PARIS — The first real guidelines on the use of disease-modifying therapies in multiple sclerosis (MS) have been released by a European joint venture between the European Committee for Research and Treatment of Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN).
A summary of the guidelines was presented today by Xavier Montalban, MD, director of the Multiple Sclerosis Centre of Catalonia, Spain, at the 7th Joint ECTRIMS-Americas Committee for Research and Treatment of Multiple Sclerosis (ACTRIMS) 2017 meeting.
The American Academy of Neurology is also formulating guidelines on use of disease-modifying drug therapy in MS. Its guidelines were scheduled to be presented at the ECTRIMS/ACTRIMS meeting, but this did not happen.
In his scheduled presentation, Alexander Rae-Grant, MD, Cleveland Clinic Foundation, Ohio, said, “I would have loved to have presented the guidelines today…but unfortunately the data is still embargoed.” He said he was not able to comment on the timeline, the panel, or when it will be published.
Instead, Dr Rae-Grant delivered a talk about the process of guideline development. Afterwards, when pressed during the discussion on the status of the guidelines he said they were “close.”
In his presentation on the European guidelines, Dr Montalban reported that the objective of the committee was to develop a clinical practice guideline on the pharmacologic treatment of patients with MS to guide healthcare professionals in the decision-making process.
The guidelines cover the treatment of adults with MS or clinically isolated syndrome (CIS), the monitoring of treatment response, the stopping and switching of treatment strategies, and treatment in special situations, such as pregnancy.
Dr Montalban explained that the guidelines committee used the GRADE method to formulate the recommendations, which consists of evaluating the quality of the evidence and the tradeoff between benefits and harms in a two-phase consensus process. Through this process, the committee developed a recommendation for or against treatment and then assigned a strength to that recommendation (strong or weak based on the evidence, or consensus statement). Strong recommendations should be acted on and weak recommendations should be considered, he said.
Dr Montalban reported 20 main recommendations in the guidelines. “Some of them are very obvious, but we wanted to set out the evidence base,” he said.
The guidelines are as follows:
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The entire spectrum of disease-modifying drugs should be prescribed only in centers with adequate infrastructure to provide proper monitoring of patients, comprehensive assessment, detection of side effects, and capacity to address them properly. (Consensus statement)
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Offer interferon or glatiramer acetate to patients with CIS and abnormal MRI findings with lesions suggesting MS who do not fulfill full criteria for MS. (Strong)
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Offer early treatment with disease-modifying drugs in patients with active relapsing-remitting MS (RRMS), as defined by clinical relapses and/or MRI activity (active lesions: contrast-enhancing lesions; new or unequivocally enlarging T2 lesions assessed at least annually). (Strong).
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For active RRMS, choosing among the wide range of available drugs from the modestly effective to the highly effective will depend on patient characteristics and comorbidity, disease severity, drug safety profile, and accessibility of the drug. (Consensus statement)
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Consider treatment with interferon in patients with active secondary progressive MS (SPMS), taking into account, in discussion with the patient, the dubious efficacy, as well as safety and tolerability profile. (Weak)
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Consider treatment with mitoxantrone in patients with active SPMS, taking into account the efficacy and specifically the safety and tolerability profile of this agent. (Weak)
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Consider ocrelizumab for patients with primary progressive MS. (Pending European approval).
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Always consult the summary of product characteristics for dosage, special warnings, and precautions of use, contraindications, and monitoring of side effects and potential harms. (Consensus statement).
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Consider combining MRI with clinical measures when evaluating disease evolution in treated patients. (Weak)
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When monitoring treatment response in patients treated with disease-modifying drugs, perform standardized reference brain MRI within 6 months of treatment onset and compare the results with those of further brain MRI, typically performed 12 months after starting treatment. Adjust the timing of both MRIs, taking into account the drug’s mechanism and speed of action and disease activity, including clinical and MRI measures. (Consensus statement).
