Biological Therapies in Multiple Sclerosis

Biologics for MS

Biologics for MS

Biological therapies, also known as biologics, have revolutionized the treatments of chronic inflammatory conditions such as MS (multiple sclerosis) which were previously thought incurable.

These therapies work by targeting specific immune cells or proteins in the body that are involved in the inflammatory process that damages the nervous system in MS.

Biologic Therapies for Multiple Sclerosis

Management of multiple sclerosis is a continuously advancing area in neuroscience where newer studies are being done to provide the best drug to control the disease progression and reduce morbidity and mortality.

Besides steroids, biological therapies are the mainstay of treatment for MS nowadays. Except for a few side effects, biological therapies are very targeted and associated with much fewer side effects compared to corticosteroids.

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Biologics for MS: Interferons:

Beta interferons are some of the commonest drugs used in multiple sclerosis. They are used to alleviate the frequency as well as the duration of acute relapses however they can cause flu-like illness and marrow suppression and have particular indications for which they can be used.

  1. Relapsing-remitting disease in which the patient can walk 100 meters unaided.
  2. Secondary progressive disease in which the patient can walk 10 meters unaided.

Some of the commonly used brands of interferons are:

  1. Interferon Beta 1A is available under the brands Avonex and Rebif
  2. Interferon Beta 1B is available under the brands Betaseron and Extavia
  3. PEG-Interferon Beta 1A is available under the brand name Plegridy.

 Dosage and administration:

Interferon beta therapies FDA approved for the treatment of relapsing-remitting multiple sclerosis

Drug Trade name Year of FDA approval Route of administration Dosing Frequency
Interferon beta-1b Betaseron, Extavia 1993 Subcutaneous 0.25 mg Every other day
Interferon beta-1a Avonex 1996 Intramuscular 30 μg Once weekly
Interferon beta-1a Rebif 2002 Subcutaneous 22 or 44 μg 3 times weekly
Peginterferon beta-1a Plegridy 2014 Subcutaneous 125 μg Once every 2 wk

Side Effects:

Its side effects range from mild flu-like illness to severe body aches and bone marrow depression to severe transaminitis.

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Biologics for MS: Glatiramer Acetate:

Trade name: Copaxone

The way that COPAXONE (Glatiramer Acetate) works is by acting as an immune decoy, which means that it misleads the antibodies in the body away from the myelin sheath.

By doing so, it helps to prevent damage to the myelin sheath, which can occur when the body’s immune system attacks it.

Medicine Active ingredient Average molecular weight Amino acids Immune action
COPAXONE Glatiramer acetate 5,000 – 9,000 daltons L-glutamic acid, L-alanine, L-tyrosine, and L-lysine Acts as an immune decoy, misleading antibodies away from the myelin sheath


Copaxone comes in two prefilled syringes of 20 mg and 40 mg per mL. 20mg dose is given subcutaneously each day or 40mg dose is given three times a week 48 hours apart. It is usually administered around the belly button, arms, and thighs.

Side Effects

Its side effects include site administration lipoatrophy, flu-like illness, headaches, nausea, and occasional diarrhea. Diplopia, chest tightness, opportunistic infections, vaginal candidiasis, and hepatitis can occur commonly.

Drug interactions are not studied in many trials for this drug.

Its use in pregnancy and lactation in humans is not studied yet however animal trials have shown no adverse effects.

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Biologics for MS: Cladribine:

Cladribine is a synthetic purine analog that belongs to the class of anti-metabolite and anti-pyrimidine agents.

The discovery of cladribine’s potential as a treatment for multiple sclerosis (MS) came about incidentally when scientists observed that adenosine deaminase (ADA) deficiency caused the destruction of B-cell lymphocytes by leading to the accumulation of deoxynucleotides in the cells [Ref].

This discovery lead to the hypothesis that Cladribine could be used as a selective immune reconstitution therapy (SIRT) for MS.

Compared to other maintenance therapies for MS that result in long-term immunosuppression, cladribine acts as a short-term immunosuppressant.

