How Do Anti-Asthmatic Monoclonal Antibodies Work?

Anti-asthmatic monoclonal antibodies are medications that are used to treat severe asthma and other inflammatory conditions that do not adequately respond to standard anti-inflammatory treatments such as corticosteroids.

Anti-asthmatic monoclonal antibodies are laboratory-produced proteins cloned from a single type of white cell. Anti-asthmatic monoclonal antibodies block the activity of specific types of inflammatory proteins (cytokines) released by immune cells that are implicated in chronic pulmonary inflammatory diseases.

Most anti-asthmatic monoclonal antibodies work by blocking the activity of interleukin-5 (IL-5), a cytokine secreted by many types of cells. IL-5 is responsible for the maturation, release and survival of eosinophils, an immune cell that plays a prominent role in allergic airway diseases.

Interleukin-5 also stimulates the release of cytokines from basophils, another type of immune cells involved in airway inflammation. Interleukin-5 activates eosinophils and basophils by binding to protein molecules on their surfaces known as IL-5 receptors which respond to IL-5 and initiate inflammation.

Anti-asthmatic monoclonal antibodies bind to IL-5 receptors on eosinophils and basophils and prevent interleukin-5 from activating them. Anti-IL-5 monoclonal antibodies reduce inflammation in the following ways:

• Prevent IL-5 from promoting the proliferation of eosinophils.
• Induce programmed death (apoptosis) of eosinophils and basophils by attracting the immune system’s natural killer (NK) cells to them, in a process known as antibody-dependent cell-mediated cytotoxicity (ADCC).

Some anti-asthmatic monoclonal antibodies block the activity of immunoglobulin E (IgE), another type of antibody that the immune system produces in response to allergens. The anti-IgE monoclonal antibodies bind to IgE and prevent the stimulation of IgE receptors on mast cells and basophils, and the resultant release of cytokines.

A new anti-asthmatic monoclonal antibody that is in clinical trials, prevents inflammation by inhibiting thymic stromal lymphopoietin (TSLP). TSLP is a cytokine that triggers airway inflammation, and is produced by epithelial cells in the lining of the respiratory system.

Anti-asthmatic monoclonal antibodies are administered as intravenous or subcutaneous injections for the treatment of the following conditions:

FDA-approved:

• Add-on maintenance treatment for severe uncontrolled asthma with eosinophilic phenotype
• Moderate-to-severe asthma uncontrolled with inhaled corticosteroids
• Hypereosinophilic syndrome, an inflammatory condition with persistent eosinophilia
• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), a condition that causes severe asthma and blood vessel inflammation
• Add-on maintenance treatment for chronic rhinosinusitis (inflammation of nasal passage and sinuses) with nasal polyps that does not respond to nasal corticosteroids
• Chronic idiopathic urticaria (hives) that does not respond to antihistamine treatment
• Add-on maintenance treatment for nasal polyps that do not respond to nasal corticosteroids

Orphan designation:

• Eosinophilic esophagitis, a condition that inflames the esophagus

Side effects of anti-asthmatic monoclonal antibodies may include the following:

• Injection site reactions
• Headache
• Transient elevation in creatine phosphokinase (CPK)
• Nasopharyngitis (inflammation of nose and throat)
• Pharyngitis (throat inflammation)
• Oropharyngeal pain (mouth and throat pain)
• Sinusitis (inflammation of the sinuses)
• Allergic rhinitis (inflammation of the nasal passage)
• Bronchitis (inflammation of the bronchial passage)
• Viral and other upper respiratory tract infections
• Lower respiratory tract infection
• Dyspnea (shortness of breath)
• Cough
• Nasal congestion
• Nasal dryness
• Arthralgia (joint pain)
• Arthritis (joint inflammation)
• Generalized pain
• Back pain
• Leg pain
• Arm pain
• Musculoskeletal pain
• Fracture
• Muscle spasms
• Dizziness
• Fatigue
• Asthenia (weakness)
• Pyrexia (fever)
• Influenza
• Earache
• Ear infection
• Toothache
• Systemic nonallergic reactions
• Systemic allergic/hypersensitivity reactions such as:
  • Rash
  • Urticaria (hives)
  • Pruritus (itching)
  • Dermatitis
  • Eczema
• Anaphylaxis (severe allergic reaction)
• Lymphadenopathy (swelling of lymph nodes)
• Hair loss
• Nausea
• Upper abdominal pain
• Gastroenteritis
• Diarrhea
• Urinary tract infection
• Cystitis (inflammation of the bladder)
• Viral infection
• Severe thrombocytopenia (low platelet count in the blood)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of anti-asthmatic monoclonal antibody drugs include:

• cromolyn sodium
• benralizumab
• Cinqair
• Fasenra
• mepolizumab
• Nucala
• omalizumab
• reslizumab
• tezepelumab (pending FDA approval)
• Xolair