Literature Review

ECTRIMS and EAN Publish Recommendations for Treating MS


The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have published a guideline to offer up-to-date, evidence-based recommendations for the treatment of adult patients with MS. The guideline is intended to fill a perceived need for a comprehensive document that includes information about recently approved MS therapies and helps clinicians and patients resolve difficulties in everyday clinical practice. It was published in the February issue of Multiple Sclerosis.

Authors Addressed 10 Questions

Xavier Montalban, MD, PhD, Chair and Director of the Department of Neurology and Neuroimmunology at Vall d’Hebron University Hospital in Barcelona, and colleagues agreed to investigate 10 questions related to treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns, and treatment of MS in pregnancy. They developed the guideline following the recommendations of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group, along with EAN recommendations for writing a neurologic management guideline. Literature searches relied upon databases such as the Cochrane Central Register of Controlled Trials, Excerpta Medica, and Medical Literature Analysis and Retrieval System Online.

Xavier Montalban, MD, PhD

The authors evaluated data for all disease-modifying treatments (DMTs) approved by the European Medicines Agency at the time of publication. They did not consider combination therapies, complementary or alternative medicine, or symptomatic treatment. Although focused on Europe, the guideline does not account for regulatory or organizational issues specific to any European country.

Strong Recommendations

Dr. Montalban and colleagues agreed upon 21 recommendations and consensus statements. The recommendations were categorized as strong or weak, according to the quality of evidence and the risk–benefit balance. The authors formulated consensus statements on questions for which evidence was insufficient to support a formal recommendation.

The first of the guideline’s three strong recommendations is that neurologists offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) and an abnormal MRI with lesions suggestive of MS who do not fulfill criteria for MS. The second is to offer early treatment with DMTs to patients with active relapsing-remitting MS, as defined by clinical relapses or MRI activity. The authors defined active lesions as contrast-enhancing lesions or new or unequivocally enlarging T2 lesions assessed at least annually. This recommendation also applies to patients with CIS who fulfill current diagnostic criteria for MS. The third strong recommendation is to offer a more efficacious drug to patients treated with interferon or glatiramer acetate who show evidence of disease activity.

Weak Recommendations

Nine of the guideline’s recommendations are categorized as weak. For example, neurologists should consider treating patients with active secondary progressive MS with interferon beta-1a or -1b, taking into account the treatments’ “dubious efficacy,” as well as their safety and tolerability, according to the authors. Neurologists should consider mitoxantrone, ocrelizumab, and cladribine for this population. The authors recommend considering ocrelizumab as a treatment for patients with primary progressive MS.

As a way of monitoring treatment response, the authors recommend that neurologists consider combining MRI with clinical measures when evaluating disease evolution in treated patients. When making treatment decisions in the event of safety concerns, neurologists should consider the possibility that disease activity may resume or rebound if treatment is stopped, particularly with natalizumab, said Dr. Montalban and colleagues. Continuation of DMT treatment should be considered for patients who are clinically stable, who have stable MRI, and who have no problems with safety or tolerability, according to the guideline.

“For women planning a pregnancy, if there is a high risk of disease reactivation, consider using interferon or glatiramer acetate until pregnancy is confirmed,” said the authors. “In some very specific (active) cases, continuing this treatment during pregnancy could also be considered.” Delaying pregnancy is advisable for women with persistent high disease activity. If such a woman decides to become pregnant or has an unplanned pregnancy, neurologists may consider treatment with natalizumab throughout pregnancy after a full discussion with the patient of the potential implications. “Treatment with alemtuzumab could be an alternative therapeutic option for planned pregnancy in very active cases, provided that a four-month interval is strictly observed from the latest infusion until conception,” said Dr. Montalban and colleagues.

Consensus Statements

Several of the guideline’s consensus statements relate to the monitoring of treatment response. For patients treated with DMTs, the authors recommend performing a standardized reference brain MRI within six months of treatment onset, and comparing it with a subsequent brain MRI performed 12 months after starting treatment. The measurement of new or unequivocally enlarging T2 lesions is the preferred MRI method of gauging treatment response, supplemented by gadolinium-enhancing lesions. To monitor treatment safety, the authors recommend performing a standardized reference brain MRI every year in patients at low risk for progressive multifocal leukoencephalopathy (PML), and every three to six months in patients at high risk for PML.

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