Combination Therapy: The Future of Multiple Sclerosis Treatment
While taking more than one MS disease-modifying drug is currently rare, this may become more common in the future.
By Quinn Phillips
Medically Reviewed by Samuel Mackenzie, MD, PhD
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If you have multiple sclerosis (MS), chances are you’re taking a disease-modifying drug to slow the progression of your condition. These drugs — some of which are taken orally as pills, while others are injected or infused — are all immune modulators, changing the way the immune system acts.
Currently, each of these drugs is approved by the Food and Drug Administration (FDA) to be taken as the only disease-modifying drug for MS. But as more and more MS treatments have been developed in the last few years, an obvious question has come up: Could it be beneficial to take more than one of these treatments at the same time?
Very few studies have attempted to answer this question, and thus far, the results have been mixed. But some doctors and researchers are hopeful that taking more than one treatment to change the course of MS will ultimately prove beneficial and be widely adopted.
What the Studies Show
The most rigorous study to date of combined disease-modifying therapies is CombiRx, which looked at Copaxone (glatiramer) and Avonex (interferon beta-1a). Published in March 2013 in the journal,the study didn’t find any benefit from taking both drugs over taking the more effective single drug, Copaxone, by itself.
Bruce Bebo, executive vice president for research at the National Multiple Sclerosis Society, notes that CombiRx serves as an example for why other similar combination studies haven’t been carried out. “That was extremely expensive and time-consuming,” he says, adding that combination studies are “not trivial experiments to do.”
Another combination study, called SENTINEL, was published in March 2006 in.But that study — which looked at Tysabri (natalizumab) along with Avonex — only compared the combination with taking Avonex alone, so it’s unclear whether taking Tysabri alone could show the same benefit as the two drugs together, notes Mary Rensel, MD, a neurologist the Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research.
For a different sort of combination trial that showed a clear benefit, Dr. Rensel points to a study published in September 2009 in the Multiple Sclerosis Journal,which showed a reduction in MS lesions from adding the antibiotic minocycline to treatment with Copaxone.
In this study, doctors paired a disease-modifying drug with one approved for a completely different purpose, hoping that the addition of minocycline would enhance the efficacy of Copaxone. This is different, of course, from prescribing a second drug to treat MS symptoms, which Bebo notes is commonly done to help improve bladder control, reduce spasticity, or aid in walking.
Vitamin D, Biotin, and Statins
Dr. Rensel says that vitamin D is being widely studied as a promising disease-modifying treatment, possibly even as a primary or only disease-modifying drug. But since current research doesn’t support using it for this purpose, she currently just tries to optimize blood levels of vitamin D in her patients.
Bebo adds, “There is good evidence that low vitamin D levels are a risk factor for developing MS. The jury is still out on whether it will have any value as an intervention for ongoing disease.”
Despite the lack of evidence, says Bebo, some neurologists are recommending vitamin D supplementation since it’s relatively safe, and there’s a chance it might have some disease-modifying effects.
Another promising option, Rensel says, is biotin, also called vitamin B7, which holds particular promise for people with progressive forms of MS.
Statin drugs — normally prescribed to help regulate blood cholesterol levels — have also been studied for treating MS. But according to Rensel, that approach has seen setbacks because of the risk of intracerebral hemorrhage (bleeding in the brain) that comes with very low cholesterol levels.
Bebo notes that both biotin and statins have been tested as stand-alone drugs — not in combination with anything — for progressive forms of MS.
Looking to the Future
Rensel hopes that as new MS treatments are developed, there will be more research on combining treatments.
“What may happen with MS care is, if we have certain medicines to help with progression, and certain medicines to help with relapses, people would get combination treatment depending on their stage of MS,” she says.
Different treatments, Rensel says, could target neuroinflammation, neurodegeneration, and nerve fiber loss. Some nerve-repair studies, she notes, are ongoing, and others are being planned.
“Generally by the time people get to me, they’ve already had some nerve damage,” she says, so having a nerve-repair medicine to start people on right away would be an ideal option.
Bebo believes that given the progress in developing new MS treatments over the last two decades, “We’re ripe to do more trials comparing different treatment approaches. The landscape has changed so much in the last few years.”
This means studying not just combinations of drugs, he says, but individual drugs against one another to figure out which is best for a given situation.
“It’s a good problem to have, having all these agents,” Bebo says, adding that he expects future disease-modifying drugs to be even more effective and safer. And he thinks immune modulators may be paired with nerve-repair drugs within the next few years.
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