Final Results: Rescue Therapy With High Dose Intravenous Methotrexate With Leucovorin Rescue (HDIV-MTX) in Multiple Sclerosis Patients Worsening Despite Avonex(R) Therapy
May 6, 2004
Source: MidAmerica Neuroscience Research Foundation
The MidAmerica Neuroscience Research Foundation, which has been studying the intravenous use of the chemotherapy drug methotrexate to treat multiple sclerosis (MS), presented final results of its most recent study at the American Academy of Neurology's annual meeting April 28.
Researchers believe an inflammatory immune response to myelin antigens plays a major role in the pathogenesis of early MS lesions. The Foundation is studying the safety and effectiveness of methotrexate (HDIV-MTX) in treating progressive MS. Methotrexate is an s-phase, chemotherapeutic anti-metabolite used in the treatment of various neoplasms, particularly CNS lymphoma. MTX can be given intravenously in high enough doses to cross the blood-brain barrier (BBB) and enter the CNS without BBB disruption. The effect on peripheral normal tissues can be rescued by Leucovorin (folinic acid), which does not enter the brain.
"In MS, by repeating the high dose intravenous injection of MTX with leucovorin rescue at regular intervals, the autoimmune response and inflammation in the brain is suppressed," Dr. Vernon Rowe, founder of the foundation, said. "Final analysis of the most recent study shows repeated treatment at regular intervals may prevent a significant repopulation of the CNS by immune elements from the periphery."
The study involved 15 patients who were worsening despite weekly IFNB-1a therapy. The open label versus baseline study used bimonthly HDIV-MTX in combination with IFNB-1a therapy.
The results of the Multiple Sclerosis Functional Composite Test (MSFC) show clinically significant improvements in the composite scores and two of the subsets. Seven percent worsened, seven percent remained stable and eighty-six percent improved during one year of treatment, even though all had been worsening on IFNB-1a before the first HDIV-MTX treatment. The results suggest that bimonthly treatments with HDIV-MTX combined with weekly IFNB-1a therapy is effective in stopping the clinical progression in patients who are worsening on IFNB-1a therapy.
Rowe said the Foundation hopes to conduct a multi-center clinical trial
of the treatment.
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