A well-known MS medication is showing promise for people with more aggressive forms of the disease who haven't responded well to other treatments, according to a group of physicians in the UK.
The researchers who analyzed the effectiveness of the drug Copaxone (glatiramer acetate) for people with aggressive relapsing-remitting multiple sclerosis say an observational analysis performed at their clinic strongly suggests the medication may be beneficial for these patients. Results of the analysis were released at the American Academy of Neurology annual meeting last month.1
Relapsing MS is the most common form of the disease, affecting as much as 85 percent of people who've been diagnosed. Contrasting with the primary-progressive and secondary-progressive forms, relapsing MS is characterized by clearly delineated flare-ups followed by episodes of acute worsening of neurologic function. These are followed by periods of complete or partial recovery.2
'Encouraging' Results for People with Severe MS
"Our significant findings are very encouraging for patients who have severe, active forms of relapsing-remitting MS," explained Michael Boggild, MD, who headed the evaluation. He said this retrospective analysis was an informal observation of Copaxone's efficacy in his clinical practice. Based on the positive outcome, he and his colleagues have initiated a more formal clinical trial of the drug.
Copaxone is currently approved as a medicine to reduce the frequency of relapses, or exacerbations, in people with relapsing multiple sclerosis. The drug has also been shown to reduce the number of brain lesions associated with MS.3 Copaxone was tested in this analysis in a group of patients who had not responded well to interferon therapy, nor who were able to maintain a long-term regimen of another MS drug, Novantrone (mitoxantrone). The latter belongs to a class of medications known as antineoplastics (ann-tee-nee-oh-PLAS-tiks). Prescribed as a cancer therapy, it is also indicated as a treatment for MS and is designed to extend the time between relapses.
Limited Efficacy
Nonetheless, "the benefits of this agent [Novantrone] in reducing disease progression and relapse rate cannot be sustained in the long-term, as treatment is limited by the potential for cumulative cardiotoxicity [heart damage]," wrote Boggild, a consultant neurologist at the Walton Centre in Liverpool, UK, and his research team.
As such, the investigators had been searching for another potential treatment for their patients with aggressive relapsing MS who had few other options, Boggild explained, in a telephone interview.
For their open-label, observational analysis, Boggild, and his fellow investigators had followed 27 patients. Each was coming to the end of Novantone monotherapy with the aim of reducing the risk of heart damage. At that point, the patients were given the combination of Copaxone and Novantrone for up to 7 months, then eventually weaned off Novantrone using Copaxone monotherapy for the remaining 5 years. "It was a stepwise switch," Boggild explained.
Each patient was then followed during the observational study. Measures of the number of relapses, as well as each patient's level of disability, were calculated in this follow-up period. In nine patients, magnetic resonance imaging (MRI) scans were begun to determine the medications' effect on brain lesions.
Positive Outcome
During the follow-up period, the researchers found positive results. "We were pleasantly surprised that these patients … actually seemed, overall, better than they had been," Boggild said. "They were certainly not firing up again as far as their disease was concerned and generally were tolerating Copaxone well."
The researchers found that Copaxone stabilized or improved disability and significantly suppressed the number of brain lesions. No new lesions have been seen on MRI scans, as well, Boggild and his colleagues reported. While on Novantrone alone, the investigators had discovered six relapses in the patients. But only two relapses happened several months after Copaxone monotherapy was started.
After an average of nearly 3 years on Copaxone monotherapy, there were no reports of relapses, and at the most recent follow-up exams, disability measures of each patient were either stable or had improved, the study team found.
Last year, initial trial results of the first 10 patients were unveiled at a meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Vienna, Austria. No relapses had been reported in any of these patients at an average of 30 months after starting treatment with Copaxone monotherapy. While the patients initially had disability severe enough to prevent them from taking part in full daily activities, they had only mild disability after 30 months on the medication, the investigators had reported.
"It may just be luck," Boggild said, of the latest findings. "But I'm beginning to think, personally, that there's something synergistic about the two drugs."
A Therapeutic Synergy?
What underlies that synergistic effect isn't yet known, but is the subject of ongoing in-vitro studies, Boggild stated, adding that he is "excited about this combination." He added that in 10 years as a clinician, he hasn't promising results with any other combination of medications.
The stepwise-switch protocol may not necessarily be suitable for all patients. Boggild says physicians typically integrate a range of diagnostic evaluations in individual cases to gather the larger perspective about how a person's disease is progressing. Treatment is then prescribed based on that evaluation. For instance, in his practice, Boggild says Novantrone is typically prescribed for those who have failed first-line treatment or as first-line therapy for those with more aggressive forms of MS.
Thus, the unique way this combination works "may make it a logical choice … for patients with particularly aggressive forms of the disease," Boggild added.
Based on the positive findings, Boggild's group hopes to recruit up to 100 patients for a more formal, randomized, controlled clinical trial to test the combination of Copaxone/Novantrone against a group of patients taking interferon therapy, he said.
"I’m encouraged that further ongoing studies may validate our results," he said.
1. Ramtahal, J, Jacob A, Das K, Boggild M. 5-year retrospective study of the use of mitoxantrone and glatiramer acetate combination in patients with very active relapsing remitting multiple sclerosis. American Academy of Neurology 57th Annual Meeting. 2005 Apr 9-16. Miami Beach, FL.
2. National Multiple Sclerosis Society. What is Multiple Sclerosis? Available at: http://www.nationalmssociety.org/What%20is%20MS.asp. Accessed April 29, 2005.
3. Teva Pharmaceutical Industries. About Copaxone. Available at: http://www.mswatch.com/therapy/section.aspx?SectionId=789eabf5-3a07-4dff-a7ee-0d4ad1381a6d. Accessed April 29, 2005.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
