Multiple Sclerosis: What's New in MS Treatment Options?
What is Multiple Sclerosis (MS)?
Multiple sclerosis (MS) is a disease that affects the brain, spinal cord, and optic (eye) nerve, all part of the central nervous system (CNS). MS has features of a disease in which the body's immune system attacks the myelin sheaths, which are the protective covering of the nerves. When the myelin is damaged and forms scar tissue - also called sclerosis - nerve signals that travel through the CNS are disrupted and lead to the symptoms seen in MS.
The nerve damage that occurs with MS is not reversible, and MS is not curable. However, early treatment with medicine and lifestyle changes can make a positive impact on one's quality of life.
Are There Different Types of MS?
There are four different patterns for MS:
- Relapsing-Remitting MS (RRMS)
- Secondary-Progressive MS (SPMS)
- Primary-Progressive MS (PPMS)
- Progressive-Relapsing MS (PRMS)
Who Gets MS and Am I at Risk?
MS affects more than 400,000 people in the United States and about 2.5 million people worldwide. Anyone can get MS, but it occurs most frequently in white women 20 to 40 years old. MS is not a contagious disease and is not directly inherited through the genes; however, some people may have a genetic make-up that causes them to be more susceptible.
The general risk for developing MS is 1 in 750, but the risk in those with a strong family history is 1 in 40. Not everyone who gets MS develops severe symptoms; roughly 20 to 40% of patients with MS do not have significant disability 10 years after their diagnosis.
What's Involved with Diagnosis and Treatment of MS?
Diagnosis of MS involves a clinical exam by the physician (neurologist), as well as diagnostic tests such as a magnetic resonance imaging (MRI) of the brain and spinal cord. An evaluation of the cerebrospinal fluid (CSF) and certain blood tests may also take place. Most patients initially present with Relapsing Remitting MS (RRMS), meaning symptoms may come and go over time. Eventually, over half of these RRMS patients will advance into a progressive course, where symptoms worsen with no remission.
Treatment of MS involves three distinct components: treatment of the acute attack; prevention of future attacks; and treatment of symptoms such as bladder dysfunction or depression.
What is an MS Attack or Relapse?
According to the National Multiple Sclerosis Society, an MS attack is defined as the worsening of MS symptoms, and/or the appearance of new symptoms, which lasts at least 24 hours and is separated from a prior exacerbation by at least one month. These flare-ups may come and go; you may go for a year or more without symptoms.
You can tell you are having a flare up if MS symptoms get suddenly worse - for example, maybe your vision in one eye becomes blurred, or a numbness or tingling in your body may return. New symptoms can last days, weeks or months, but eventually subside in RRMS. Lack of rest, alcohol use, or hot weather can bring on flare-ups, so avoid these triggers.
More About RRMS and Its Symptoms
RRMS is the most common form of multiple sclerosis; about 85% of people are initially diagnosed with this form. Relapses (attacks) of worsening neurologic functioning are followed by periods of remission in which partial or complete recovery occurs. Some people with RRMS might have just one symptom, while others may have many.
Common symptoms include fatigue, weakness, numbness, vision problems, walking problems, bladder/bowel or sexual dysfunction, depression, and problems with thinking clearly. Less commonly, problems with speech, swallowing, or breathing may occur. The normal routines of daily life and work - and one's quality of life - can be interrupted.
What Treatment Options Are Available for RRMS?
Just over 20 years ago there were no drug treatment options for MS at all, but today there is a wide variety of FDA-approved medications. Disease modifying agents, such as beta interferons and newer oral drugs alter the immune system to slow disease progression and reduce attacks. Some treatments also shorten the course of an acute MS attack.
Additional medications may be added to control symptoms such as pain, bladder or bowel problems, difficulty with movement, or depression. Symptoms of MS may come and go, but they can be managed with medications and rehabilitation. MS is not considered life-threatening as most people will live a normal life-span.
