Several encouraging advances have been made in the treatment of relapsing-remitting multiple sclerosis (MS) in recent years. Thus, the first orally administered substance – fingolimod – now also has a firm place in their basic therapy.
In relapsing-remitting MS, the goal of therapy is to resolve relapsing symptoms as quickly and as completely as possible, as each relapse can leave residual symptoms. In addition to relapse therapy, which is usually provided by steroids and plasmapheresis at most, initiation of basic therapy is important to reduce relapse frequency and severity and to slow overall disease progression. “Today we know that basic therapy should be started as early as possible, which is why today we initiate therapy as soon as the diagnosis of MS is confirmed or if later manifest MS is likely in a CIS (“clinically isolated syndrome”),” emphasized PD Dr. med. Michael Linnebank, University Hospital Zurich. Early therapy, by preventing the disease from becoming fully active, appears to set the stage for a more favorable long-term course [1].
Baseline therapeutic agents may be either beta-interferons or glatiramer acetate injected subcutaneously or intramuscularly, or oral fingolimod. If the basic therapy does not lead to a sufficient reduction of disease activity, the therapy can be escalated, e.g. from an injection preparation to the oral fingolimod or to natalizumab (Fig. 1). Mitoxantrone is rarely used today because of the risks (cardiac, tumor development).
Oral basic therapy of MS with fingolimod
In Switzerland, fingolimod (Gilenya®) is approved as a basic therapy for relapsing-remitting MS to reduce relapse frequency and delay disability progression. Fingolimod is very similar to sphingosine, docks with sphingosine-1-phosphate (S1P) receptors, and interferes with the sphingolipid metabolism of lymphocytes, preventing them from exiting the lymph nodes. “Fingolimod therapy reversibly redistributes the lymphocytes. They are iin the lymphatic tissue and no longer in the blood and consequently can no longer pass from the blood into the nervous system and cause inflammation there,” says the expert.
The two key studies on fingolimod are the TRANSFORMS [2] and FREEDOMS [3] studies, which showed that fingolimod was superior to placebo and interferon-β-1a in several parameters: reduction in annual relapse rate, lower increase in disability, reduction in inflammatory activity on MRI, and reduction in brain volume decline.
The tolerability of fingolimod is generally good, but some points must be taken into account: For example, macular edema may occur as a rare complication. An ophthalmological check-up should therefore be performed before the start of therapy and after three to four months of treatment. Similarly, laboratory tests should be performed regularly before and during treatment, and dermatologic examinations should be performed in patients at increased risk for skin malignancies. In women of childbearing age treated with fingolimod, care must be taken to ensure effective contraception, as the substance is teratogenic.
Source: Lunchsymposium, Medidays 2013, September 2-6, 2013, UniversitySpital Zurich
Literature:
- Tintoré M: Early MS treatment. Int MS J 2007; 14: 5-10.
- Cohen JA, et al: Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362: 402-415.
- Kappos L, et al: A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010; 362: 387-401.
