MedicalResearch.com Interview with:
Marcia Kayath, MD
Vice President and Head
US Clinical Development and Medical Affairs US General Medicines
Novartis Pharmaceuticals Corporation
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Injectable disease-modifying therapies (DMTs) are typically used first-line in patients with multiple sclerosis (MS), but discontinuation of injectable DMTs is common, especially within the first 12 months of treatment1,2. PREFERMS is the largest, prospective, randomized, active-controlled, open-label study to evaluate patient retention in patients with relapsing-remitting multiple sclerosis (RRMS).
In the 12-month, Phase IV study, a total of 875 patients were randomized (1:1) to Gilenya® (fingolimod) 0.5 mg or to a pre-selected injectable DMT (IFNβ-1a, IFNβ-1b or glatiramer acetate), and followed up quarterly for 12 months3. After a minimum of 3 months of treatment, a single on-study treatment switch was allowed, however, switches due to efficacy or safety were allowed (based on patient-doctor consultation) at any month following randomization3. The primary endpoint was to compare the patient retention on randomized treatment over 12 months3. This study was powered for the primary endpoint (retention rate)3. The study was not powered to detect the treatment difference in the secondary efficacy endpoints or treatment effects related to switching study medication3.
In a pre-planned analysis at the end of randomized treatment (when patients either switched or discontinued randomized treatment), significantly more patients were satisfied with treatment in the Gilenya group compared to the group receiving injectable DMTs, 77.4% vs. 47.7%, respectively (p<0.0001)3. Gilenya also reduced brain volume loss compared with injectable DMTs1. At the end of randomized treatment, the exposure-adjusted mean percentage of brain volume loss in the Gilenya compared to the injectable DMT group was 0.48% vs. 0.75%, respectively (p<0.001)3.
At the end of randomized treatment, the between-group differences in patient satisfaction and brain volume loss favored Gilenya over injectable DMTs3. By the end of the study, a high number of patients switched from injectable DMTs to Gilenya (90.5%, n=257) and the between-group differences became similar3. This is potentially due to the high number of patients who switched from the injectable DMT group to Gilenya3.
Among the patients who changed therapy from injectable DMTs to Gilenya, the rates of overall adverse events (AEs)/per patient-year decreased from 10.854 at end of randomization to 6.438 at end of study; rates for AEs/per patient-year leading to discontinuation (1.652 vs. 0.657) and rates of serious AEs/per patient year remained similar (0.06)3. Overall, the Gilenya safety profile was consistent with data from previous studies.
MedicalResearch.com: What should readers take away from your report?
Response: Injectable DMTs can make it hard for patients to stay on therapy, and lack of adherence can lead to disability progression. While we want to be mindful that PREFERMS was not specifically designed to detect treatment effects related to switching, our findings suggest an oral therapy may increase treatment satisfaction among patients with relapsing multiple sclerosis compared to injectable therapies.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: We are still evaluating how these findings may inform our future research efforts in MS.
MedicalResearch.com: Is there anything else you would like to add?
Response: Multiple Sclerosis remains a disease area with high unmet needs. Advancing research in MS is important to help improve patient outcomes and address the key challenges healthcare providers face on a day-to-day basis.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
1. Hunter SF, Cascione M, Thomas F et al. PREFERMS study: fingolimod switch effect on patient retention, key clinical outcomes Bayas A. Improving adherence to injectable disease-modifying drugs in multiple sclerosis. Expert Opin Drug Deliv. 2013;10:285-7.
2. Jongen PJ, Lemmers WA, Hupperts R et al. Persistence and adherence in multiple sclerosis patients starting glatiramer acetate treatment: assessment of relationship with care received from multiple disciplines Patient Prefer Adherence. 2016;10:909-17.
3. Hunter SF, Cascione M, Thomas F et al. PREFERMS study: fingolimod switch effect on patient retention, key clinical outcomes and patient satisfaction. Abstract: EP1496. ePoster presented at the 2016 Annual European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, London, UK, September 14-17, 2016.
Below are the indication for Gilenya and important safety information. Please also see Gilenya Prescribing Information.
Gilenya is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS) in adults. Gilenya can decrease the number of MS flare-ups (relapses). Gilenya does not cure MS, but it can help slow down the physical problems that MS causes.
Important Safety Information:
You should not take Gilenya if in the last 6 months you experienced heart attack, unstable angina, stroke or warning stroke, or certain types of heart failure. Do not take Gilenya if you have an irregular or abnormal heartbeat (arrhythmia), including a heart finding called prolonged QT as seen on an ECG, or if you take medicines that change your heart rhythm. Do not take Gilenya if you are allergic to fingolimod or any of the other ingredients.
Gilenya may cause side effects such as:
• Slow heart rate, especially after first dose. You will be monitored by a health care professional for at least 6 hours after your first dose. Your pulse and blood pressure will be checked hourly. You’ll get an ECG before and 6 hours after your first dose. If any heart problems arise or your heart rate is still low, you’ll continue to be monitored. If you have any serious side effects, especially those that require treatment with other medicines, or if you have certain types of heart problems, or if you’re taking medicines that can affect your heart, you’ll be watched overnight. If you experience slow heart rate, it will usually return to normal within 1 month. Call your doctor, or seek immediate medical attention if you have any symptoms of slow heart rate, such as feeling dizzy or tired or feeling like your heart is beating slowly or skipping beats. Symptoms can happen up to 24 hours after the first dose. Do not stop taking Gilenya without consulting with your doctor. Call your doctor if you miss 1 or more doses of Gilenya—you may need to repeat the 6-hour monitoring.