Interferon Beta: First Approved Therapy for MS
Interferon beta was the first therapy to be approved for the treatment of relapsing-remitting MS. The interferon betas include Avonex, Betaseron, Extavia, Rebif, and all are approved for the relapsing forms of MS. Betaseron was first approved in 1993. Peginterferon beta-1a (Plegridy) was approved in 2014 and has a longer duration of action.
These drugs are given by injection, either by intramuscular or subcutaneous (under the skin) shots, and you can be taught to do this at home for convenience. In addition, some formulations come as a prefilled syringe or autoinjector pen, to ease administration. Injections are given as often as every other day to only once every two weeks, depending upon the specific drug and dosing directions.
Other Interferon Beta Side Effects
Allergic reactions, depression, and liver toxicity are more serious, but less common side effects with interferon beta. You'll need to have blood tests to monitor your liver function. Some patients may develop antibodies to interferon beta in their blood and become immune to treatment, which may lessen its effect and require a treatment change.
Be sure to discuss possible treatment side effects and their frequency with your healthcare provider. Not every patient experiences the same side effects at the same frequency. Some reactions, like flu-like symptoms, may be more common just at the beginning of treatment.
Copaxone and Glatopa: Other Possible First Line Agents
Teva's Copaxone, and Sandoz's Glatopa are both glatiramer products, also a disease-modifying agent for RRMS. Glatopa is a substitutable generic version of Copaxone and only available in the 20 mg/mL dose. The generic agent can save patients thousands of dollars.
Common side effects with glatiramer include: injection site reactions, flushing, chest pain, or post-injection reaction (anxiety, chest pain, heart palpitations, shortness of breath, throat constriction, flushing). Post injection side effects typically last 15-30 minutes, subside without treatment, and have no known long-term effects.
New Oral MS Medications
Interferon beta preparations or glatiramer may be the initial therapy chosen by many doctors. However, side effects and the inconvenience of injections are often problematic with these treatments, and new oral therapies now provide unique options for patients with RRMS. Gilenya (fingolimod) was the first FDA-approved oral treatment for MS in 2010. More recently, other oral therapies have become available: Aubagio (teriflunomide) in 2012 and Tecfidera (dimethyl fumarate) in 2013.
The following slides outline benefits and possible side effects with these newer oral agents.
Important Facts: Gilenya
Gilenya is thought to work by preventing white blood cells (lymphocytes) from getting into the central nervous system (CNS) and causing inflammation and damage to nerve cells.
Gilenya has been shown to cut relapses by 52% when compared in a one year study to using interferon beta-1a, and by 54% when compared to placebo over two years. In addition, at one year, 13% more patients on Gilenya were relapse-free when compared to interferon beta-1a. Gilenya has also been shown to slow disease progression and the number of brain lesions on an MRI. Gilenya is manufactured by Novartis.
Gilenya Side Effects
Common side effects with Gilenya may include headache, infection, elevated liver enzymes, diarrhea, and cough. Macular edema, a swelling of an area of the retina responsible for central vision has been reported, as well, but this is an uncommon side effect. Patients with a history of heart disease may not be able to use Gilenya. In 2012, Gilenya prescribing information was revised to require patients to be monitored with a heart ECG before and 6 hours after the first dose of Gilenya, in addition to hourly measurements of blood pressure and heart rate. If a patient stops taking Gilenya for more than 14 days after their first month of treatment, they will need to repeat this first dose monitoring observation. If treatment is stopped in the first 4 weeks of treatment, additional monitoring is also needed.
Important Facts: Aubagio
Aubagio works by decreasing inflammation, lowering the number of white blood cells in the CNS, and protecting nerves in MS. In clinical trials, when the 14 mg oral dose of Aubagio was compared with placebo, a significant decrease in the three measures of MS activity - relapses (31% decrease), disability progression (30% decrease), and MRI brain lesions (80% decrease) - was shown. The manufacturer of Aubagio, Genzyme, warns not to take Aubagio if you have severe liver problems, are pregnant or are of childbearing age and not using effective birth control, or take a medication called leflunomide (Arava), a drug used in rheumatoid arthritis.
