European MS Guidance Taking Shape

LONDON -- European researchers are putting finishing touches on the first-ever clinical guideline for drug treatment of multiple sclerosis, with a preview presented here in advance of its final release.

The guideline will discuss the considerations involved with each of the dozen available drugs but with little specific advice on how to choose among them, said Susana Otero-Romero, MD, of the Multiple Sclerosis Center of Catalonia in Barcelona, speaking at the European Committee for Treatment and Research in Multiple Sclerosis meeting here.

Selecting a drug will depend on patient characteristics, disease severity, drug safety profile, and accessibility – in combination with a conversation with the patient about their preferences, she said.

"The evidence thus far does not allow us to prioritize drugs," Otero-Romero told MedPage Today. "We're lacking head-to-head comparisons."

The guideline will also endorse ocrelizumab (tentative brand name Ocrevus) for primary progressive MS if the drug is approved before publication, Otero-Romero said.

Many expect the drug to be approved in the U.S. before the end of the year, and Otero-Romero said the guideline will likely be published by the beginning of next year.

"The guideline will come out whenever it's ready, but if in the meantime we have approval of ocrelizumab, we will recommend it," she said. "It has been tested in PPMS and is the first to show some effect."

The guideline was developed jointly by ECTRIMS and the European Academy of Neurology, via a committee chaired by Xavier Montalban, MD, of Vall d'Hebron Hospital in Barcelona, and Ralf Gold, MD, of Ruhr University Bochem in Germany, and coordinated by Otero-Romero, and follows the GRADE methodology for assessing evidence.

During a platform presentation here at a late-breaker session, Otero-Romero offered "a taste" of what the full-length guideline will say about MS drug therapies when it is finalized and published.

It will generally recommend that the "entire spectrum of disease-modifying drugs should only be prescribed in centers where there is adequate infrastructure" to provide proper monitoring, comprehensive assessment, and detection of side effects and ability to promptly address them, Otero-Romero said.

That does not mean that treatment should only take place in highly specialized centers, Montalban explained, in response to an audience member's objection that the guideline appeared to exclude community-based neurology clinics.

"If you can follow the patient and be aware of side effects and manage them, that's perfectly okay," he said. "It does not have to be done at specific MS centers."

Otero-Romero noted that treatment is "getting especially complicated, and you need to make sure you have all the tools to properly monitor patients and address side effects."

"For instance, you need to make sure you're really complying with all the safety monitoring required for a drug like natalizumab (Tysabri), which is one of the most complex ones," she said. "Do you have access to MRI? Do you have MS nurses? ... If the patient says, 'I want to become pregnant,' can you handle that? And if you can't take care of that, can you refer the patient when necessary?"

For clinically isolated syndrome (CIS) patients who have an abnormal MRI but don't fulfill MS criteria, the guidance recommends consideration of interferon or glatiramer acetate (Copaxone). Otero-Romero noted that these are the only agents for which there is specific, published evidence of effectiveness in CIS.

In relapsing-remitting MS (RRMS), physicians should offer treatment early to those with relapses and/or MRI activity, Otero-Romero said.

Choosing between a the range of "modestly to highly effective" drugs will depend on several factors, including patient characteristics and comorbidities, disease activity/severity, drug safety profile, and it accessibility, in conjunction with a dialogue with the patient as to his or her preferences.

For monitoring, doctors should consider using MRI combined with clinical measures to assess disease evolution in patients on disease-modifying drugs.

When monitoring patient response to DMDs, consider performing a standard reference brain MRI within six months of the start of therapy, and compare that with further brain MRI, typically performed 12 months later.

In the case of a poor response to therapy interferon or glatiramer acetate, physicians should offer a more efficacious drug, and if a highly efficacious drug is stopped for inefficacy or safety, consider another highly efficacious drug, the guidance states.

When switching between highly efficacious drugs, take into account disease activity, half-life and biological activity of the previous drug, and the potential for disease activity to resume or rebound, particularly with natalizumab, Otero-Romero said.

Among other potential treatments not mentioned in the guideline at this point: vitamin D screening and supplementation, and stem cell therapy.

There are currently no other comprehensive guidelines for MS treatment, Otero-Romero said. There has only been some consensus on specific topics like treatment of attacks, and the use of particular treatments like mitoxantrone and natalizumab.

The American Academy of Neurology is taking comments on a draft version of its evidence-based guidelines for MS disease-modifying therapies through Oct. 8.

Otero-Romero said the guidelines may also be helpful in terms of making certain treatments available for more patients. In the U.K., for instance, regulators have declined to pay for off-label rituximab for MS patients.

"If these guidelines could be used to change some local regulations, that would be fine," she said.

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