Epub: Izquierdo et al. Five-year results from a phase 2 study of oral fingolimod in relapsing multiple sclerosis. Mult Scler. 2013 Nov 30.
Fingolimod remains effective over 5 years with no new safety signals. #ClinicSpeak #MSBlog #MSResearch
“It is always reassuring to see long-term extension data published from clinical trials. The study below shows that in MSers who have received fingolimod for 5, or more years, the drug remains effective with MSers have a low relapse rate and low MRI activity and no new safety signals have emerged.”
“This data mirrors the clinical experience of using fingolimod in the real-world. The main issue with fingolimod are the initial effects of the drug on the heart, or the so called first dose effect, which is the transient slowing of the heart rate when the drug is first started. This means that all MSers have to have a cardiac screen with an ECG, or EKG, to make sure there are no abnormalities of cardiac rhythm. In addition, MSers who are on cardiac drugs that may slow the heart and interact with fingolimod may not be able to start fingolimod. Providing your heart is normal you need to spend 6 hours in hospital for the first-dose observation. Rarely, in less than 0.5% of MSers, fingolimod may cause a transient block in the conduction of electricity in the heart, i.e. a heart block, which may need to be treated with a temporary pacemaker. The heart block, however, typically resolves spontaneously.If the heart rate remains low after 6 hours the observation period may need to be extended and very rarely the MSer may needed to be admitted for overnight observation. In our experience the heart monitoring is not cumbersome and MSers tolerate it well.”
“As fingolimod is an a drug that suppresses your immune system you need to be vigilant about infections. As it is an immunosuppressant you are not allowed to have live vaccines whilst on the drug. This is why we test you to see if you have been infected in the past with the chickenpox virus, or varicella-zoster virus. If you don’t have antibodies against the chickenpox virus we assume you have not been infected with the virus and we vaccinate you before starting fingolimod. In some parts of the world where TB, or tuberculosis, is common we may screen you for latent TB. If positive for latent TB we have to give you a short course of anti-TB drugs. In all the MSers I have started on fingolimod I have only needed to do this once. Please note as you are unable to have live vaccines on fingolimod you need to consider travelling to areas with exotic viruses, for example yellow fever, with care. The current yellow fever vaccine is a live vaccine and hence you can’t be immunized against the virus before you travel. If you do decide to go to a yellow fever area, and you are on fingolimod, you need to take precautions and try and prevent yourself being bitten by mosquitoes; mosquitoes transmit yellow fever.”
“What about ongoing monitoring? Once you on fingolimod we need to check your eyes, or retina, at about 3-4 months after starting to make sure you don’t develop swelling of the retina or so called macular oedema. If this should occur, fingolimod needs to be stopped and the oedema clears spontaneously. You also have to have your liver function tests and blood counts monitored regularly. A small number of MSers develop abnormal liver tests and fingolimod may have to be stopped, and restarted. All MSers who start fingolimod develop a low lymphocyte count; this is how the drug works. Fingolimod traps the lymphocytes in lymph nodes; it does not kill them hence they are still in the body, but not in the blood. If fingolimod is stopped the lymphocyte counts return to normal within a period of 6 to 8 weeks. If the lymphocyte count drops below 200 per mL we are meant to stop the drug. However, as there are no adverse events reported in MSers with lymphocyte counts below 200 I tend to continue the drug. I may switch to alternate day dosing, i.e. every second day, if the MSer concerned becomes anxious or the counts go lower than 100. If you stop the drug for longer that 2 weeks you need to repeat the first dose monitoring.”
“Overall our experience with fingolimod has been positive. MSers who start the drug are doing well. As it is one of the highly-effective drugs they should continue to do well. What I find quite amazing is that the NICE cost-effectiveness model that are used to assess whether or not DMTs are cost-effective and can be used in the NHS, the models assume that there is a waning of the therapeutic effect. I am not sure why? The data set below suggests the drug continues to work without a waning effect; well at least for 5 years. I can only speculate that the assumption that the therapeutic effects of the drug wanes over time helped the NHS get a further discount on the price. I am not sure if you are aware that the NHS does not pay the list price for fingolimod, but a discounted price. The discounted price is a secret; if it gets out it will allow other nations to drive a hard bargain and also demand a bigger discount.”
“One of the interesting aspects of the biology of fingolimod is the fact that it not only works on the immune system, but may have positive effects on cells within the central nervous system. There are suggestions that it may promote remyelination and it may be neuroprotective. Fingolimod is one of the drugs that has a positive impact on brain atrophy or brain shrinkage; this effect is seen within the first 6 months and is significant across at least the first 2 years of treatment.”
“If any of you are on fingolimod it would be nice for other readers to hear about your experience. Thank you.”
Background: The investigators present here results at 60 months, from the extension component of a phase 2, randomized, placebo-controlled, double-blind, six-month study evaluating oral fingolimod (1.25 mg or 5 mg daily) in relapsing MS.
Methods: Placebo treated MSers from the core study were re-randomized to fingolimod 1.25 mg or 5 mg in the extension. All MSers received 1.25 mg fingolimod after the month 24 visit. A total of 140/281 (49.8%) patients completed month 60.
Results: Fingolimod treatment was associated with a low annualized relapse rate (0.2 relapses/ year), low MRI activity, and a modest rate of disability progression in those treated for five years. No new safety issues were reported.
Conclusions: Fingolimod has a durable effect, both clinically and on MRI, and no new safety signals have emerged after 5 years of treatment.