• Increased risk of serious infections. Gilenya lowers the number of white blood cells (lymphocytes) in your blood. This will usually go back to normal within 2 months of stopping Gilenya. Your doctor may do a blood test before you start Gilenya. Gilenya may decrease the way vaccines work in your body, especially the chicken pox vaccine. Increased risk of infection was seen with doses higher than the approved dose (0.5 mg). Two patients died who took higher-dose Gilenya (1.25 mg) combined with high-dose steroids. Call your doctor right away if you have fever, tiredness, body aches, chills, nausea, vomiting, or headache accompanied by fever, neck stiffness, sensitivity to light, nausea, and/or confusion. These may be symptoms of meningitis.
• Progressive multifocal leukoencephalopathy (PML). PML is a rare brain infection that usually leads to death or severe disability. If PML happens, it usually happens in people with weakened immune systems. It is important that you call your doctor right away if you have any new or worsening medical problems that have lasted several days, including problems with thinking, eyesight, strength, balance, weakness on 1 side of your body, or using your arms and legs.
• Macular edema, a vision problem that can cause some of the same vision symptoms as an MS attack (optic neuritis), or no symptoms. If it happens, macular edema usually starts in the first 3 to 4 months after starting Gilenya. Your doctor should test your vision before you start Gilenya; 3 to 4 months after you start Gilenya; and any time you notice vision changes. Vision problems may continue after macular edema has gone away. Your risk of macular edema may be higher if you have diabetes or have had an inflammation of your eye (uveitis). Call your doctor right away if you have blurriness, shadows, or a blind spot in the center of your vision; sensitivity to light; or unusually colored vision.
• Swelling and narrowing of the blood vessels in your brain. A condition called PRES (Posterior reversible encephalopathy syndrome) has occurred rarely in patients taking Gilenya. Symptoms of PRES usually get better when you stop taking Gilenya. However, if left untreated, it may lead to a stroke. Call your doctor right away if you experience any symptoms, such as sudden headache, confusion, seizures, loss of vision, or weakness.
• Breathing problems. Some patients have shortness of breath. Call your doctor right away if you have trouble breathing.
• Liver problems. Your doctor should do blood tests to check your liver before you start Gilenya. Call your doctor right away if you have nausea, vomiting, stomach pain, loss of appetite, tiredness, dark urine, or if your skin or the whites of your eyes turn yellow.
• Increases in blood pressure (BP). BP should be monitored during treatment.
• A type of skin cancer called basal cell carcinoma (BCC). Talk to your doctor if you notice any skin nodules (shiny, pearly nodules), patches or open sores that do not heal within weeks. These may be signs of BCC.
Gilenya may harm your unborn baby. Talk to your doctor if you are pregnant or planning to become pregnant. Women who can become pregnant should use effective birth control while on Gilenya, and for at least 2 months after stopping. If you become pregnant while taking Gilenya, or within 2 months after stopping, tell your doctor right away. Women who take Gilenya should not breastfeed, as it is not known if Gilenya passes into breast milk. A pregnancy registry is available for women who become pregnant during Gilenya treatment. For more information, contact the Gilenya Pregnancy Registry by calling Quintiles at 1-877-598-7237, by e-mailing email@example.com, or by going to www.gilenyapregnancyregistry.com.
Tell your doctor about all your medical conditions, including if you had or now have an irregular or abnormal heartbeat; heart problems; a history of repeated fainting; a fever or infection, or if you are unable to fight infections due to a disease or are taking medicines that lower your immune system, including corticosteroids, or have taken them in the past; eye problems; diabetes; breathing or liver problems; or uncontrolled high blood pressure. Also tell your doctor if you have had chicken pox or have received the chicken pox vaccine. Your doctor may test for the chicken pox virus, and you may need to get the full course of the chicken pox vaccine and wait 1 month before starting Gilenya.
If you take too much Gilenya, call your doctor or go to the nearest hospital emergency room right away.
Tell your doctor about all the medicines you take or have recently taken, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tell your doctor if you have been vaccinated within 1 month before you start taking Gilenya. You should not get certain vaccines, called live attenuated vaccines, while taking Gilenya and for at least 2 months after stopping Gilenya treatment.
The most common side effects with Gilenya were headache, abnormal liver tests, diarrhea, cough, flu, sinusitis, back pain, abdominal pain, and pain in arms or legs.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit
www.fda.gov/medwatch or call 1-800-FDA-1088.
ECTRIMS presentation of the study to:
Evaluate patient retention of Fingolimod 0.5 mg vs. approved first-line injectable disease-modifying therapies (interferon ß or glatiramer acetate), over a period of 12 months in adults with Relapsing-remitting Multiple Sclerosis (PREFERMS)
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.
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