Multiple Sclerosis: Classifications and Disease-Modifying Therapies

Vocabulary flashcards covering the pathophysiology, clinical courses, monoclonal antibodies, oral agents, and injectable therapies used in the treatment of multiple sclerosis.

Multiple Sclerosis (MS)

An immune-mediated, inflammatory, neurodegenerative disease of the central nervous system that is a leading cause of disability in young adults.

Clinically Isolated Syndrome (CIS)

A first episode of neurologic symptoms like those of MS (commonly including bladder issues, vision problems, and difficulty with coordination, balance, walking, speaking, and swallowing) that is considered MS when certain criteria are met.

Relapsing-Remitting MS (RRMS)

The most common MS disease course, initially diagnosed in about $85\%$ of individuals, characterized by clearly defined attacks (relapses) followed by periods of partial or complete recovery (remission).

Secondary Progressive MS (SPMS)

A disease course that develops after an initial RRMS diagnosis, characterized by progressive decline in neurologic function and increasing disability over time, with possible relapses and periods of stability.

Primary Progressive MS (PPMS)

An MS disease course diagnosed in about $15\%$ of individuals where neurologic function worsens or disability accumulates from the onset of symptoms, lacking early relapses or remissions.

Monoclonal Antibodies

Laboratory-made immune proteins derived from a single B-cell clone that are engineered to bind specifically to one antigen target in the body.

Natalizumab

An integrin receptor antagonist indicated as monotherapy for relapsing forms of MS that blocks T-lymphocytes from crossing into the central nervous system.

Progressive Multifocal Leukoencephalopathy (PML)

A serious opportunistic brain infection associated with natalizumab and other DMTs, the risk of which correlates with JC polyomavirus (JCV) antibody levels.

Ocrelizumab

A recombinant humanized anti-CD20 monoclonal antibody that depletes CD20-expressing B cells, indicated for relapsing forms of MS and primary progressive MS (PPMS).

Rituximab

A chimeric mouse-human anti-CD20 monoclonal antibody used off-label for relapsing or active MS that induces B-cell reduction via complement-dependent cytotoxicity.

Ofatumumab

A human monoclonal antibody targeting CD20 on B lymphocytes that causes selective B-cell depletion, administered subcutaneously for relapsing forms of MS.

Ublituximab

A chimeric monoclonal antibody that targets CD20 on pre-B and mature B lymphocytes to cause B-cell lysis via complement-dependent and antibody-dependent cellular cytolysis.

Alemtuzumab

A humanized monoclonal antibody targeting CD52 to deplete T cells, B cells, natural killer cells, and monocytes; indicated for RRMS and active SPMS, but not recommended for CIS due to safety concerns.

Fumarates

A class of oral MS medications that exert neuroprotective and immunomodulatory effects via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway.

Dimethyl Fumarate

An oral fumarate available in $120\,\text{mg}$ and $240\,\text{mg}$ preparations, titrated up after seven days to a maintenance dose of $240\,\text{mg}$ twice daily, commonly causing flushing and GI upset.

Diroximel Fumarate

An oral fumarate initiated at $231\,\text{mg}$ twice daily for seven days, then maintained at $462\,\text{mg}$ twice daily; should not be taken with high-fat, high-calorie meals.

Monomethyl Fumarate

An oral fumarate initiated at $95\,\text{mg}$ twice daily for seven days and titrated to a maintenance dose of $190\,\text{mg}$ twice daily.

S1PR Modulators

A class of oral drugs that inhibit lymphocyte egress from lymph nodes, thereby preventing the migration of inflammatory cells into the central nervous system.

Fingolimod

An S1PR modulator dosed at $0.5\,\text{mg}$ once daily that requires a minimum of six hours of cardiac monitoring upon the first dose due to the risk of symptomatic bradycardia and AV block.

Siponimod

An S1PR modulator initiated at $0.25\,\text{mg}$ daily and titrated based on CYP2C9 genotyping; contraindicated in patients carrying the CYP2C93/3 genotype.

Ozanimod

An S1PR modulator titrated orally over seven days ($0.23\,\text{mg}$ on days 1–4, $0.46\,\text{mg}$ on days 5–7) to a maintenance dose of $0.92\,\text{mg}$ daily on day 8 and thereafter.

Ponesimod

An S1PR modulator initiated at $2\,\text{mg}$ daily and titrated over 15 days using a starter pack to a recommended maintenance dose of $20\,\text{mg}$ once daily.

Teriflunomide

An oral pyrimidine synthesis inhibitor dosed at $7\,\text{mg}$ or $14\,\text{mg}$ once daily that disrupts the interaction between T cells and antigen-presenting cells.

Accelerated Drug Elimination Procedure

An 11-day oral regimen using cholestyramine or activated charcoal powder to clear teriflunomide until plasma levels drop below $0.02\,\text{mg/L}$ before conception.

Cladribine

An oral purine antimetabolite targeting lymphocyte subtypes, administered at a cumulative dose of $3.5\,\text{mg/kg}$ divided across two yearly courses ($1.75\,\text{mg/kg}$ per course).

Interferons (IFNB)

Injectable cytokines that modulate immune responsiveness for treating RRMS; available as subcutaneous interferon beta-1b and intramuscular or subcutaneous interferon beta-1a.

Glatiramer Acetate (Copolymer 1)

A subcutaneous mixture of random four-amino-acid polymers mimicking myelin basic protein that induces Th2 suppressor cells to promote bystander suppression.