AT ECTRIMS 2016
LONDON (FRONTLINE MEDICAL NEWS) – New European guidelines on the pharmacologic treatment of multiple sclerosis consider all types of adult patients, including those with clinically isolated syndrome.
In addition to advocating early treatment in clinically isolated syndrome (CIS), the guidelines look at the treatment of relapsing-remitting multiple sclerosis (RRMS) and primary progressive MS (PPMS), and give recommendations on monitoring therapy, what to do if a treatment needs to be stopped or switched, and how to treat in special situations such as pregnancy.
Developed jointly by the European Committee for Treatment and Research in Multiple Sclerosis ( ECTRIMS ) and the European Academy of Neurology ( EAN ), the guidelines are the first to formalize how best to use new disease-modifying drugs and strategies in Europe, based on current evidence.
“With several new drugs available in the past years, and others soon to come, this poses a major challenge to advice on a specific treatment for a specific patient,” said Susana Otero-Romero, MD , of the Centre d’Esclerosi Múltiple de Catalunya ( CEMCAT ) at Vall d’Hebron University Hospital in Barcelona.
Dr. Otero-Romero, who presented some general recommendations from the draft guidelines at the ECTRIMS annual congress, added that evidence-based guidance was needed and so ECTRIMS and EAN convened an expert panel in 2015 to review available data. The focus was on disease-modifying therapies approved by the European Medicines Agency.
The expert panel was chaired by the president of ECTRIMS, Xavier Montalbán, MD , of CEMCAT, and Ralf Gold, MD , of Ruhr-Universität Bochum in Germany, on behalf of the EAN, and included MS experts from across Europe, as well as patient representatives from groups such as the Multiple Sclerosis International Federation and the European Multiple Sclerosis Platform .
The panel followed the EAN’s recently issued framework for developing guidelines ( Eur J Neurol. 2015 Dec;22:1505-10 ) and Dr. Otero-Romero emphasized that the guidelines were built on the evidence base, using GRADE ( Grading of Recommendations Assessment, Development Evaluation ) methodology, to rate the quality and strength of each recommendation. Where no evidence was found, expert consensus was used.
Dr. Otero-Romero noted that an overall recommendation was that “the entire spectrum of disease-modifying drugs should only be prescribed in centers where there was the infrastructure to provide the proper monitoring of patients, comprehensive assessment, and detection of side effects and how to address them.”
That doesn’t mean patients need to be treated in specialist centers, Dr. Montalbán was keen to point out during discussions. It means that centers who prescribe the expanding range of MS drugs need to have a process to enable them to take good care of patients, monitor them, be aware of side effects, and have the expertise to be able to manage patients if side effects do occur.
“We looked specifically at the subpopulation of patients with CIS,” Dr. Otero-Romero noted, and said the panel decided that treatment with interferon or glatiramer acetate was the best option for CIS patients with an abnormal MRI scan who do not fulfill MS diagnostic criteria.
During discussion, a delegate queried why only injectable drugs were recommended when patients in this early phase of disease would probably be asking for oral treatment. Dr. Otero-Romero responded that this recommendation was based purely on the evidence available. “For now, this would only support starting on interferon or glatiramer acetate,” she said.
For patients with RRMS, defined as multiple relapses, MRI activity, or both, the recommendation is to offer early treatment with disease-modifying drugs. Which drug should be used is not specified, although the guidelines provide general advice on factors to consider when choosing a drug, including patient characteristics and comorbidities, disease severity and activity, the drug’s safety profile, and accessibility to the drug.
“There have not really been any head-to-head comparisons between drugs, so we do not have enough evidence to recommend one over another,” Dr. Otero-Romero said. “If you do not have good evidence you cannot really stratify the drugs and say ‘this one goes first, this one goes second,’ so we still need more evidence.”
For monitoring, consider MRI together with clinical measures. A reference brain MRI, taken within 6 months of starting disease-modifying treatment, is advocated, with a follow-up brain scan at 1 year, although the timing will need to be adjusted based on the drug treatment being used and the level of disease activity.
If there is a poor response to interferon or glatiramer acetate therapy or there is evidence of disease activity, the recommendation is to offer a more efficacious drug. If a highly efficacious drug then needs to be stopped for any reason, another highly efficacious drug should be considered. Factors to consider when switching include the degree of disease activity, which dictates how quickly the switch needs to be made, drugs’ respective half-lives and biological activity, and the potential for rebounding disease activity, particularly with natalizumab (Tysabri).
Although the expert panel has included a recommendation on the use of ocrelizumab for PPMS based on available phase III trial data, this is only if the drug is licensed for use by the EMA by the time the guidelines are published.
“We have agreed on our first set of recommendations. We will probably still work to refine some of these, and we expect to publish at the beginning of next year,” Dr. Otero-Romero said.
Providing independent comment in an interview, Samuel F. Hunter, MD , of the Advanced Neurosciences Institute in Nashville, Tenn., said that the European guidelines were of interest as there were no up-to-date guidelines on drug therapy for MS available in the United States.
While the American Academy of Neurology has produced practice guidelines on the use of disease-modifying therapies in MS ( Neurology. 2002;58:169-78 ) and issued specific guidance on natalizumab ( Neurology. 2008;71:766–73 ), these documents were published years ago. Five new therapies have appeared since then, Dr. Hunter said.
“Guidance is so far behind the advancement of therapy for MS, such that we don’t have any accepted guidelines. The current opinion from various groups is that all therapies should be available for all patients, according to physician advice,” Dr. Hunter said.
“People predominantly follow individual escalation of therapy efficacy guideline for the majority of patients, and people with very severe, fulminant relapses are relegated to higher-efficacy therapies,” he added.
The new European guidelines will influence what is happening in the United States, Dr. Hunter said, but there is such a diversity of interests among the large managed care organizations, the government, payers, pharmaceutical companies, and different academic centers, for example, that reaching a consensus will be difficult.
Dr. Otero-Romero did not declare any specific disclosures in relation to her presentation of the guidelines. Dr. Hunter did not have any disclosure relevant to his comments.