It underwent several stages of regulatory approval before Merck-Serono released data from the Cladribine Tablets Treating MS Orally (CLARITY) trial in 2008, which demonstrated the drug’s effectiveness and safety for treating MS.

The following table summarizes the regulatory approval timeline for cladribine:



1991 Cladribine receives FDA approval for treating hairy cell leukemia
2006 Merck-Serono submits an application for European approval of cladribine for treating MS
2010 European Medicines Agency approves cladribine for treating relapsing-remitting MS in the EU
2019 FDA approves cladribine for treating relapsing forms of MS in the US

Mechanism of action of Cladribine:

Cladribine selectively disrupts T-cell (cell-targeting) and B-cell (humoral) immunity by mimicking severe immunodeficiency disorder.

When present in high concentrations within cells, it increases the expression of deoxycytidine kinase (DCK), ultimately resulting in lymphocyte apoptosis.

How to administer Cladribine:

Cladribine is an orally administered drug used for the treatment of multiple sclerosis. The FDA-approved dosing regimen involves the administration of 3.5 mg/kg of cladribine over the course of two years, with two treatment courses separated by a twelve-month interval.

During the first treatment course, the drug is given over four to five consecutive days in the first month, followed by an equivalent dose over four to five consecutive days in the second month.

The second treatment course of cladribine follows the same frequency and dosing schedule as the first and is administered twelve months later.

The recommended dosing for an adult of average body weight is estimated to be approximately 10 to 20 mg daily for 4 to 5 days.

However, prescribers must follow the manufacturer’s specific guidelines for weight-based dosing in accordance with the approved federal guidelines of the Risk Evaluation and Mitigation Strategies (REMS) program.

To ensure the safe remission of the disease without severe lymphopenia or other adverse events, patients receiving cladribine therapy must be monitored regularly. The table below summarizes the recommended monitoring schedule:

Monitoring Parameter Frequency
Lymphocyte count Baseline, every 3 months for 18 months after each treatment course, then annually
Complete blood count Baseline, every 3 months for 18 months after each treatment course, then annually
Serum creatinine Baseline, every 6 months for 18 months after each treatment course, then annually
Liver function tests Baseline, every 6 months for 18 months after each treatment course, then annually
Urinalysis Baseline, every 6 months for 18 months after each treatment course, then annually

Side effects of Cladribine:

  • Lymphopenia
  • Headaches
  • Herpetic infections
  • Nasopharyngitis
  • Alopecia
  • Increased risk of malignancy.

Contraindications to Cladribine use:

  • Hepatic cirrhosis
  • CKD (chronic kidney disease)
  • Active HIV
  • Active Tuberculosis
  • Concomitant use of immunosuppresants like Cyclophosphamide, Azathioprine
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Biologics for MS: Fingolimod:

Fingolimod is a medication that modulates sphingosine 1-phosphate receptors and is indicated for the treatment of relapsing-remitting multiple sclerosis (MS).

It has also been studied for its potential to manage lung complications associated with COVID-19.

Mechanism of action:

Fingolimod is a medicine that is used to treat a type of multiple sclerosis called relapsing-remitting MS.

It works by binding to certain receptors in the body and preventing lymphocytes from leaving the lymph nodes.

This reduces the inflammation that causes MS symptoms. The exact way that fingolimod works is not completely understood, but it may also prevent lymphocytes from entering the central nervous system.


Fingolimod is slowly absorbed with a bioavailability of about 93%. It reaches its steady state concentration within 1 to 2 months.

Route of administration and elimination:

It is taken orally. Most of the drug is excreted via the kidneys as inactive metabolites. Only about 2.5% gets excreted in the feces.

Adverse effects:

  • Hypotension
  • Tachycardia
  • Nausea
  • Diarrhea
  • Indigestion
  • Cardiomyopathies

Drug interaction: 

Fingolimod can interact with other immunosuppressants leading to disturbance in half-life.

It is present in 0.25 mg or 0.5 mg pills.

