In MS patients, the immune system attacks the protective coating around nerve fibers, called myelin, which causes inflammation and or destruction of nerve cells. The damaged areas of the central nervous system develop scar tissue, giving the disease its name and characteristic lesions visualized by MRI. As a result of these processes, electrical messages throughout the CNS are delayed or stopped completely, which results in various neurological symptoms.
Risk Factors for Development of MS
MS is not likely caused by one factor. Genetic and environmental factors and their combination predispose an individual to the disease. Genetic risk factors are related to autoimmune pathways.
Genetic Risk Factors
Female
Known MS in first degree relative increases chances by about 2-4%.
Monozygotic twin with MS gives incidence of 30-50% in the other.
200 known gene variants, the most notable being human leukocyte antigen DRB1*1501 haplotype
Environment Risk Factors
Geographical latitude, with temperate climates having more MS cases.
Low vitamin D levels.
Obesity
Exposure to tobacco products.
Mononucleosis infection (Epstein-Barr virus).
Viral infection from various viruses.
Trauma
Symptomatic Progression
MS progression is highly variable from one person to the next and its not correlated to risk factors. No treatment currently available completely halts its progression. Many patients have symptoms that persist with periods of remission that vary greatly in duration. After ten to twenty years, many MS patients develop progressive symptoms and impairments.
Common Initial Symptoms
Fatigue
Numbness
Blurry vision
Weakness
Progressive Symptoms
Loss of bladder control.
Impaired ambulation.
Slowed mental abilities
Treatment Options
Avonex (interferon beta-1a) dosed as 30 mcg intramuscularly weekly was approved in 1996 for relapsing forms of MS. Side effects include headache, flu-like symptoms (chills, fever, muscle pain, fatigue weakness), injection site pain and inflammation.
Betaseron ( interferon beta-1b) dosed as 0.25 mg subcutaneously every other day was approved in 1993 for relapsing forms of MS. Side effects include flu-like symptoms (chills, fever, muscle pain, fatigue, weakness) following injection, headache, injection site reactions (swelling redness, pain), injection site skin breakdown, and low white blood cell count.
Copaxone (glatiramer acetate) dosed as 20 mg subcutaneously every day or 40 mg subcutaneously three times per week was approved in 1996 for relapsing forms of MS. Side effects include injection site reactions (redness, pain, swelling), flushing, shortness of breath, rash, and chest pain.
Extavia (interferon beta-1b) dosed as 0.25 mg subcutaneously every other day was approved in 2009 for relapsing forms of MS. Side effects include flu-like symptoms (chills, fever, muscle pain, fatigue, weakness) following injection, headache, and injection site reactions (swelling redness, pain).
Glaterimer Acetate (therapeutic equivalent to Copaxone) dosed as 20 mg subcutaneously every day, or 40 mg subcutaneously three times per week was approved in 2017 for relapsing forms of MS. Side effects include injection site reactions (redness, pain, swelling), flushing, shortness of breath, rash, and chest pain
Glatopa (glatiramer acetate, generic equivalent of Copaxone) dosed as 20 mg subcutaneously every day, or 40 mg subcutaneously three times per week was approved in 2015 for relapsing forms of MS. Side effects include injection site reactions (redness, pain, swelling), flushing, shortness of breath, rash, and chest pain.
Plegridy (pegylated interferon beta-1a) dosed as 125 mcg subcutaneously every 14 days was approved in 2014 for relapsing forms of MS. Side effects include flu-like symptoms (chills, fever, muscle pain, fatigue, weakness, headache, itching), and injection site reactions (swelling, redness, pain).
Rebif (interferon beta-1a) dosed as 22 mcg or 44 mcg subcutaneously three times per week was approved in 1998 for relapsing forms of MS. Side effects include flu-like symptoms (chills, fever, muscle pain, fatigue, weakness, headache), and injection site reactions (redness, pain, swelling).
Aubagio (teriflunomide) dosed as a 7 mg or 14 mg pill once daily was approved in 2012 for relapsing forms of MS. Side effects include headache, hair thinning, diarrhea, nausea, and abnormal liver tests.
Gilenya (fingolimod) dosed as 0.5 mg capsule once daily was approved in 2010 for relapsing forms of MS. Side effects include headache, flu, diarrhea, back pain, abnormal liver tests, sinusitis, abdominal pain, pain in extremities, and cough.
