Susan Jeffrey

September 12, 2014

BOSTON — A new survey of US neurologists shows good overall consensus on management approaches to patients with clinically isolated syndrome (CIS), radiologically isolated syndrome (RIS), and relapsing-remitting multiple sclerosis (RRMS).

For example, 100% of respondents would recommend a disease-modifying therapy, but there was little consensus on which of these drugs to use given what is now a wide variety of choices, noted lead author Carlo Tornatore, MD, Department of Neurology, Georgetown University, Washington, DC.

On the basis of these findings, Dr. Tornatore said, "we were able to make a treatment practice guideline or kind of a consensus of what people do, and we think this has value. Neurologists who take care of MS patients are going to be asked for quality measures for their care of those patients by CMS [Centers for Medicaid & Medicare Services], and they're going to want to know are we offering quality care to our patients."

Their findings were presented here at MS Boston 2014, the 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS) meeting. The study was funded by Biogen Idec.

Dr. Carlo Tornatore

Finding Consensus

A "robust and up-to-date treatment algorithm for MS based on Class I evidence has not been established," the researchers write. The purpose of this project was to understand what consensus standards are for neurologists in the United States in the treatment of RIS, CIS, and RRMS. They used a case-based survey, asking how neurologists would manage 3 hypothetical patients with 1 of these conditions.

The surveys were sent to 239 members of the Consortium of MS Centers, Dr. Tornatore said. "That's pretty much their whole group, and half of them responded," Dr. Tornatore said. "We had 107 responses back from all over the country and they represent probably half of all the MS patients being treated in the United States." Surveys were completed online and were anonymous to the steering committee.

The goal was to find out where there is consensus in terms of diagnosing and treating patients with any of these 3 conditions. "We set our bar high," he noted. "We said 75% of respondents would have to agree on a certain point." A shorter second survey was used to further clarify responses from the first survey when no consensus was obtained and was completed by 103 of the 107 respondents, the authors note.

In the end, there were 47 points in all, reflecting a greater than 75% consensus in practice patterns. The results showed a trend toward earlier, more aggressive treatment.

For instance, in the case of a 25-year-old who was recently diagnosed with relapsing-remitting MS, Dr. Tornatore said, "the question was would you treat that patient with a disease-modifying drug, and 100% of the people said yes, which is great. And then the question was well, what would you treat them with, and there was no consensus."

Consensus was seen again when 97% said they would follow up with MRI within 1 year, and 75% said they would do the MRI within 6 months.

In clinically isolated syndrome, the question was, after a patient has had 1 clinical event, at what point would the neurologist elect to give treatment? "Well, 100% said if the brain MRI was normal they would not treat," he said. "If the patient had 1 or more nonenhancing lesions they would go ahead and treat: over 90% would then treat. And interesting data about not doing a spinal tap – only 15% would do a spinal tap in somebody who has clinically isolated syndrome and a gadolinium-enhancing lesion."

In terms of treatment for a patient newly diagnosed with MS, there was no consensus on which drug to use. Dr. Tornatore said this is to be expected with the recent surge in treatment choices; the responses were split between injectable medications, new oral agents, or intravenous natalizumab. The only point of consensus on treatment was in the patient who had very active disease and was negative for JC virus antibody; most respondents would choose to offer the patient natalizumab.

On the basis of the points of consensus, the authors were able to derive a practice guideline grounded in what neurologists are already doing, he said.

The algorithm is as follows:


  • Treat if the patient has more than 2 new gadolinium-enhancing lesions (80%)

  • Follow-up MRI within 12 months (84%)


  • Initiate treatment if patient has more than 2 nonenhancing T2 lesions (93%) or 1 gadolinium-enhancing lesion in addition to nonenhancing T2 lesions (98%)

  • Follow-up MRI within 12 months (75%)


  • Treat mild disease with injectable treatment (38%) or dimethyl fumarate (30%) with follow-up MRI within 12 months (97%)

  • Consider switching to an oral or intravenous disease-modifying therapy if the patient has 2 or more new T2 lesions (67%) or more than 1 new gadolinium-enhancing lesion (52%) while receiving therapy.

  • If the patient is JC virus negative and has aggressive disease, treat with natalizumab (89%), with follow-up MRI within 12 months (97%)

"We're trying to start to tease out what the best practices are," he said. "Again, the point here was not to pick particular drugs but the important thing was to pick out certain things that are standard of care, that all of us would agree are useful to do — they're part of our 'right now.' They're not going to be onerous new things to meet this quality measure."

"These compelling findings show considerable conformity in treatment practices among US physicians, who are adopting a more aggressive approach to early treatment of MS, although variations in therapy selections are potentially influenced by payer formulary coverage," the authors conclude. "The completed consensus guidelines may offer key insights into harmonizing MS care without increasing overall healthcare cost."

The next step is to bring the guideline to the MS Section of the American Academy of Neurology for feedback, then perhaps to the National Quality Forum, an organization that reviews and endorses measures of quality health care, and ultimately to CMS, he said. "We all feel that these are very reasonable, and that would actually not only be a good quality measure, but would also educate somebody who doesn't take care of a lot of MS patients, but could use it as a guideline for what they're doing."

This is the second such survey this group has done. The first was carried out in 2011 and published in Neurology Clinical Practice in March 2012.

In that previous report, 87% of respondents recommended initiation of disease-modifying therapy in patients with CIS with MRI brain lesions. An injectable disease-modifying therapy was recommended by 90% to 98% for treatment-naive patients with mild relapsing MS. There was 97% consensus to treat highly active disease, but still at that time no consensus on therapy choice.

For RIS, there was consensus not to initiate treatment with brain but not spinal MRI lesions. "Current US treatment patterns emphasize MRI in MS diagnosis and subsequent treatment decisions, treatment of early disease, aggressive initial treatment of highly active MS, and close patient monitoring."

"Fifty people who took the first survey took it again, and what was striking is things were pretty much the same from over a 3-year period," Dr. Tornatore noted. "The thing that changed is we have different drugs. Four years ago if somebody was started on a medication it was usually injectable. Now, there's no consensus — it could be injectable, it could be an oral drug, it could be an IV [intravenous] medication, so no consensus on that but because we have more drugs that's what you would expect."

The study was funded by Biogen Idec. Dr. Tornatore reports receiving grant support and serving on an advisory council and speakers' bureau for Biogen Idec, a speakers' bureau for Teva, and an advisory council for Novartis.

MS Boston 2014, the 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS) meeting. Poster 295. Presented September 11, 2014.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.