Multiple sclerosis (MS) is probably the neurological disease which has seen the most powerful development of new treatments in the last 15 years, and the next 5 years also promise to deliver more options. Furthermore, MS also responds to disease modifying agents, both due to the type of drugs and a better use of old drugs. A key concept which gained global acceptance is the importance of starting treatment as early as possible because irreversible tissue damage occurs very early in the central nervous system, even if frequently masked by the redundancy and the plasticity of the nervous system. Imaging and electrophysiological studies documented that patients may frequently have extended involvement of nervous pathways without corresponding signs and symptoms. Even if the pathophysiological basis of the progressive phase of the disease is not completely elucidated, the disease burden seen with magnetic resonance imaging (MRI) and evoked potentials predict those patients at higher risk of reaching the milestones of the disease evolution earlier on the continuum.
Interferons (IFNs) and glatiramer acetate have been used for more than 15 years, confirming the excellent safety profile already found in pivotal clinical trials. Old immunosuppressive treatments, if used at appropriate doses, have a strong anti-inflammatory effect, similar in magnitude to some more recent treatments, such as fingolimod and cladribine. Unfortunately at these doses and with prolonged treatment, serious adverse effects can be seen in a significant proportion of patients. New treatments have been developed to provide a better efficacy/safety profile, which has been confirmed by short term phase III clinical studies, however only clinical use in a large number of patients over a prolonged observation period can provide definitive answers.
From a general point of view, treatments with a strong efficacy tend to have a greater risk of adverse effects; nevertheless the different mechanisms of action of disease modifying treatments also imply a specific type of risk, such as progressive multifocal leukoencephalopathy (PML) with natlizumab, idiopathic thrombocytopenic purpura after treatment with alemtuzamb, herpes zoster reactivation after cladribine and herpes virus infections after fingolimod. Risks may also vary from patient to patient, for example the risk of PML in natalizumab treated patients is very low in patients seropostive for the virus and high in seropositive patients who were previously treated with immunosuppressive drugs.
Individualizing treatment is the second key point of MS therapy. Future developments in pharmacogenomics and the availability of new body fluid biomarkers in combination with the powerful prognostic information provided by MRI and neurophysiology may help to orient the physician in the choice of an appropriate treatment for each patient at a given time point.
The third key point to consider in MS therapy is the treatment regimen. The concept of first, second and third line treatment based on the specific safety/efficacy profile of the drug is fundamental for escalating therapy. However the rationale of early treatment suggests a more aggressive approach, at least in patients with negative prognostic factors, the so called induction strategy.
This monograph which addresses present and future MS therapies, with contributions from some of the major experts in the field, presents detailed profiles of each intervention and suggests how to optimize the use of each drug. This issue of the series Hot Topics in Neurology and Psychiatry is recommended to all health care professionals involved in the management of MS patients.