Mavenclad (cladribine) dosed as a weight based tablet given in two treatment courses, once per year for two years. Each treatment course has two cycles, which are 4-5 days long and about one month apart. Approved in 2019 for relapsing forms of MS. Side effects include upper respiratory infection, headache, and low white blood cell count.
Mayzent (siponimod) dosed as a 1 or 2 mg pill once daily with increases each day over 4-5 days to the ongoing (maintenance) dose. Approved in 2019 for relapsing forms of MS. Side effects include headache, high blood pressure, and abnormal liver tests.
Tecfidera (dimethyl fumarate) dosed as a 120 mg capsule taken twice daily for one week, followed by 240 mg capsule taken twice daily thereafter. Approved in 2013 for relapsing forms of MS. Side effects include flushing (sensation of heat or itching and a blush on the skin), and gastrointestinal issues (nausea, diarrhea, abdominal pain).
Vumerity (diroximel fumarate) dosed as a 231 mg capsule taken twice daily for one week, followed by two 231 mg capsules taken twice daily thereafter. Approved in 2013 for relapsing forms of MS. Side effects include flushing (redness, itching, rash) and stomach problems (nausea, vomiting, diarrhea, stomach pain, indigestion).
Zeposia (ozanimod) dosed as a 0.23 mg capsule once daily for days 1-4, followed by 0.46 mg capsule once daily for days 5-7, then increased to 0.92 mg capsule once daily on day 8 and thereafter. Approved in 2020 for relasping forms of MS. Side effects include upper respiratory tract infections, elevated liver enzymes, low blood pressure when you stand up (orthostatic hypotension), painful and frequent urination (signs of urinary tract infection), back pain and high blood pressure.
Lemtrada (alemtuzumab) dosed as 12 mg intravenously per day for five consecutive days, followed by 12 mg per day on three consecutive days one year later. Approved in 2014 for relapsing forms of MS. Side effects include rash, headache, fever, nasal congestion, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infections, hives, itching, thyroid gland disorders, fungal infection, pain in joints, extremities and back, diarrhea, vomiting, flushing. Infusion reactions (including nausea, hives, itching, insomnia, chills, flushing, fatigue, shortness of breath, changes in the sense of taste, indigestion, dizziness, pain) are also common while the medication is being administered and for 24 hours or more after the infusion is over.
Novantrone (mitoxantrone) dosed as 12 mg/m² intravenously every 3 months. Lifetime cumulative dose limit of approximately 8-12 doses over 2-3 years. Approved in 2000 for reducing neurologic disability and/or the frequency of clinical relapses in adult patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting MS. Side effects include nausea, hair loss, menstrual change, upper respiratory infection, urinary tract infection, mouth sores, irregular heartbeat, diarrhea, constipation, back pain, sinusitis, headache, and blue-green urine.
Ocrevus (ocrelizumab) dosed as 600 mg intravenously every 6 months (first dose: 300 mg IV on day one and 300 mg IV 2 weeks later). Approved in 2017 for relapsing forms of MS. Side effects include infusion reactions (most commonly itchy skin, rash, throat irritation, flushed face or fever, headache), which in rare instances may be life-threatening; increased risk of infections, including respiratory tract infections and herpes infections; possible increase in malignancies, including breast cancer.
Tysabri (natalizumab) dosed as 300 mg intravenously once every 28 days in an approved infusion center. Approved in 2006 as a monotherapy for relapsing forms of MS. Side effects include headache, fatigue, joint pain, chest discomfort, urinary tract infection, lower respiratory tract infection, gastroenteritis, vaginitis, depression, pain in extremity, abdominal discomfort, diarrhea, and rash.
References
Disease-modifying Therapies for MS. Updated June 2020. NationalMSsociety.org/DMT. Accessed: November 21, 2020.
Brownlee WJ et al: Diagnosis of multiple sclerosis: progress and challenges. Lancet.389(10076):1336-46, 2017.
CMSC DMT Guideline Writing Group. 2019 CMSC Practical Guidelines for the Selection of Disease-Modifying Therapies in Multiple Sclerosis. Release Date: February 28, 2019. Doc.
