Who is a candidate for Gilenya?
MS experts from central and eastern Europe have published recommendations on where Gilenya (fingolimod) fits in the overall treatment plan for people with MS (Fazekas and colleagues. Front Neurol 2013;4:10. The free full text can be found in the MSology Library under Treatment Guidelines).
Gilenya is the first oral medication to become widely available to treat MS. Drug approval was based on the results of two phase III studies. In the FREEDOMS trial, Gilenya significantly reduced the relapse rate by 54% and the risk of 6-month disability progression by 37% compared to a placebo (Kappos and colleagues. N Engl J Med 2010;362:387-401; free full text at www.nejm.org/doi/pdf/10.1056/NEJMoa0909494). In the TRANSFORMS study, Gilenya was shown to be significantly more effective than Avonex; the relapse rate was 52% lower with Gilenya compared to the interferon (Cohen and colleagues. N Engl J Med 2010;363:402-415; free full text at www.nejm.org/doi/pdf/10.1056/NEJMoa0907839).
Some tests are needed before starting Gilenya and a 6-hour observation period is required during the first dose to monitor heart activity. The most common side effects are infections, headache, diarrhea, back pain and cough.
The new recommendations outline three scenarios where Gilenya should be used. In people with highly active disease (e.g. two or more disabling relapses in the previous year and significant disease activity on MRI), Gilenya can be the first-choice drug. The strategy is to try to get MS under control quickly rather than start with a less effective drug.
The more common scenario is to start Gilenya after an initial treatment (e.g. an interferon or Copaxone) has failed. This is the approved use of the drug in Europe and Canada (in the U.S. and some other countries the drug can be prescribed first for anyone with MS). According to the European group, treatment failure should be defined as any evidence of continuing disease activity despite being on a therapy. This could mean one or more relapses, a significant number of lesions on MRI, intolerable side effects with a drug, or even finding yourself unable to keep injecting regularly. Only 30% or so started on a first-choice injectable respond well to treatment; many have a middling response that could be better; and about 1 in 4 will not respond (Maurer and colleagues. Eur J Neurol 2011;18:1036-1045).
If treatment does fail or a person has problems with an injectable, there’s an urgency to switch to a more potent medication – either Tysabri or Gilenya – to get the disease activity under control. The choice of Tysabri or Gilenya will depend on a number of factors. Since there is a risk of developing PML (progressive multifocal leukoencephalopathy, a potentially fatal brain disease) with Tysabri, it’s important to be tested for the presence of the JC virus, which causes PML. This requires a blood test to check for antibodies for the JC virus. If a person is antibody-positive (meaning they’ve been exposed to the virus), it’s generally recommended to limit the duration of Tysabri treatment to two years since the risk of PML goes up substantially after prolonged exposure to the drug. For people who have been treated at some point with an immunosuppressant, the PML risk at 2 years is about 1 in 200 if you’re JC virus antibody-negative (Bloomgren and colleagues. N Engl J Med 2012;366:1870-1880). But the risk is much higher – about 1 in 90 – if you’re antibody-positive, so Gilenya may be the better choice for these people.
For the minority of people who aren’t JC virus antibody-positive, the choice of Tysabri or Gilenya is less clear-cut. People with significant heart disease (such as a heart rhythm disturbance) may opt not to take Gilenya because the drug has effects on the heart. Otherwise, the decision will depend a lot on personal preference. For example, Tysabri is administered once a month by injection at an infusion centre whereas Gilenya is taken daily as an oral capsule.
The third scenario where Gilenya is recommended is after a course of treatment with Tysabri. As mentioned above, it’s generally advised to stop Tysabri after two years because of the increasing risk of PML. However, quitting cold turkey isn’t a good idea because there’s a high risk of a severe MS flare-up as the drug wears off. In this case, the European recommendations advise starting with Gilenya about 2-3 months after stopping Tysabri to minimize the risk of worsening MS (Havla and colleagues. J Neurol 2013;260:1382-1387).
The European recommendations were based on an expert conference held in Vienna in 2011, so they don’t consider newer medications that are now available in some countries (i.e. Tecfidera [BG-12] and Aubagio [teriflunomide]). However, the same overall treatment approach could apply for people who start on one of these oral drugs (rather than an injectable) and experience ongoing MS activity or tolerability issues. It may be that people who don’t respond adequately to Tecfidera may be better off with Gilenya. No cases of PML have been reported with Tecfidera in people with MS, however, there are rare cases with this class of drugs (Ermis and colleagues. N Engl J Med 2013;368:1657-1659; van Oosten and colleagues. N Engl J Med 2013;368:1658-1659; Sweetser and colleagues. N Engl J Med 2013;368:1659-1661). So doctors will need to determine what the risk of PML is when switching from Tecfidera to Tysabri.
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