The goal of therapy in patients with MS is to prevent relapses and progressive worsening of the disease. The documentation of therapeutic advances in MS is dependent on large, randomised, controlled clinical trials because of the highly variable and unpredictable course of the disease and the difficulty in precisely measuring neurologic disability.

Immunosuppressive drugs that dampen certain aspects of immune system function were used initially, but they have never found widespread acceptance because the various studies have met with limited success as a result of variable efficacy and considerable toxicity (especially with long-term use), mainly because of the induction of bone marrow suppression.

More recently, large, randomised, controlled trials have been performed with substances that should be seen as immune modulators rather than as immune suppressors. These studies have led to the regulatory approval of a series of “disease modifying” agents [Avonex®, Betaseron® (Betaferon® in Europe), Copaxone®, Rebif® and Tysabri® worldwide, and mitoxantrone (Novantrone®) in North America]. Although there is some evidence for a reduction in the rate of progression of neurologic impairment and disability, none of these agents have been shown to achieve a sustained remission, complete halt of further progression, or substantially alleviate long-standing disability.

Therefore, in individual patients, decisions to initiate treatment should be based on the course of that patient’s disease. Patients (and often family members) should actively participate in every treatment decision. There is considerable inter-individual variability between patients. Faced with the same clinical scenario and the same, careful review of what is known about the value of the approved medications, some patients will decide to delay treatment, whereas others will choose to be started on treatment as soon as the diagnosis has been established. On the one hand, approximately 10–20 percent of patients have relatively benign disease, so not every patient may require disease-modifying therapy. On the other hand, there is emerging evidence that disease modifying treatments are more effective when started early in the disease course, maybe as early as the first attack, and treatment should certainly not be postponed until after persistent neurologic deficits have occurred because none of the available compounds reverse fixed deficits. Although long-term follow-up of patients who had a first attack indicates that the likelihood of a second clinical event and the development of disability increases with certain clinical characteristics (progressive course of disease, sphincter or motor symptoms at onset, male sex, or high attack frequency within the first years) as well as with the lesion load on brain MRI, determining the exact future prospectives for a given individual is still not possible because the prognostic value of these factors is only modest. Therefore, disease-modifying therapy should be now be considered early in the course for patients, in some cases, immediately after the first attack.

Before long-term therapies are implemented, it is extremely important that counselling about realistic objectives regarding efficacy and side-effects takes place, because overly optimistic expectations may complicate treatment. Patients who understand these issues are more likely to remain compliant with the medications once the decision has been reached to commence treatment.