nihms-1613231

A common autoimmune demyelinating disease of the central nervous system.

Lancet.

MS refractory to at least two other treatments.

It evaluated pegylated interferon beta-1a for relapsing-remitting multiple sclerosis.

A randomised double-blind placebo-controlled study.

Incomplete recovery from relapses.

Recognition that B cells have a key role in pathogenesis, moving away from a purely T-cell-mediated model.

Interferon beta-1a in relapsing/remitting multiple sclerosis.

Early in the disease course to protect against late disability.

Insidious progression independent of relapse activity during the relapsing phase.

They are highly effective in preventing attacks and can partially protect against progression.

To guide the use of disease-modifying therapy in MS based on the authors’ practice pattern.

Attacks are abolished in most patients, but silent progression occurs during the relapsing phase.

≥1 T2 lesion on MRI in at least 2 out of 4 MS-typical regions of the CNS or awaiting a further clinical attack implicating a different CNS site.

By approximately one-quarter.

Anti-CD20 monoclonal antibody (mAb).

Suboptimal response, more than one relapse with active MRI scans in the prior year, and safety issues.

Sensory loss, unilateral painful visual loss, limb weakness, facial weakness, visual blurring, ataxia, vertigo, and fatigue.

The natural history of relapse-onset MS in the pretreatment era.

Secondary progressive multiple sclerosis.

≥2 attacks with objective clinical evidence of ≥2 lesions or 1 lesion with reasonable historical evidence of a prior attack.

Inhibiting lymphocyte access to the CNS or sequestering lymphocytes in primary lymphoid organs.

IV infusion, every 6 months.

Discontinuation of the therapies is required.

α4β1 integrin inhibitor.

Oligoclonal immunoglobulin and modest inflammation with mononuclear cells.

Seizure, dementia, and movement disorders.

Multiple Sclerosis (MS).

A multifaceted approach to control acute attacks, manage progressive worsening, and remediate symptoms.

Extended disability status score.

Simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing lesions or a new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI.

They are typically associated with relapses but also occur in patients who progress gradually without acute attacks.

Rituximab, ocrelizumab, and ofatumumab.

Infusion-related reaction, nasopharyngitis, upper respiratory tract infection, headache, and urinary tract infection.

A chimeric anti-CD20 monoclonal antibody.

It inhibits the α4β1 integrin, an adhesion molecule on lymphocytes.

48–60%.

Mild cognitive dysfunction, often referred to as 'brain fog', and difficulty with multitasking.

Relapsing or progressive.

They reduce the rate of relapses, accumulation of MRI lesions, and can stabilize or modestly improve disability.

29%.

33%.

Subcutaneous injection, every 2 weeks.

Injection-site erythema, influenza-like illness, pyrexia, and headache.

Lymphopenia, flu-like symptoms, and injection-site reactions.

Inflammation causing episodic attacks and neurodegeneration responsible for progressive worsening.

Diroximel fumarate.

Higher-efficacy drugs requiring less frequent administration.

≥1 T2+ lesions in the MS-characteristic periventricular, juxtacortical, or infratentorial regions.

It improves long-term outcomes.

They are due to gradual concentric expansion of chronic plaques, characterized by a rim of activated microglia, astrocytosis, stressed oligodendrocytes, and progressive axonal injury.

The development of highly effective therapies against progressive MS.

A mixture of random polypeptides composed of four amino acids.

It is a selective S1P modulator approved for relapsing forms of MS, including active SPMS.

The nuclear factor (erythroid-derived 2)–like 2 (Nrf2) pathway.

Highest in North America (>100 cases per 100,000) and lowest around the equator (<30 cases per 100,000).

Acute or subacute over hours to days, sometimes followed by gradual spontaneous remission.

Nasopharyngitis, headache, diarrhea, and alanine aminotransferase increase.

An autoimmune demyelinating and neurodegenerative disease of the central nervous system.

A randomised, phase 3, double-blind study.

Due to severe toxicities.

Clinically isolated syndrome.

Progressive multifocal leukoencephalopathy risk.

Perivenous inflammation dominated by lymphocytes and macrophages, demyelination with activated microglia, sharply demarcated plaques with glial scarring, and axonal loss.

It selectively depletes CD20-expressing B cells while preserving humoral immunity.

Glatiramer acetate can be continued during pregnancy.

Multiple lesions in white matter, particularly in cerebral hemispheres, brainstem, and spinal cord, with recent lesions enhancing with gadolinium.

Oral, once daily.

They reflect a highly focused immune response by activated B cells in the CNS.

A relapse-independent 'silent' progression.

Oral, once daily.

39%.

31%.

