide followed by interferon beta. J Neurol 251:1502–1506
Patti F, Cataldi ML, Nicoletti F et al (2001) Combination of cyclophosphamide and interferon-beta halts progression in patients with rapidly transitional multiple sclerosis. J Neurol Neurosurg Psychiatry 71:404–407
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Perini, P., Calabrese, M., Rinaldi, L. et al. Cyclophosphamide-based combination therapies for autoimmunity. Neurol Sci 29 (Suppl 2), 233–234 (2008). https://doi.org/10.1007/s10072-008-0947-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10072-008-0947-9