Aubagio Side Effects
Common side effects with Aubagio include headache, thinning hair (alopecia), diarrhea, nausea, elevated liver tests, flu-like symptoms and numbness or tingling in the hands or feet (paresthesias). Liver damage, increased risk for infections, and elevated blood pressure are other less common but more serious side effects. You will require regular blood tests to monitor liver function and blood cell counts. Aubagio can also cause severe birth defects, and neither women nor men should use Aubagio if a pregnancy is planned. Aubagio effects may remain in the body for 2 years after discontinuing therapy and special treatment to remove the drug may be required. Use of adequate methods of contraception by both females and males is recommended during and for 2 years after stopping treatment.
Important Facts: Tecfidera
Exactly how Tecfidera works in MS is not fully understood, but it does activate a chemical pathway in the body that helps to protect nerve cells from damage and inflammation. Tecfidera has been shown in clinical trials to have positive benefits in MS similar to other treatments: it reduces relapses, helps to delay physical disability progression, and lowers the number of brain lesions. Over a 2-year study, 27% of people taking Tecfidera experienced relapse compared with 46% of people taking placebo. In addition, 38% fewer people had disability progression compared to those taking placebo, and from 72-90% of MRI brain lesions slowed down in development.
Tecfidera Side Effects
Tecfidera appears to be tolerable from a side effect standpoint; common side effects include flushing (redness, itching and rash), diarrhea, stomach pain, and nausea; these effects tend to occur at the beginning of treatment and may subside over time. Taking Tecfidera with food may help to reduce the flushing.
A simple blood test will be performed prior to treatment and regularly thereafter to monitor the white blood cell count. If a serious infection develops, the provider may withhold treatment until resolved. Tecfidera is taken orally two times a day and is manufactured by Biogen Idec.
Tysabri, Lemtrada and Zinbryta: For Advancing MS
Tysabri is given every 4 weeks by IV infusion, and can be associated with a rare, but often fatal brain disease known as progressive multifocal leukoencephalopathy (PML). Lemtrada has a unique dosing schedule of two annual IV infusion treatments, but contains a boxed warning for serious side effects: autoimmune conditions, infusion reactions, and risk of cancer. Zinbryta is given once monthly by self-injection but can have serious liver side effects. All 3 drugs require a REMS restricted access program.
For More Advanced MS: Other Options
Mitoxantrone, a cancer drug available generically since 2006, may be considered for patients with worsening RRMS, progressive-relapsing MS, or secondary-progressive MS to help reduce the number of flare-ups and to lessen disability. Mitoxantrone is given 4 times a year by IV infusion in a medical clinic; heart function must be tested regularly. Common side effects may also include stomach upset and fatigue. Don't be surprise - mitoxantrone turns the urine a blue-green color temporarily for 1 to 2 days. The total lifetime dose is limited due to potential heart damage.
Mitoxantrone also has the potential for other serious side effects such as acute myelogenous leukemia and serious infections.
Do Disease-Modifying Drugs Help With MS Symptoms?
Not really. Disease-modifying drugs may not help you feel better once an attack begins - but they work to help reduce the chances for an MS attack and to slow progression of the disease. Attacks themselves often require different treatments.
For example, corticosteroids like oral prednisone or IV methylprednisolone (Solu-Medrol) may be used to reduce inflammation. Plasma exchange (plasmapheresis) has been used to treat severe symptoms in patients who do not respond to corticosteroids.
Ampyra is an oral potassium channel blocker from Acorda Therapeutics, Inc. approved in 2010. Ampyra (dalfampridine) is an MS medication shown to improve walking in those with MS, but you should not use this drug if you have a history of seizures or kidney disease. Ampyra, when given at doses greater than that recommended (10 milligrams twice a day), can cause seizures.
