STOCKHOLM—With multiple choices for the treatment of multiple sclerosis (MS) available, the question is where does one start? That question was unanswered here at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis following a debate on whether to charge ahead with the most potent therapy or go with solid treatment that can be escalated later if there is a disease breakthrough.
The use of highly potent disease modifying agents upfront—an attempt to induce remission—appears successful in a high percentage of MS patients and should be the path taken, suggested Alasdair Coles, MBChB, PhD, professor of neurology at Cambridge University in the United Kingdom.
That policy might be exposing patients to increased risks of infection—without any guarantees that the induction therapy will prevent the disease from reappearing down the road, so a policy of escalating treatment as needed should remain the therapy of choice, argued Emmanuelle Waubant, MD, PhD, FAAN, professor of neurology at the Weill Institute for Neurosciences at the University of California, San Francisco.
During the debate, Dr. Coles cited studies that show early treatment with alemtuzumab—one of three induction therapies in MS aside from autologous hematopoietic stem cell therapy and treatment with cladribine—was able to induce long-lasting disease suppression.
"Can an induction therapy lead to long-lasting disease suppression with a restricted window of risk? Is this better than continuous dosing with escalation?" he asked rhetorically and then answered with studies that have been performed using alemtuzumab.
He cited a phase 2 study of 60 MS patients followed for 12 years. One-third of the patients received two cycles of alemtuzumab at baseline and year one and didn't need any other treatment; another 38 percent of patients required an additional booster of alemtuzumab during their 12-year follow-up, and 29 percent of the patients required two or more alemtuzumab therapies. The annualized relapse rate in that cohort was less than one percent.
In larger pivotal trials, Dr. Coles illustrated that treatment with alemtuzumab compared with interferon therapy had similar outcomes, with about 50 percent of the alemtuzumab patients being free of relapses over the nine-year course of follow-up.
He said that with alemtuzumab therapy there was a risk of serious infection that persisted during the time that alemtuzumab was being administered; that patients were advised against pregnancy for about three years, and the cone of the risk of autoimmunity extended for four years, and those risks were repeated if there was the need for another treatment cycle.
Dr. Coles acknowledged that there wasn't likely to be a perfect induction therapy any time soon, but he thought that patients would trade off 11 days of therapy for years of freedom from progressive MS.
Taking a different position, Dr. Waubant said that if induction isn't always successful, and it exposes patients to harm from infection and autoimmunity for long periods of time, it isn't ready for prime time. "True induction therapy with long-term safety and efficacy data are not yet available," she argued.
"The lack of long-term follow-up means we really don't know what this treatment strategy does, most of these studies are small, they weren't always randomized, and have focused on the early impacts and not on the long-term impacts after discontinuing treatment," she said.
On the other hand, Dr. Waubant said, "Early traditional disease-modifying therapy initiation is effective and safe for most patients with clinically isolated syndromes or relapsing-remitting multiple sclerosis."
She said that treatment escalation has shown that it will prevent patients from moving to secondary progressive MS, can save money, prolongs quality adjusted survival, and was no different in preventing increase in disability when compared to early intensive therapy.
Dr. Waubant suggested that patients with early MS be monitored carefully clinically and with yearly MRI and then most to early escalation if warranted.
Dr. Coles disclosed relevant relationships with BTG, Millennium, Ilex, Genzyme, and Sanofi. Dr. Waubant disclosed relevant relationships with Novartis, Roche, Biogen, Jazz Pharmaceuticals, Emerald, and DBV.
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ECTRIMS Abstract 301: Waubant E. Why escalation therapy is the preferred principle over treatment induction.