1. Inflammation with demyelination, and 2) Astroglial proliferation (gliosis) and neurodegeneration.

Interferons and glatiramer acetate.

Clinical trials showed they did not yield effective results.

Positive cerebrospinal fluid indicates isoelectric focusing evidence of oligoclonal bands and/or elevated IgG index.

47%.

Astrogliosis throughout the CNS white matter, decreased myelin density, and ongoing axonal damage.

68%.

Conduction delay in visual, auditory, and sensory pathways.

Flushing, diarrhea, nausea, upper abdominal pain, decreased lymphocyte counts, and elevated liver aminotransferase.

Gradual worsening after a decrease in the frequency of relapses.

Clinically Isolated Syndrome (CIS) and Relapsing Multiple Sclerosis (RMS), first line.

37%.

Severe treatment refractory disease unresponsive to high efficacy treatments.

Ocrelizumab.

Every 6–12 months.

As an intravenous infusion every 24 weeks.

Headache, diarrhea, nausea, alopecia, and increased hepatic alanine transferase.

Magnetic Resonance Imaging (MRI).

Fatigue and allergic reaction.

Approximately 0.4%.

Bradycardia, atrioventricular conduction block, macular edema, elevated liver enzyme levels, and mild hypertension.

Objective evidence of inflammatory CNS injury and details of dissemination in space and time.

It indicates a breakdown in the blood-brain barrier and is a marker of acute inflammation.

RMS has a mean age of onset of ~30 years, while PPMS has ~40 years.

Dihydroorotate dehydrogenase inhibitor.

Subcutaneous injection, once daily or 3 times weekly.

Use of higher-efficacy drugs as first-line treatment before permanent disability is evident.

T cells play a critical role in the pathogenesis of CNS autoimmune diseases.

Highly effective disease-modifying therapies are now recommended as first-line options instead of traditional treatments like high-dose IFN β −1a and glatiramer acetate.

They are found in the meninges, often in deep sulci, with underlying cortical demyelination and neuronal loss.

It is highly effective against relapses and silent progression, and halts new white matter lesions.

Effective treatment of progression.

It is an S1P inhibitor that prevents lymphocyte egress from secondary lymphoid organs.

48–53%.

A periventricular distribution of lesions and lesions in juxtacortical white matter, infratentorial white matter, and spinal cord.

They have lengthened the time to development of SPMS and reduced or eliminated relapses.

Relapsing Multiple Sclerosis (RMS), first line.

Injection-site reactions.

Flu-like symptoms, muscle aches, asthenia, chills, and fever.

Ocrelizumab, cladribine, and diroximel fumarate.

Insidious neurologic progression for 1 year and 2 out of 3 criteria: evidence for dissemination in space in the brain or spinal cord, or positive cerebrospinal fluid.

The recognition of the importance of humoral immunity and B cells in MS.

Dihydroorotate dehydrogenase.

Serious herpes virus infections.

Flu-like symptoms, mild lab abnormalities, and injection-site reactions.

Nuclear factor (erythroid-derived 2)-like 2 pathway inhibitor.

A recently approved selective S1P receptor modulator effective in RMS.

Relapsing form of MS (RMS).

Evoked potentials to assess nerve conduction and retinal imaging by optical coherence tomography.

Injection-site inflammation, flu-like symptoms, rhinitis, and headache.

Approved but not yet commercially available.

Initiate therapy in patients with a first attack who are at high risk for MS or in patients diagnosed with Relapsing MS (RMS).

It is the active metabolite of leflunomide, an immune suppressant used in rheumatoid arthritis.

A possible low risk of increased malignancies, including breast cancer.

Immunomodulation through downregulating MHC expression, decreasing proinflammatory cytokines, and inhibiting T-cell proliferation.

By monthly subcutaneous injection at home.

Progressive multifocal leukoencephalopathy (PML).

Electric shock-like sensations evoked by neck flexion.

Less than 10%.

Prompt referral to a specialist.

32–36%.

Subcutaneous injection, 3 times weekly.

It is one of the distinctive pathologies contributing to the disease.

It can induce prolonged remission in many RMS patients but is not recommended for progressive MS.

Symptoms must last for more than 24 hours and occur as distinct episodes separated by at least 1 month.

Mononuclear cell pleocytosis and increased levels of intrathecally synthesized IgG.

Not fully known.

Intramuscular injection, once weekly.

Subcutaneous injection, every other day.

Extending the dosing interval from 4 to 6 weeks.

Mild abnormalities in liver function tests, heart block, and bradycardia.

Magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis.

They modify the course of MS through suppression or modulation of immune function.

Slowly progressive symptoms from onset.

Not fully known.