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Biologics for MS: Natalizumab:

Natalizumab is a monoclonal antibody that specifically targets alpha 4 integrin subunits, thereby inhibiting immune cell migration. It is indicated for the treatment of Crohn’s disease and multiple sclerosis.

Brand name: Tysabri

Mechanism of action:

This drug attaches to the α4 subunit of α4b1 and α4b7 integrins found on the surface of all leukocytes except neutrophils. It inhibits the adhesion of leukocytes to their counter-receptors that is mediated by α4.

Route of administration: Intravenous

Dosage: 150mg/15mL, 300 mg/15 mL

Adverse effects:

  • Opportunistic infections
  • Transaminitis
  • Progressive multifocal leukoencephalopathy
  • Headache
  • Dizziness
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Biologics for MS: Alemtuzumab:



Drug Name Alemtuzumab (Lemtrada)
Type of Drug Monoclonal Antibody
Mechanism of Action Targets CD52, a protein found on the surface of immune cells. Causes depletion of T and B lymphocytes, leading to reduced inflammation and damage to nerve cells.
FDA Approval Year 2014
Indication Treatment of relapsing-remitting multiple sclerosis (RRMS)
Dosage Forms Solution for intravenous infusion
Dosage Strengths 12 mg per vial
Dosing Regimen Two annual treatment courses consisting of daily IV infusions for 5 consecutive days at a dose of 12 mg/day followed by another 3 consecutive days of treatment 12 months later
Common Side Effects Rash, headache, fever, nausea, urinary tract infection, fatigue
Serious Side Effects Autoimmune disorders (thyroid disease, idiopathic thrombocytopenic purpura), infusion reactions, infections, bleeding disorders
Monitoring Blood cell counts, liver function tests, thyroid function tests, kidney function tests, and pregnancy testing for women of childbearing potential
Contraindications Active infections, history of cancer or severe immune system disorders, HIV, active systemic infections, pregnancy, and breastfeeding
Drug Interactions No significant drug interactions have been reported
Cost Approximately $100,000 USD per treatment course


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Biologics for MS: Ocrelizumab:



Trade Name Ocrevus
Generic Name Ocrelizumab
Drug Class Monoclonal Antibody
Indications Treatment of Relapsing-Remitting MS and Primary Progressive MS
Administration Route Intravenous Infusion
Dosage Form Solution for infusion
Dosage The initial infusion of 300 mg followed by 600 mg after 2 weeks. Subsequent infusions of 600 mg every 6 months
Mechanism of Action Targets CD20-positive B cells, leading to depletion of B cells
Manufacturer Genentech/Roche
FDA Approval March 2017
Common Side Effects Infusion reactions, upper respiratory tract infections, and herpes infections.
Contraindications Hypersensitivity reactions to Ocrelizumab, active hepatitis B virus infection, and active hepatitis C virus infection


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Biologics for MS: Ofatumumab:


Ofatumumab (Kesimpta)

Drug class Monoclonal antibody (CD20 inhibitor)
Mechanism of action Depletes B-cells
Administration Subcutaneous injection
Dosage and frequency First dose: 20 mg subcutaneously, followed by a second dose of 20 mg after 1 week. Subsequent doses of 20 mg are given every 4 weeks.
Approved for Relapsing forms of multiple sclerosis
Common side effects Injection-related reactions, upper respiratory infections, headache, and fatigue
Pregnancy category Category C
Contraindications Active hepatitis B infection, severe immunodeficiency syndrome, and hypersensitivity to Ofatumumab


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Biologics for MS: Dimethyl fumarate (Tecfidera):



Drug Name Dimethyl fumarate
Brand Name(s) Tecfidera, Bafiertam (oral formulations)
Mechanism of Action Activates the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, which regulates antioxidant and anti-inflammatory responses; may also modulate immune cell function
FDA Approval March 2013 for relapsing forms of MS
Dosing Starting dose of 120 mg twice daily, increased to a maintenance dose of 240 mg twice daily after 7 days; may be taken with or without food
Common Side Effects Flushing, gastrointestinal symptoms, lymphopenia, elevated liver enzymes
Pregnancy Category C
Monitoring Regular blood tests to monitor lymphocyte and liver function
Contraindications History of severe allergic reaction to dimethyl fumarate or any component of the formulation, or to monomethyl fumarate; severe renal impairment
Drug Interactions None of the clinically significant drug interactions known


