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Disease Modifying Therapies in MS

The following is a current chart of disease modifying therapies approved for the treatment of multiple sclerosis, as of November 2020. Reviewed by Rocky Mountain MS Center Medical Director Dr. Timothy Vollmer.

Class

Drug Names

General Dosing Info

Mechanism of Action

Effectiveness

Possibility of Improvement

Possible Side Effects

Interferons

Includes Betaseron®; Avonex®; Plegridy®; Rebif®; and Extavia®

All are injected and differ by dose and frequency of injection.

All work by decreasing ability of lymphocytes to enter the brain.

All only decrease relapses by 30%; does not prevent progressive MS; 0% effect on brain atrophy.

Very low

Depression, suicide, psychosis, liver toxicity, seizures, allergic reactions, congestive heart failure , i peripheral blood counts, thrombotic microangiopathy, flu-like symptoms common (49%).

Glatiramer Acetate

Copaxone® daily; Copaxone 3x/wk; Glatopa® daily; Mylan®3x/wk

All injected under the skin by the patient and differ by dose and frequency of injection.

Works by inducing a regulatory B cell specific for MS.

Only decrease relapses by 30%; does not prevent progressive MS; decrease brain atrophy 20%.

Low

Post-injection reaction (16%), transient chest pain (13%), lipoatrophy (localized loss of fat tissue), skin necrosis, injection-site reactions.

Teriflunomide

Aubagio®

Once a day oral medication.

Inhibits the ability of all lymphocytes to grow, leads to lymphocyte death including B lymphocytes.

30% decrease relapse rate; trend in slowing disability; decreases brain atrophy by 20%; Effects on disability and brain atrophy are not statistically significant.

Modest

Boxed warning* for hepatotoxicity (including fatal liver failure) and teratogenicity. i white blood cells , h risk of infection, peripheral neuropathy (1.4%-1.9%); h blood pressure (3%-4%); hair thinning

Dimethyl Fumerate

Tecfidera®; Generic dimethyl fumarate; Diroximel fumurate (Vumerity®); Monomethyl fumarate (Bafiertam®)

All are oral; differ in dose and frequency.

Inhibiting proinflammatory astrocytes.

Moderately effective:
decreases relapses by 50%; decreases MRI activity by 50%; decreases brain atrophy by 30%.

Moderate

Nausea, vomiting, abdominal pain, Anaphylaxis, angioedema, PML*** (rare), i white blood cells, flushing (40%).

Fingolimod

Gilenya®; Siponimod (Mayzent®); Ozanimod (Zeposia®); Generic fingolimod x 3

Daily oral medication (Gilenya – first dose given while being monitored for 6 hours in clinic). Ozanimod doesn’t require first dose monitoring. Ozanimod also does not require the genetic testing that Siponimod requires.

Inhibiting proinflammatory astrocytes.

Moderately effective:
decreases relapses by 60%; decreases MRI activity by 60-70%; decreases brain atrophy by 34%.

Moderately high

First-dose bradycardia, h risk of serious infection, PML***, macular edema, posterior reversible encephalopathy syndrome, i respiratory function, liver toxicity, h blood pressure , basal cell carcinoma, melanoma (2%). Only available through REMS**.

Alemtuzumab

Lemtrada®

5 days of IV infusion year 1 and 3 days IV infusion year 2.

Kills all cells expressing CD52 including B cells. Changes regulation of immune system.

Decreases brain atrophy 40%.

High

Boxed warning* for serious (sometimes fatal) autoimmune conditions which occur in up to 40% such as immune thrombocytopenic purpura which is a bleeding disorder, life-threatening infusion reactions, h risk of malignancies. Infusion reactions (92%), rash (53%), lymphopenia (99.9%). Only available through REMS**. Approved by FDA for rescue use only.

Cladribine

Mavenclad®

Oral chemotherapy medication with two treatment cycles.

Inhibits pro-inflammatory lymphocytes. Temporarily reduces the number of both T and B lymphocytes.

Decreases relapse rate by 58%; modest positive effect on disability progression and rate of brain volume loss.

Moderate

Boxed warnings* for risk of cancers and birth defects if used in pregnant woman. Approved by FDA for rescue use only.

Natalizumab

Tysabri®

Given intravenously once per month at infusion center.

Blocks ability of B cells to migrate into the brain.

Highly effective: decreases relapses by 67%; decreases MRI activity by 80%; decreases brain volume loss by 45%.

Very high

Boxed warning for PML***. h risk for herpes encephalitis and meningitis, liver toxicity, hypersensitivity (including anaphylaxis) reaction, h risk of infection. Only available through REMS**. Note: repeated negative testing for the JC virus that causes PML*** can dramatically minimize the risk of PML***.

Ocrelizumab/Ofatumumab

Ocrevus®; Kesimpta®

Once every 6 month infusion.

Selectively depletes circulating B cells.

Decreases relapse rate by 80%; decreases MRI disease activity by 95%; decreases brain atrophy by 45%.

Very high in RRMS

Infusion reactions, risk of infection, Hep B reactivation in Hep B positive patients, possible h risk for PML*** (1 case out of 170,000 treated to date).

 

* Boxed Warning: A black boxed warning is the FDA’s most stringent warning for drugs and medical devices on the market. Black box warnings, or boxed warnings, alert the public and health care providers to serious side effects, such as injury or death.

** REMS (Risk Evaluation and Mitigation Strategy):  REMS is a drug safety program that the U.S. Food and Drug Administration (FDA) can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks.

*** PML (Progressive Multifocal Leukoencephalopathy): PML is a rare but serious brain infection that is caused by the JC Virus (JCV). PML is seen in MS patients who are JC virus (JCV) positive and on disease modifying therapies known to increase the risk of PML. At least 50% of the general population has been exposed to JCV, but the infection is generally asymptomatic. But, in immunocompromised patients, including those taking certain MS DMTs, the JC Virus can infect the brain and result in PML. PML The first case of PML in MS was discovered in 2005 with the use of Tysabri.

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