LONDON – 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.
Dr. Susana Otero-Romero
“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[12]: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).