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Biologics for MS: Teriflunomide (Aubagio):

Drug Name


Brand Name Aubagio
Drug Class Immune modulator
FDA Approval September 2012
Indication Relapsing forms of multiple sclerosis
Dosage 7 mg or 14 mg orally once daily
Mechanism of Action Selectively and reversibly inhibits dihydroorotate dehydrogenase, blocking de novo pyrimidine synthesis, which is crucial for activated lymphocytes
Common Side Effects Hair loss, diarrhea, nausea, abdominal pain, abnormal liver function tests
Contraindications Pregnancy, severe hepatic impairment
Drug Interactions Warfarin, leflunomide, cholestyramine
Monitoring CBC, liver function tests, blood pressure
Pregnancy Category X (contraindicated in pregnancy)


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Biologics for MS: Siponimod:


Information about Siponimod in MS

Indication Treatment of multiple sclerosis (MS)
Mechanism of action Siponimod is a selective modulator of sphingosine-1-phosphate (S1P) receptor subtypes 1 and 5.

By binding to these receptors, it reduces the number of lymphocytes in the blood and prevents their migration into the central nervous system, which helps to reduce inflammation and prevent MS relapses.

Clinical trials In phase III clinical trial, Siponimod was found to reduce the risk of disability progression and the number of relapses in patients with secondary progressive MS compared to placebo.
Dosage The recommended starting dose is 0.25 mg once daily, which can be increased to 2 mg once daily after a titration period.
Administration Siponimod is taken orally, with or without food.
Adverse effects Common adverse effects include headaches, high blood pressure, and increased liver enzymes. More serious adverse effects can include infections, macular edema, and cardiovascular events.
Contraindications Siponimod is contraindicated in patients with severe liver impairment and those taking certain medications that affect heart rate or rhythm.
Pregnancy and breastfeeding Siponimod should not be used during pregnancy or breastfeeding due to potential risks to the fetus or infant.
Monitoring Patients taking Siponimod should have regular liver function tests and blood pressure monitoring. Eye exams are also recommended to monitor for macular edema.


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Summary of Biologics for MS:


Brand Name

Mechanism of Action

Natalizumab Tysabri Binds to α4-subunit of α4b1 and α4b7 integrins, preventing migration of immune cells
Alemtuzumab Lemtrada Targets CD52 antigen on lymphocytes, leading to depletion of lymphocytes
Ocrelizumab Ocrevus Targets CD20 antigen on B-lymphocytes, leading to depletion of B-cells
Rituximab Rituxan Targets CD20 antigen on B-lymphocytes, leading to depletion of B-cells
Ofatumumab Kesimpta Targets CD20 antigen on B-lymphocytes, leading to depletion of B-cells
Interferon beta Avonex, Betaseron, Rebif Stimulates the immune system to fight against viral infections and cancer
Glatiramer acetate Copaxone Mimics myelin basic protein, reducing autoimmune response against myelin
Fingolimod Gilenya Modulates sphingosine 1-phosphate receptors to reduce lymphocyte circulation
Dimethyl fumarate Tecfidera Activates nuclear factor (erythroid-derived 2)-like 2 (Nrf2), leading to anti-inflammatory effects
Teriflunomide Aubagio Inhibits dihydroorotate dehydrogenase, reducing the proliferation of T- and B-lymphocytes
Siponimod Mayzent Modulates sphingosine 1-phosphate receptors to reduce lymphocyte circulation
Cladribine Mavenclad Disrupts T-cell and B-cell immunity by inducing lymphocyte apoptosis


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Written by Dr. Ahmed

I am Dr. Ahmed (MBBS; FCPS Medicine), an Internist and a practicing physician. I am in the medical field for over fifteen years working in one of the busiest hospitals and writing medical posts for over 5 years.

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