Multiple Sclerosis: What's New in MS Treatment Options?
Medically reviewed on Apr 27, 2018 by L. Anderson, PharmD.
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)
RRMS is the most common form of MS, with periods of worsening (also called relapses, flare-ups, or exacerbations) and full recovery (remissions).
SPMS usually develops over time and follows RRMS; relapses can occur, but not remissions.
In PPMS, there is no eventual recovery - symptoms slowly worsen with no distinct relapses or remissions.
In PRMS, the disease progresses with intermittent relapses, but no remissions.
Am I at Risk for Multiple Sclerosis?
Anyone can get MS, but it occurs most frequently in white women 20 to 40 years old. In fact, young adults are most at risk, but it can occur in young children and older adults, too.
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 risk for MS is greater if you have a strong family history. 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?
A neurologist will typically diagnose multiple sclerosis.
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
- treatment of symptoms such as bladder dysfunction or depression.
What is an MS Attack or Relapse?
Early multiple sclerosis (MS) is often characterized by specific attacks or relapse, which may be followed by periods of remission.
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
- Hot weather
can bring on flare-ups, so avoid these triggers.
More About RRMS and Its Symptoms
Relapsing-Remitting MS (RRMS) is the most common form of multiple sclerosis; a large majority 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 you might have with RRMS include:
- vision problems
- walking problems
- bladder/bowel or sexual dysfunction
- 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:
- bladder or bowel problems
- difficulty with movement
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.
Beta Interferon: First Approved Therapy for MS
Beta interferon was the first therapy to be approved for the treatment of relapsing-remitting MS (RRMS).
The beta interferons include:
and all are approved for the relapsing forms of MS.
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.
Beta Interferon Side Effects
Side effects with interferons can be difficult, and may make you less likely to finish treatment.
- Flu-like symptoms and injection-site reactions are common with interferons.
- 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 beta interferon in their blood and become immune to treatment, which may lessen its effect and require a treatment change.
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.
Be sure to discuss possible treatment side effects and their frequency with your healthcare provider.
Copaxone and Glatopa: Possible First Line Agents
Glatopa is a substitutable generic version of Copaxone and only available in the 20 mg/mL dose. The generic agent may save you thousands of dollars.
Common side effects with glatiramer include:
- injection site reactions
- chest pain
- post-injection reaction (anxiety, chest pain, heart palpitations, shortness of breath, throat constriction, flushing).
Injection side effects typically last 15 to 30 minutes, subside without treatment, and have no known long-term effects.
New Oral MS Medications
Beta interferon preparations or glatiramer (Copaxone) may be the initial multiple sclerosis (MS) 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.
Other oral therapies that have become available since Gilenya include:
The following slides outline benefits and possible side effects with these oral agents.
Important Facts: Gilenya (fingolimod)
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 in clincial studies to cut relapses by over half when compared in a one year study to using interferon beta-1a, or 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.
According to the 2018 American Academy of Neurology guidelines, clinicians should prescribe fingolimod for people with highly active MS.
Gilenya Side Effects
Common side effects with Gilenya may include:
- elevated liver enzymes
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.
First -Dose Monitoring
Patients with a history of heart disease may not be able to use Gilenya; initiation of treatment can lead to a decrease in heart rate (bradycardia). 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 pulse. Additional monitoring may be needed based on specific circumstances outlined in the labeling.
Reinitiation of Therapy Following Discontinuation
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 within the first 4 weeks of treatment, additional monitoring is also needed as outlined in the product label.
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
- take a medication called leflunomide (Arava), a drug used in rheumatoid arthritis
- hypersensitivity reaction (severe allergy) to teriflunomide (Aubagio), leflunomide (Arava), or to any of the inactive ingredients in Aubagio
Aubagio Side Effects
Common side effects with Aubagio include:
- thinning hair (alopecia)
- elevated liver function tests
- flu-like symptoms
- 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 Use in Pregnancy
- Aubagio can lead to severe birth defects. There are specific directions that women of reproduction potential and men should follow.
- Neither women nor men should use Aubagio if a pregnancy is planned. Exclude pregnancy prior to starting treatment with Aubagio.
- Women of reproductive potential need effective birth control during Aubagio treatment and until completion of an accelerated elimination procedure to remove Aubagio from the body. An an accelerated elimination procedure can be used at any time after stopping Aubagio.
- If a woman suspects pregnancy, she should inform her doctor immediately.
- Aubagio is detected in human semen. Men taking Aubagio and not wishing to father a child should use effective contraception to minimize risk to the fetus; their female partners should also use effective contraception.
- Men who take Aubagio and wish to father a child should stop Aubagio and undergo an accelerated elimination procedure.
Aubagio effects may remain in the body for 2 years after discontinuing therapy and special treatment to remove the drug may be required. If Aubagio is discontinued, use of contraception should be continued until is it verified that plasma concentrations of teriflunomide are less than 0.02 mg/L (0.02 mcg/mL).
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
- 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% to 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)
- stomach pain
These side 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 manufactured by Biogen Idec.
