November 29, 2002
By Adrian Burton
Special to DG News
A six-month course of intravenous cyclophosphamide administered once monthly is well tolerated and can provide dramatic benefits to patients with rapidly progressing multiple sclerosis (MS) who do not respond to standard immunomodulatory therapy.
Moreover, when returned to IMT treatment, therapeutic gains are maintained.
Rapidly progressing MS is associated with frequent relapses, poor recovery and poor response to IMT. "These patients are very hard to treat," explained Christina Caon, Neurology Research Coordinator at Wayne State University School of Medicine, in Detroit, Michigan, United States.
Zephir et al (Rev Neurol (Paris) 2002 Jan;158(1):65-9) recently showed that IV cyclophosphamide can have positive results in the short term treatment of progressive MS. "We now wanted to know what would happen in the longer term," said Dr. Caon, speaking here November 29 at the European Charcot Foundation Symposium.
The study enrolled 14 patients with rapidly progressive MS, defined as a three-point or greater increase in the Expanded Disability Status Score (EDSS) in the previous 12 months. All had received continuous IMT and multiple courses of IV methylprednisolone (IVMP) in the year prior to study entry.
All patients received a six-month course of IV cyclophosphamide, administered as one infusion per month at a starting dose of 1 g/m2 adjusted to achieve a white blood cell nadir of 2000-2500 two weeks after administration. IMT and IVMP regimens were stopped during the study period but IMT could be resumed after completion of the study regimen.
MRI brain scans with gadolinium were performed to detect lesions, eosinophils were counted to identify immune response deviation to the Th-2 type, and EDSS monitored throughout the 36 month follow-up period.
Magnetic resonance imaging scans were available for 11 patients. Nine patients had an increase in eosinophil counts -- 6 to 18 percent from baseline after two treatments with cyclophosphamide, but these remained elevated by 3 to 10 percent for the whole follow-up period. These nine patients also had reductions in brain atrophy as well as in gadolinium-enhancing lesions. The two patients who had no increase in eosinophil counts had less reduction in brain atrophy than the other patients and their gadolinium-enhancing lesions did not disappear.
During the six month course of cyclophosphamide treatment, EDSS scores decreased from a mean of 6.64 to 5.32. Importantly, improvement was maintained after patients switched back to IMT, with 36-month EDSS at a mean of 4.57. This finding is important, said Dr. Caon, because cyclophosphamide is an expensive therapy and infusions require patients spend a whole day at the clinic.
"The regimen was very well tolerated and these patients got dramatically better on cyclophosphamide," he commented. "Some were walking on their own again. One who was pretty much wheelchair-dependent could walk with a cane after six months of treatment."
"The message is that for people with rapidly progressive MS, cyclophosphamide
treatment may be beneficial and allow us to get them back on one of the
disease modifying therapies," Dr. Caon concluded.
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