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How to Manage the Side Effects of a New RRMS Medication

Written by Sherman Jia, MD on April 26, 2017
relapsing-remitting multiple sclerosis

All relapsing-remitting multiple sclerosis (RRMS) disease-modifying therapies suppress or modulate your immune system. As a result, they may increase the risk infection. However, with proper screening and monitoring, these medications can be used safely and significantly reduce MS attacks.

Here are the most common side effects associated with MS therapies, and effective ways for you to manage these side effects.

Injectable medications

These may cause injection-site reactions, such as redness, soreness, or itching, due to local inflammation. Rarely, an injection may cause an allergic reaction. In that case, you should seek immediate medical attention.

Interferon-beta-1a, peginterferon-beta-1a, and interferon-beta-1b

Interferon-beta-1a (Avonex, Rebif), peginterferon-beta-1a (Plegridy), and interferon-beta-1b (Betaseron, Extavia) commonly cause flu-like symptoms, including:

  • fever
  • chills
  • sweating
  • muscle aches
  • headaches
  • fatigue

These symptoms may last up to 24 to 48 hours after each dose. Although they usually go away on their own, they can be minimized by:

  • warming the medication to body temperature
  • administering treatment at night so symptoms occur during sleep
  • staying hydrated
  • maintaining good nutrition
  • using nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil) or naproxen (Aleve, Naprosyn)

Depressed mood can be exacerbated by interferon therapy. So it’s important to speak with your neurologist about the benefits and risks of staying on interferons, and whether you should start treatment for depressed mood.

Because interferons commonly cause elevations in liver enzymes, you should consume alcohol only in moderation. Screening for possible liver injury is important, especially in the first six months of therapy.

Glatiramer acetate

Glatiramer acetate (Copaxone, Glatopa) may cause transient flushing, palpitations, chest discomfort, or shortness of breath. These symptoms usually resolve on their own within minutes. However, you should seek medical attention if they are severe or persistent.

Repeated injections may cause cosmetic effects due to local loss of fat tissue (lipoatrophy). This can be prevented by rotating injection sites in your arms, abdomen, hips, and thighs. Overall, glatiramer acetate is one of the most commonly used and safest MS therapies available.

Daclizumab

Daclizumab (Zinbryta) is an effective RRMS therapy, but is less frequently used as a first-line agent due to uncommon but potentially serious side effects. Daclizumab causes twice as many serious infections compared to interferon therapy (4 percent vs. 2 percent) and twice as many injection site reactions (including some serious enough to discontinue the drug). Nonserious infections are also common (50 percent to 65 percent), primarily upper respiratory infections.

Significant elevated liver enzymes have been reported, so alcohol should be consumed only in moderation, and liver enzymes need to be checked monthly.

If you experience these side effects, discuss them with your MS neurologist to determine if this is the best treatment for you. With proper monitoring, daclizumab can be a safe and effective therapy for those with RRMS.

Oral medications

Oral medications for RRMS are considered more convenient compared to injectable therapies, and may be suitable for those who are used to taking daily medicines. Each of the three oral therapies are effective but may cause transient side effects that improve with time. In addition, proper monitoring and screening is needed prior to starting an oral therapy.

Fingolimod

Fingolimod (Gilenya) is a daily oral medication. Screening is required to ensure safety prior to the first dose. An eye exam is performed to screen for macular edema. Cardiac monitoring is performed for at least six hours after you take the first dose to screen for slowed heart rate.

This medication may cause airway reactivity, so it isn’t recommended to those with asthmas or bronchitis.

It may cause mild elevations in blood pressure, so eating a balanced diet low in sodium and exercising regularly are recommended.

Other side effects such as headaches, gastrointestinal symptoms, and elevated liver enzymes often improve over days to weeks. As always, discuss significant side effects with your MS neurologist.

Teriflunomide

Teriflunomide (Aubagio) is a daily oral therapy. It isn’t recommended for men or women who are planning to have children while on therapy, due to risk of birth defects. As with other RRMS medications, it’s recommended that sexually active women take birth control when on therapy.