Tysabri, Lemtrada: 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). Clinicians may initiate natalizumab treatment in people with MS with positive anti-JCV antibody indexes above 0.9 only when there is a reasonable chance of benefit compared with the low but serious risk of PML, based on 2018 American Academy of Neurology guidelines.
Other drugs that may be associated with PML include: fingolimod (Gilenya), rituximab (Rituxan), ocrelizumab (Ocrevus), and dimethyl fumarate (Tecfidera).
Natalizumab may also be linked with antibodies in people with MS and may lead to allergies or to reduced effectiveness of the medication. Stopping natalizumab results in an increased risk of MS relapse or MRI-detected disease activity within six months of discontinuation; however, switching to other agents may be possible.
Lemtrada has a unique dosing schedule of two annual IV infusion treatments, but contains a boxed warning for serious side effects, including:
- autoimmune conditions
- infusion reactions
- risk of cancer.
According to the 2018 American Academy of Neurology guidelines, clinicians should prescribe natalizumab or alemtuzumab for people with highly active MS.
Zinbryta (daclizumab) was used to treat relapsing forms of multiple sclerosis. However, in March 2018, Biogen and AbbVie announced the voluntary worldwide withdrawal for Zinbryta for relapsing multiple sclerosis due to serious adverse events.
For More Advanced MS: Other Options
Mitoxantrone, a cancer drug available generically since 2006, is an option for patients with worsening RRMS, progressive-relapsing MS, or secondary-progressive MS to help reduce the number of flare-ups and to lessen disability. However, the American Academy of Neurology in 2018 noted that because of the high frequency of severe side effects, clinicians should not prescribe mitoxantrone to people with MS unless the potential therapeutic benefits greatly outweigh the risks.
Possible severe side effects include:
- a high risk of cardiomyopathy (heart damage)
- ovarian failure
- male infertility
- chromosomal aberrations
- promyelocytic leukemia
Mitoxantrone is given 4 times a year by IV infusion in a medical clinic, and heart function must be tested regularly. The total lifetime dose is limited due to potential heart damage.
Common side effects may also include stomach upset and fatigue.
Ocrevus: First Treatment for Primary Progressive MS
Ocrevus (ocrelizumab) from Genentech was approved in March 2017.
Ocrevus is a monoclonal antibody that selectively targets CD20-positive B cells. It is the first treatment approved for primary progressive multiple sclerosis (PPMS); it’s also indicated for relapsing disease (RMS). Ocrevus is given as an intravenous (IV) infusion into a vein.
In 2018 guidelines, the American Academy of Neurology stated that clinicians should offer ocrelizumab to people with PPMS who are likely to benefit from this therapy unless there are risks of treatment that outweigh the benefits.
In both forms of MS, Phase III studies indicated that Ocrevus slowed disability and reduce signs of disease activity in the brain (MRI lesions). In the RMS group, annual relapses were lowered by nearly one-half.
Mild to moderate side effects include:
- infusion reactions
- respiratory tract 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 to start and to slow progression of the disease. Attacks themselves often require different treatments.
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 some, but not all, clinical trials.
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.
- In May 2017, Teva and Active Biotech announced that the CONCERTO trial of laquinimod in RRMS did not meet its primary endpoint, and RRMS studies will not be continued. However, Teva continues to evaluate the potential of laquinimod in primary progressive MS (PPMS) and Huntington disease (HD).
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-1, a CNS-specific protein that is involved in the development of myelin. In patients with MS, LINGO-1 may block myelin growth when it binds to receptors.
- 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.
- Phase 2 studies are ongoing with Biogen, but primary and secondary endpoints have been missed in some Phase 2 studies. In June 2016, Biogen reported from the SYNERGY placebo-controlled trial that anti-LINGO-1 had failed to improve measures of physical and cognitive function, or disability.
- However, in 2017, Biogen started another phase 2 trial looking at 240 patients with RMS on disease-modifying therapy. The study aims to see if anti-LINGO-1 slows worsening of disability in relapsing MS. The trial runs through 2020.
A Must: A Healthy Lifestyle for MS Patients
There are lifestyle behaviors and trigger avoidances that can make multiple sclerosis (MS) 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
Ask your doctor for the latest vitamin D information in MS. Several clinical trials are now testing vitamin D against MS. One small study of only 40 people has shown that high dose vitamin D (~10,000 IU per day) for six months reduced immune cells linked to relapsing MS. A clinical effect, like slowing progression or reducing relapses, was not evaluated.
Plus, a another study suggests (but does not prove) that newborns with low levels of vitamin D may be at greater risk of developing multiple sclerosis (MS) later in life.
What About the Costs of MS Treatment?
Many treatments for multiple sclerosis (MS) are extremely costly, often running $30,000 to $50,000 per year. However, you may be able to get help paying for your medications if you do not have adequate insurance coverage.
- Each pharmaceutical company may be able to 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
- Side effect profiles and costs 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 make decisions about your medical treatment, consider joining the Drugs.com MS Support Group to ask questions, express concerns, and keep up with the latest medical news.
Finished: Multiple Sclerosis: What's New in MS Treatment Options?
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- National Multiple Sclerosis Society. What is MS. Accessed May 10, 2018 at https://www.nationalmssociety.org/What-is-MS