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When monitoring treatment response in patients treated with disease-modifying drugs, the measurement of new or unequivocally enlarging T2 lesions is the preferred MRI method, supplemented by gadolinium-enhancing lesions for monitoring treatment response. Evaluation of these parameters requires high-quality standardized MRI scans and interpretation by highly qualified readers with experience in MS. (Consensus statement).
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When monitoring treatment safety in patients treated with disease-modifying drugs, perform standard reference MRI every year in patients at low risk for progressive multifocal leukoencephalopathy (PML), and more frequently (3 to 6 months) in patients at high risk for PML (JC virus positivity, natalizumab treatment duration over 18 months) and in patients at high risk for PML who switch drugs at the time the current treatment is discontinued and the new treatment is started. (Consensus statement).
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Offer a more efficacious drug to patients treated with interferon or glatiramer acetate who show evidence of disease activity, assessed as recommended above. (Strong)
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When deciding on which drug to switch to, in consultation with the patient, consider patient characteristics and comorbidities, drug safety profile, and disease severity/activity. (Consensus statement)
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When treatment with a highly efficacious drug is stopped, whether due to inefficacy or safety, consider starting another highly efficacious drug. When starting the new drug, take into account disease activity (clinical and MRI; the greater the disease activity, the greater the urgency to start new treatment), the half-life and biological activity of the previous drug, and the potential for resumed disease activity or even rebound (particularly with natalizumab). (Consensus statement)
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In treatment decisions, consider the possibility of resumed disease activity or even rebound when stopping treatment, particularly with natalizumab. (Weak).
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Consider continuing a disease-modifying drug if the patient is stable (clinically and on MRI) and shows no safety or tolerability issues.
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Advise all women of childbearing potential that disease-modifying drugs are not licensed during pregnancy, except glatiramer acetate. (Consensus statement)
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For women planning a pregnancy, if there is a high risk for disease reactivation, consider using interferon or glatiramer acetate until pregnancy is confirmed. In some very specific (active) cases, continuing this treatment during pregnancy could also be considered. (Weak)
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For women with persistent high disease activity, it would generally be advised to delay pregnancy. For those who still decide to become pregnant or have an unplanned pregnancy, treatment with natalizumab throughout pregnancy may be considered after full discussion of potential implications; or treatment with alemtuzumab could be an alternative for planned pregnancy in very active cases provided that a 4-month interval is strictly observed from the latest infusion until conception. (Weak)
The final version of the guidelines will be published presently in both the Multiple Sclerosis Journal and the European Journal of Neurology.
Experts polled by Medscape Medical News about the guidelines were quietly supportive.
Jeffrey Cohen, MD, Cleveland Clinic, commented: “Overall they are reasonable. Because of the goal of them being evidence based and the complexity of the process, they are rather conservative.”
Edward Fox, MD, Multiple Sclerosis Clinic of Central Texas, Round Rock, said, “The guidelines are important. The conclusions are not very strong but they are at least ones we can use as general guidelines to support what we are already doing in clinical practice.”
“We have a new landscape in treating the disease so we need a new set of consensus statements about the treatment of MS,” Dr Fox elaborated. “The last time we had any sort of consensus statement on treatment we had far fewer drugs and they were much more similar to one another. Now we have a different tier of drugs and different concerns about safety and efficacy, so we need an updated overview. This is merely an exercise to ensure practising neurologists are following current practice standards.”
He added: “I strongly suspect the American guidelines will be similar, but I worry that they may not be so specific regarding change of medications.”
Tomas Kalincik, MD, Royal Melbourne Hospital, Australia, called the guidelines “an important start.”
“Every patient is not the same, and treatment doesn’t follow a one-size-fits-all approach, but it is good to have a general recommendation that we can fall back on,” he said. “But we have to recognize the individuality of each patient and each clinical scenario.”
7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017 meeting. Abstracts 229 and 230. Presented October 27, 2017.
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