Teriflunomide may cause gastrointestinal side effects such as:

  • abnormal liver enzymes
  • diarrhea
  • nausea

These tend to be mild to moderate and aren’t persistent. Drinking alcohol in moderation is recommended.

Some people (10 to 13 percent) experience mild hair thinning after taking this medication two to three months. However, most (86 percent) of them report complete or near-complete resolution months later.

Most side effects associated with teriflunomide resolve on their own, making this a reasonable option for those who aren’t planning pregnancy.

Dimethyl fumarate

Dimethyl-fumarate (Tecfidera) is a twice-daily therapy. It commonly causes flushing in the first few months of therapy, which can be minimized by taking the drug 30 minutes after consuming high-fat foods, such as peanut butter or avocado. Alternatively, taking 81 or 325 milligrams of aspirin may reduce symptoms of flushing.

Some also experience nausea, diarrhea, and abdominal discomfort in the first few weeks to months of treatment. These symptoms improve over time, but if they are severe, speak with your doctor about medications — for example, proton-pump inhibitors and antinausea or anti-diarrhea drugs — to manage these symptoms.

In addition, blood tests are performed every six months to screen for low white blood cell counts.

Intravenous Infusions

These infusions are given at a dedicated infusion center or specialized clinic. Patients are given pretreatment to minimize infusion-related reactions, and monitored after the treatment to ensure they tolerated the treatment without significant side effects. Regular blood monitoring is a key part of safety for those receiving infusion therapy.

Natalizumab

Natalizumab (Tysabri) is a monthly infusion therapy. Natalizumab increases the chance for a rare but serious brain infection called progressive multifocal leukoencephalopathy (PML) in those who test positive for the John Cunningham virus antibody. As a result, those taking this therapy require a blood test every three to six months, and should switch to another therapy if they test positive for this antibody.

Headache is a common side effect of natalizumab, and can usually be managed with over-the-counter pain medications such as ibuprofen.

In addition, you may experience urinary or lung infections, which should be discussed with and treated by a physician.

Mitoxantrone

Mitoxantrone (Novatrone) is an infusion given every three months. Common side effects include gastrointestinal symptoms (nausea, diarrhea), menstrual cycle disturbances in women, and urinary tract infections. If these side effects are persistent, you should discuss them with your MS neurologist to weigh the risks and benefits of continuing therapy.

Rare but serious side effects include a risk for injury to the heart (resulting in congestive heart failure), and a risk for a blood cancer called acute myeloid leukemia in those who are chronically treated with mitoxantrone. For these reasons, mitoxantrone is usually not the first-line therapy prescribed for treatment of RRMS.

Ocrelizumab

Ocrelizumab (Ocrevus) is the newest therapy for RRMS (and PPMS) approved by the U.S. Food and Drug Administration. It’s given once every six months. The most common side effects include infusion-related reactions, which are minimized with pretreatment at the infusion center.

A slightly higher occurrence of cancer was reported with ocrelizumab (0.5 percent) compared to interferon therapy (0.2 percent). However, it’s not clear if this a real trend. Overall, ocrelizumab has manageable side effects. However, more time is needed to see if it’s associated with additional serious side effects.

Alemtuzumab

Alemtuzumab (Lemtrada) is a therapy given for five consecutive days in one year, and for three consecutive days in the next year. Common side effects include infusion-related reactions, and secondary autoimmune disease (especially thyroid disease).

Rare but serious adverse events include serious infections and secondary malignancy (thyroid cancer, melanoma, and blood cancers). For these reasons, monthly blood tests are required for at least four years from the start of the first treatment, as well as an annual skin exams and an annual Pap smear for females.

The takeaway

The 15 FDA-approved RRMS therapies have a range of common and rare side effects. It’s important to understand potentially serious side effects before starting therapy. Always discuss the risks and benefits of a new RRMS therapy with your MS neurologist before proceeding with treatment. With proper guidance, it’s possible to receive effective treatment for RRMS while minimizing side effects.

Disclosure: At the time of publication, the author has no financial relationships with MS therapy manufacturers.

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