Therapies for multiple sclerosis in the USA include over 20 different drugs. Siponimod – Mayzent –  and Cladribine – Mavenclad – have become FDA-approved this year. Cladribine is a more effective theray, with significant safety problems, including the development of malignancies. Thus it is reserved for people that have failed other therapies.

Almost 1 million people have MS in the USA, and perhaps half, or one third, may have it in Brasil. There are numerous position papers about which patients should receive which drugs, and in some countries, like Brasil, the choice is already decided by the public health system that buys the drugs and provides them upon recommendation of neurologists.

Alex Era-Grant, of the Cleveland Clinic, cooperated with the guidelines of the American Academy of Neurology. He thinks each physician needs to become acquainted with a few drugs. With time they will develop their own experience and choose more wisely. That is what doctors, and other professionals, do.  Older drugs, like the interferons and glatiramer acetate, offer a similar effect, of approximately 30% reduction in disease activity without na effect of progression of the neurological déficit.

Some compounds were withdrawn from the Market because of safety concerns, as daclizumab, because of meningitis and encephalitis. Newer oral drugs, like fingolimod, dimethyl-fumarate and teriflunomide, decrease relapses by 35-60%, and have their own therapeutic profile. The greater problem has been with progressive multifocal encephalitis and fingolimod and dimethyl-fumarate. PML may be difficult for clinicians to diagnose, as patients may confound the progressive neurological déficit, cluminess, weakness, visual, memory or mental signs, with those of MS. Low lymphocye counts, bradycardia, fungal infections, acute liver damage and tuberculosis are the possible complications of these drugs. Siponimod is quite similar to fingolimod, with the same therapeutic and safety profile.

The injetcibles, natalizumab and alemtuzumab, are the most effective therapies for multiple sclerosis available, reducing disease activity by 50-80%. The same goes for ocrelizumab and rituximab. But along with mitoxantrone, they have the worst safely profile, with malignancies, infection, boné marrow and cardiac toxicity. Alemtuzumab is linked to significant auto-immunity, patients develope de novo autoimune diseases, like nephritis and thyroiditis, because of the treatment.

New evidence suggests that patients benefit from therapies for multiple sclerosis given early, especially before 50 years of age. This may be linked to the development of progressive MS, and neurodegenerations is already a fact, rather than mostly inflammmation, as in younger patients. These are the ones that should risk more and have the more eficiente therapies for multiple sclerosis.

Wallin et al. Neurology 2019, 92: e1029-e1040

O’Connor et al. Lancet Neurol 2009, 8;889-897

Weideman et al. Front Neurol 2017, 8:577

All cited in Gina Shaw. Neurology Today May 23, 2019

These statements, strangely, ignore cyclophosphamide and the stem cell therapies for multiple sclerosis that are associated with cyclophosphamide, which may be appreciated in other articles on this site.

Dr Paulo de Bittencourt

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