April 3, 2003
Medscape Medical News
Campath-1H (alemtuzumab) virtually stops episodes and decreases the disability of early-stage multiple sclerosis (MS), according to a small open-label study.
The effect is only seen when the drug, a humanized monoclonal antibody that depletes T cells, is given in the early relapsing-remitting stage of the disease, Alastair Compston, PhD, FRCP, chairman of the department of neurology, Cambridge University, U.K., told attendees of the American Academy of Neurology 55th annual meeting, "when clinical disease activity is attributable to inflammation."
In an open-label study of the drug, Dr. Compston compared use of Campath-1H in two groups of patients: 36 patients with the secondary progressive phase of the disease, with a mean of 12 years since onset of disease and and four years since onset of progression; and 22 patients who had the disease for a mean of 2.7 years prior to treatment and none of whom were in the progressive phase.
Both groups of patients had been given 24 mg of the drug per day for five days, for a total dose of 120 mg, and followed for about two years.
The relapse rate of the secondary progressive MS group remained suppressed during a mean of seven years of follow-up but their disability continued to progress. There were no significant infective adverse effects, but one third of patients developed Graves' disease.
In comparison, before treatment, the relapsing-remitting group had a mean of three episodes a year and their Expanded Disability Status Scale (EDSS) had increased by 2.4 points. After treatment, the mean relapse rate was 0.1 per year, and one patient relapsed after a subsequent follow-up of a mean of 13 months. The EDSS was 0.5 points less disabled than before treatment for this group.
Dr. Comptom is convinced of the benefit of the medication. "What is persuasive is everybody goes in the right direction," he told Medscape. "You can more or less eliminate episodes," but he said, "You [have] to treat it early and aggressively."
Adverse effects included hives and elevated temperature upon administration. Nonsteroidal anti-inflammatory drugs resolved this, he said. And a dose of steroids can prevent the temporary increase in symptoms experienced by some patients.
The main concern, Dr. Compston said, was that 27% of the patients developed autoimmune thyroid disease. This resolved in all but one of 15 patients by detecting the disease at a preclinical stage, and early treatment. In most patients it disappeared, but it remains a medical problem for the one patient. No patients experienced any serious infections.
"The critical therapeutic issue [now] is whether this will slow or prevent axonal degeneration and sustained accumulation of disability," write Dr. Compston and colleagues in their abstract.
Researchers are focusing on that subject in a head-to-head trial comparing two doses of Campath-1H with a 44 µg of Rebif (interferon beta-1a). This multicenter trial taking place in Europe and the U.S. began in December 2002. The treatment phase will last three years and observations will last five years. Sustained accumulation of disability is the outcome measure.
Stephen Reingold, MD, vice president of medical research for the National Multiple Sclerosis Society, who heard the presentation, agreed these results had not been seen with other drugs. But, he told Medscape in an interview, it will need rigorous studies to determine "if it's real" in other patient groups as well, to determine definitively that the effect is a function of the drug rather than the natural course of the disease.
Also, he was concerned about the nearly 30% of patients who developed thyroid disease, and whether that truly resolves, another question he hopes will be answered by the larger trial.
Campath, manufactured by Ilex Pharmaceuticals and distributed by Berlex, is approved by the U.S. Food and Drug Administration for the treatment of B-cell chronic lymphocytic leukemia in patients who have been treated with alkylating agents and who have failed fludarabine therapy.
The study was supported by Wellcome Trust, the Multiple Sclerosis Society (U.K.), and Ilex Oncology.
AAN 55th Annual Meeting: Abstract S21.005. Presented April 1, 2003.
Reviewed by Gary D. Vogin, MD
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