New oral therapies show promise in MS

[kkmalaysia]

Two new oral therapies for multiple sclerosis may soon be available to those who suffer from the degenerative neurological condition.

The results of three studies published in the New England Journal of Medicine show that the drugs cladribine and fingolimod reduce relapse rates in people with relapsing-remitting multiple sclerosis (MS). [N Engl J Med 2010; 362(5): 416-26, N Engl J Med 2010; 362(5): 387-401, N Engl J Med 2010; 362(5): 402-15]

Oral therapies would be a welcome alternative for people with MS, for which current treatments involve frequent injections – sometimes daily – and intravenous infusions.

In an accompanying editorial, Dr. William Carroll, from the department of neurology at the Sir Charles Gairdner Hospital in Perth, Australia, wrote that easy administration would improve early treatment compliance for those with MS and improved drug efficacy would lead to better outcomes for patients. [N Engl J Med 2010; 362(5):456-8]

“Insights from these trials and others treating the initial stages of disease suggest that early direct targeting of the immune system offers the best hope for the prevention of later disability,” Carroll wrote.

An autoimmune disease, multiple sclerosis causes the body’s immune system to attack nerve cells and strip them of their protective myelin coating. Over time, nerve cells degrade and people with MS lose function at all levels, from vision and muscle control to memory.

Both cladribine and fingolimod act as immunosuppressants, staving off the autoimmune activity of MS by targeting inflammation. The drugs’ mechanisms are a departure from standard treatments – typically, interferon injections – which increase the body’s anti-inflammatory response.

Treatment with interferon is effective in preventing MS relapses, and there is data to suggest it
may prevent or ameliorate long term disability, said Dr. Kevin Tan, a consultant neurologist at the National Neuroscience Institute in Singapore.

However, the frequent dosing required with interferon and delivery in the form of injections can be a barrier towards adherence to early treatment.

The trials on cladribine and fingolimod, which included over 3,000 people with relapsing-remitting MS all showed annual relapse rates of less than 1 percent. Fingolimod was shown to slow disease progression and cladribine reduced disease activity. Overall, both drugs were shown to be more effective at preventing relapses compared to standard treatments as well as placebos.

“Early direct targeting of the immune system seems to be the most effective way of controlling MS at present,” Tan said.

All three trials were sponsored by the drug’s manufacturers. Novartis sponsored the fingolimod trials while Merck Serono sponsored the cladribine trial. Both companies are seeking US Food and Drug Administration approval for their products.

However, both Tan and Carroll pointed out that neither drug has been in trials long enough to determine what the long-term effects might be and there have been some negative side effects after use.

“We should be careful about extrapolating the long-term data of existing treatments to predict the effects of the newer oral treatments,” Tan said. “While the adverse effects of cladribine and fingolimod are generally low, serious and potentially life threatening effects still occurred rarely, [such as] herpes infection and cancers. Close postmarketing surveillance will be important to detect any increase in other unexpected adverse effects.”

Advances in oral therapy mean patients who are starting MS treatments for the first time can choose oral drugs as an alternative to existing therapy. Similarly, patients who are not responding well to current therapies now have more options for treatment.

However, Tan said it may not be necessary for patients who are responding well to their current medications with minimal side effects to discontinue their usual treatment in favor of beginning a new therapy.

Source: mims.com