Investigational MS Agents on the Horizon
There are several investigational drugs in late-phase studies for the treatment of patients with relapsing or progressive multiple sclerosis. They cover a variety of mechanisms of action, and have demonstrated encouraging results in clinical trials.
Ocrelizumab (Genentech, Inc.)
Ocrelizumab is a humanized monoclonal antibody designed to target CD20-positive B-cells, which are implicated in the inflammatory and neurodegenerative processes of multiple sclerosis. It is a slightly modified version of Genentech's Rituxan (rituximab), which faces market competition from biosimilars. In February 2016, ocrelizumab was granted Breakthrough Therapy designation from the FDA for primary-progressive multiple sclerosis. A decision on approval is expected from the FDA by March 28, 2017.
Laquinimod (Teva Pharmaceutical Industries Ltd. and Active Biotech)
Laquinimod is an oral, CNS-active immunomodulator that combines anti-inflammatory and possibly neuroprotective effects. It is being studied for the treatment of relapsing-remitting multiple sclerosis (RRMS) and primary-progressive multiple sclerosis (PPMS). In Jan. 2016, Teva announced discontinuation of higher doses of laquinimod in two studies in MS after the occurrence of non-fatal heart-related events in eight patients. Studies are continuing in the lower-dose arms.
More Investigational Agents
Ozanimod (Celgene Corporation)
Ozanimod is an oral selective sphingosine 1-phosphate (S1P) 1 and 5 receptor modulator which works by reducing white blood cell migration to areas of inflammation. It is being studied to reduce relapses and delay disability progression in patients with relapsing forms of multiple sclerosis. Gilenya (fingolimod) was the first approved sphingosine 1-phosphate receptor modulator. Other S1P receptor modulators in clinical development include Novartis' siponimod and Actelion's ponesimod.
Anti-LINGO-1, or opicinumab, is an antibody which targets LINGO, a neurologic protein that is involved in the development of myelin. Anti-LINGO-1 is intended to stimulate regrowth of the myelin sheath, potentially allowing for the re-myelination and restoration of nerve communication in MS patients. Studies are ongoing, but primary and secondary endpoints have been missed in some Phase 2 studies.
A Must: A Healthy Lifestyle for MS Patients
There are lifestyle behaviors and trigger avoidances that can make multiple sclerosis more manageable - all MS patients should strive towards these goals while working in conjunction with their physicians, nurses, pharmacists, physical therapists, and other healthcare providers:
- Physical therapy
- Avoid extreme heat or cold
- Eat a healthy, balanced diet
- Don't smoke and avoid second-hand smoke
- Learn about your various medications
- Exercise regularly
- Reduce Stress
- Find emotional support
What About the Costs of MS Treatment?
Many treatments for multiple sclerosis are extremely costly, often running $30,000 to $50,000 per year. However, you may be able to get help to pay for your medications if you do not have adequate insurance coverage. Each pharmaceutical company may be able to offer assistance in applying for state and federal programs, and they might also offer direct patient assistance programs. If you do have insurance, be sure to check with your plan to determine their preferred treatments for MS, and the amount of your copay or co-insurance. You will most likely be referred to a specialty pharmacy that can help you with all drug-related issues.
Plus, don't forget to discuss your financial situation with your doctor and pharmacist who may have advice on medication cost-savings or new generic approvals.
How Do You Determine Which Treatment is Right?
Multiple sclerosis is a complicated condition that requires individualized attention and treatment from a dedicated team of healthcare providers. Decisions about drug treatment are made by weighing your individual factors, for example, your lifestyle, MS history, work and home-life considerations, and the side effect profiles of your treatment options.
Over time, you will want to continue these discussions with your healthcare provider as your condition and treatments evolve. Each person responds to MS treatments in different ways, so a personalized approach is the best way to forge a positive outcome.
While you and your doctor should only direct your medical treatment, consider joining the Drugs.com MS Support Group to ask questions, express concerns, and keep up with the latest news.
Finished: Multiple Sclerosis: What's New in MS Treatment Options?
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