Comparison Review of MS Drugs

Disease-modifying therapies (DMTs) are currently the best way to prevent relapses and slow the disablity of multiple sclerosis (MS). There are several DMTs available on the market, which are listed below. When considering which treatment is best, each individual should talk to their doctor about the treatment options that are right for their unique situation, as well as all the potential benefits and risks of each treatment.¹

Treatment experiences can vary

MS is a disease that greatly varies in how it affects different people, the frequency and severity of relapses or exacerbations, the symptoms presented, and the rate of disease progression. How well a particular drug works in one person may be different from how well it works in another person. It is helpful to keep in mind these variations between people when considering which treatment to choose.

Considerations when choosing between different treatments

Common considerations when choosing between different treatments include:

• Cost
• Effectiveness at preventing new relapses
• Side effects/safety
• Route of administration

Cost of different MS treatments

Cost will vary based on each individual’s health insurance coverage and benefits. Several of the drug manufacturers have patient assistance programs that can also help cover the cost of medications.

MS treatment safety and effectiveness

All drugs that receive approval from the US Food and Drug Administration must undergo several controlled clinical trials to prove that the product is effective and safe. However, the degree of effectiveness at preventing relapses and the safety profile differ between DMTs. During some of these trials, new potential treatments may be compared to existing standard treatments, called head-to-head studies.²

Slowing down progression and reducing relapses

However, there is no one trial or source of information that compares all of the current DMTs to each other. All of the DMTs available have demonstrated through clinical trials that they reduce the frequency and severity of relapses in relapsing forms of MS, reduce the development of new MS lesions, and appear to slow down the disability progression.¹ Only one DMT, ocrelizumab (Ocrevus®), is approved for both relapsing forms and primary progressive MS (PPMS).³

Comparison by route of administration

Subcutaneous injections:

• Interferon beta-1a (Rebif®)
• Interferon beta-1b (Betaseron®)
• Interferon beta-1b (Extavia®)
• Glatiramer acetate (Copaxone®, Glatopa®)
• Peginterferon beta-1a (Plegridy®)
• Ofatumumab (Kesimpta®)

Intramuscular injection:

• Interferon beta-1a (Avonex®)
• Peginterferon beta-1a (Plegridy®)

IV infusions:

• Alemtuzumab (Lemtrada®)
• Mitoxantrone (Novantrone®)
• Natalizumab (Tysabri®)
• Ocrelizumab (Ocrevus®)
• Ublituximab (Briumvi®)

Oral medications:

• Cladribine (Mavenclad®)
• Dimethyl fumarate (Tecfidera®)
• Diroximel fumarate (Vumerity®)
• Fingolimod (Gilenya®, Tascenso ODT™)
• Ozanimod (Zeposia®)
• Siponimod (Mayzent®)
• Teriflunomide (Aubagio®)
• Monomethyl Fumarate (Bafiertam®)
• Ponesimod (Ponvory®)

Comparison by common side effects

All medications can cause unwanted side effects. However, not all patients experience the same side effects. The side effects listed below are not all the possible side effects that these medications may cause. Individuals should talk to their doctor about what to expect and report any concerns to their doctor.^4-19

• Alemtuzumab (Lemtrada®) – Rash, headache, fever, inflammation of the nasal passages and throat, nausea, vomiting, infection (urinary tract, upper respiratory tract, viral including herpes, fungal), fatigue, insomnia, red welts on skin, itching, thyroid gland disorders, joint pain, pain in arms or legs, back pain, mouth and throat pain, abdominal pain, diarrhea, sinus infection, tingling or prickling sensation, dizziness, flushing
• Cladribine (Mavenclad®) - Upper respiratory tract infection, headache, lymphopenia
• Dimethyl fumarate (Tecfidera®) – Flushing, abdominal pain, diarrhea, nausea
• Diroximel fumarate (Vumerity®) – Flushing (developing red or hot skin), redness, itching, or rash, nausea and vomiting, diarrhea, stomach pain or indigestion
• Fingolimod (Gilenya®) – Headache, diarrhea, increased liver enzymes, cough, flu-like symptoms, sinus symptoms, infections, back pain, abdominal pain, and pain in the arms and legs
• Glatiramer acetate (Copaxone®) – Reactions at the injection site, lowered blood pressure, rash, difficulty breathing, and chest pain
• Interferon beta-1b (Extavia®) – Reactions at the injection site, flu-like symptoms, low counts of white blood cells, muscle aches, increased liver enzymes, headache, spasticity, pain, rash, difficulty sleeping, abdominal pain, depression, joint pain, and weakness or lack of energy
• Interferon beta-1a (Avonex®) – Reactions at the injection site, flu-like symptoms, low counts of white blood cells, muscle aches, increased liver enzymes, headache, spasticity, pain, rash, difficulty sleeping, abdominal pain, depression, joint pain, and weakness or lack of energy
• Interferon beta-1a (Rebif®) – Reactions at the injection site, flu-like symptoms, low counts of white blood cells, muscle aches, increased liver enzymes, headache, spasticity, pain, rash, difficulty sleeping, abdominal pain, depression, joint pain, and weakness or lack of energy
• Interferon beta-1b (Betaseron®) – Reactions at the injection site, flu-like symptoms, low counts of white blood cells, muscle aches, increased liver enzymes, headache, spasticity, pain, rash, difficulty sleeping, abdominal pain, depression, joint pain, and weakness or lack of energy
• Mitoxantrone (Novantrone®) – Nausea, hair loss, urinary tract infection, menstrual disorders (including amenorrhea), weakness or lack of energy
• Natalizumab (Tysabri®) – Headache, fatigue, joint pain, urinary tract infection, lower respiratory tract infection, inflammation in the stomach, vaginal infection, depression, pain in arms or legs, abdominal discomfort, diarrhea, rash
• Ocrelizumab (Ocrevus®) – Infusion-related reactions and upper respiratory tract infections
• Ozanimod (Zeposia®) – Upper respiratory infection, urinary tract infection, liver function changes, high blood pressure or changes in blood pressure when standing up (orthostatic hypotension), back pain
• Peginterferon beta-1a (Plegridy®) – Flu-like symptoms, headache, injection site reactions, blood count abnormalities, asthenia (feeling weak or tired), abdominal pain, diarrhea, nausea and vomiting, myalgia (muscle or joint pain), infections
• Siponimod (Mayzent®) – Headache, high blood pressure, increased liver enzymes
• Teriflunomide (Aubagio®) – Headache, diarrhea, nausea, hair loss, increased liver enzymes

