Is Fasenra (benralizumab) an immunosuppressant?

Is Fasenra (Benralizumab) an Immunosuppressant?

Fasenra (benralizumab) is not a traditional immunosuppressant but rather a targeted biologic that depletes eosinophils through antibody-dependent cell-mediated cytotoxicity (ADCC), without broadly suppressing the immune system like corticosteroids or conventional immunosuppressive agents. 1

Mechanism of Action

Benralizumab functions through a highly specific mechanism that distinguishes it from conventional immunosuppressants:

• It is a humanized afucosylated monoclonal antibody that binds directly to the IL-5 receptor alpha (IL-5Rα) on eosinophils and basophils 1
• The absence of fucose in the Fc domain facilitates binding to FcɣRIII receptors on natural killer (NK) cells, leading to rapid apoptosis of eosinophils through ADCC 1
• This results in near-complete depletion of eosinophils within 24 hours of dosing, with median blood eosinophil counts reduced to 0 cells/μL 1, 2

This targeted mechanism differs fundamentally from traditional immunosuppressants that broadly suppress multiple immune pathways. For comparison, corticosteroids suppress cell-mediated immunity by inhibiting interleukin production across the board, while TNF-α inhibitors and other biologics mentioned in immunosuppression guidelines act on different inflammatory pathways 3.

Clinical Classification

Benralizumab is classified as a biologic disease-modifying anti-rheumatic drug (bDMARD) and specifically as an anti-IL-5 receptor therapy, not as a conventional immunosuppressant 3:

• Guidelines on immunotherapy-related toxicities list benralizumab separately from traditional immunosuppressants like mycophenolate, calcineurin inhibitors, and cyclophosphamide 3
• It is grouped with other targeted cytokine inhibitors (anti-IL-4Rα, anti-IL-6R) rather than broad immunosuppressive agents 3

FDA-Approved Indications

Benralizumab is approved for:

• Add-on maintenance treatment of severe asthma with an eosinophilic phenotype in patients aged 6 years and older 1
• Treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA) 1

The American College of Rheumatology recommends benralizumab specifically for EGPA patients with refractory asthma/ENT disease without systemic manifestations, at 30 mg subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks 4.

Safety Profile and Long-Term Eosinophil Depletion

Importantly, near-complete eosinophil depletion with benralizumab does not increase long-term safety risks or infection rates comparable to traditional immunosuppressants 5, 6:

• In real-world studies with up to 48 months of follow-up, only 21.1% of patients experienced adverse events, with just 1.6% related to treatment 5
• The most common adverse events were nasopharyngitis (18-21%), worsening asthma (11-15%), and injection site reactions—not the opportunistic infections seen with broad immunosuppression 1, 2
• Over 5 years of treatment, adverse event rates remained stable (28.5-32.4 per 100 patient-years) and did not increase with prolonged exposure 6

This contrasts sharply with traditional immunosuppressants like TNF-α inhibitors, which carry significant risks of tuberculosis reactivation, hepatitis B reactivation, and opportunistic infections requiring extensive pre-treatment screening 3.

Key Clinical Distinctions

Unlike conventional immunosuppressants, benralizumab does not require:

• Tuberculin skin testing or chest radiographs prior to therapy 3
• Hepatitis serology screening (though prudent in any patient receiving biologics) 3
• Avoidance of live vaccines (not specifically contraindicated in FDA labeling) 1
• Prophylaxis against opportunistic infections 3

The European Respiratory Society does recommend therapeutic drug monitoring when using benralizumab, suggesting some level of immune modulation warrants attention 7, 4.

Clinical Implications

For practical purposes, benralizumab should be considered a targeted eosinophil-depleting biologic rather than an immunosuppressant when:

• Counseling patients about infection risk (significantly lower than traditional immunosuppression)
• Planning surgical procedures (no need for stress-dose steroids)
• Evaluating for drug interactions with other immunomodulators
• Assessing candidacy in patients with contraindications to broad immunosuppression

The mechanism of action—selective eosinophil depletion via ADCC—preserves other immune functions, explaining why benralizumab maintains efficacy without the broad immunosuppressive toxicity profile seen with corticosteroids, calcineurin inhibitors, or cytotoxic agents 1, 5.