Comparison by safety concerns

While rare, DMTs may cause serious side effects. Not everyone who takes these medications experiences serious side effects. Individuals should discuss all safety concerns with their doctor prior to beginning treatment with a DMT.^4-19

• Alemtuzumab (Lemtrada®) – Infusion-associated reactions and severe allergic reaction, rare viral disease (progressive multifocal leukoencephalopathy), development of secondary or new autoimmunity including thyroid autoimmune disorders, increased risk of certain cancers, infections (including opportunistic such as herpes virus, human papilloma virus, fungal infections, listeria, and nocardiosis)
• Cladribine (Mavenclad®) – Increased risk of infections and malignancies, worsening of chronic infections such as HIV, hepatitis or TB, fetal harm.
• Dimethyl fumarate (Tecfidera®) – Severe allergic reaction, lowered white blood cell counts, liver injury, rare viral disease (progressive multifocal leukoencephalopathy), swelling (angioedema) in the face, tongue, throat, abdomen, hands or feet
• Diroximel fumarate (Vumerity®) – Allergic reactions including welts and hives, PML (progressive multifocal leukoencephalopathy – a rare brain infection, shingles, decrease in white blood cell count, severe liver problems
• Fingolimod (Gilenya®) – Change in heart rhythm that may cause sudden death, increased risk of infections, rare viral disease (progressive multifocal leukoencephalopathy), increased fluid in the retina (macular edema), posterior reversible encephalopathy syndrome, respiratory effects, liver injury, risk of causing birth defects, increased blood pressure, basal cell carcinoma
• Glatiramer acetate ( Copaxone®) – Post-injection reaction (rapid heartbeat, anxiety, throat constriction)
• Interferon beta-1a (Avonex®) – Liver damage, severe allergic reaction, depression (and suicidal thoughts), congestive heart failure, seizures, autoimmune disorders, leukopenia thrombotic microangiopathy, decreased peripheral blood counts
• Interferon beta-1a (Rebif®) – Liver damage, severe allergic reaction, depression (and suicidal thoughts), congestive heart failure, seizures, autoimmune disorders, leukopenia thrombotic microangiopathy, decreased peripheral blood counts
• Interferon beta-1b (Betaseron®) – Liver damage, severe allergic reaction, depression (and suicidal thoughts), congestive heart failure, seizures, autoimmune disorders, leukopenia thrombotic microangiopathy, decreased peripheral blood counts
• Interferon beta-1b (Extavia®) – Liver damage, severe allergic reaction, depression (and suicidal thoughts), congestive heart failure, seizures, autoimmune disorders, leukopenia thrombotic microangiopathy, decreased peripheral blood counts
• Mitoxantrone (Novantrone®) – Congestive heart failure (can result in death) may occur either during or months to years after termination of therapy. Secondary acute myeloid leukemia, infection, lowered white blood cell counts, depression, vomiting, kidney failure
• Natalizumab (Tysabri®) – Rare viral disease (progressive multifocal leukoencephalopathy), severe allergic reactions, suppression of the immune system, increased risk of infections (including herpes simplex virus, meningitis), and liver injury
• Ocrelizumab (Ocrevus®) – Infusion-related reactions, increased risk of infections, increased risk of certain cancers
• Ozanimod (Zeposia®) – Change in heart rhythm, increased risk of infections, liver damage, respiratory effects, macular edema, increased blood pressure
• Peginterferon beta-1a (Plegridy®) – Liver damage, severe allergic reaction, depression (and suicidal thoughts), congestive heart failure, seizures, autoimmune disorders, leukopenia thrombotic microangiopathy, decreased peripheral blood counts
• Siponimod (Mayzent®) – Macular edema, increased risk of infections, decrease in heart rate
• Teriflunomide (Aubagio®) – Liver injury, risk of causing birth defects, bone marrow effects, suppression of the immune system, increased risk of infections, peripheral neuropathy, skin conditions, increased blood pressure, respiratory effects, pancreatitis, lowered white blood cell counts