Biologics & ABPA - what are they and what can they do?

Biologic medications (also known as biologics) are a class of drugs derived from living organisms or their cells. These treatments are used for various conditions, especially those involving the immune system, such as autoimmune diseases, cancers, and chronic inflammatory disorders. Here’s a breakdown of biologics:

1. What Are Biologics?

• Biologics are large, complex molecules made using biotechnology. They can be derived from living organisms such as bacteria, yeast, or animal cells.
• Unlike traditional medications (chemically synthesized), biologics are produced through genetic engineering or cell culture techniques.

2. Types of Biologic Drugs:

• Monoclonal Antibodies (mAbs): These are engineered antibodies designed to target specific proteins or cells, such as tumor cells or immune system components. Examples include drugs like adalimumab (Humira) for rheumatoid arthritis and rituximab (Rituxan) for certain cancers.
• Interferons: Proteins that modify immune system activity. They are used for conditions like multiple sclerosis and hepatitis C.
• Vaccines: Biologic drugs used to stimulate the immune system to protect against infectious diseases (e.g., the flu vaccine, COVID-19 vaccines).
• Cell and Gene Therapies: These involve altering genes or using stem cells to treat genetic disorders or cancers. CAR T-cell therapies are an example for cancer treatment.

3. Conditions Treated by Biologics:

• Autoimmune Disorders: Such as rheumatoid arthritis, Crohn’s disease, and psoriasis.
• Cancer: Biologics like monoclonal antibodies and immune checkpoint inhibitors target cancer cells.
• Infections: Some biologics, including vaccines, protect against infections like hepatitis, flu, and COVID-19.
• Chronic Inflammatory Conditions: Such as asthma and inflammatory bowel disease (IBD).

4. Advantages of Biologics:

• Targeted Action: Biologics can target specific parts of the immune system or cells involved in disease, leading to more effective treatments with fewer side effects compared to traditional drugs.
• Personalized Treatments: Some biologics can be customized based on a patient’s genetics, improving outcomes for certain conditions.

5. Limitations and Side Effects:

• Expensive: Biologics tend to be more expensive than traditional medications due to the complex production process.
• Injection or Infusion: Many biologics are administered through injections or intravenous infusions rather than oral tablets.
• Immune System Effects: Since biologics modify immune system function, they can increase the risk of infections and other immune-related side effects.

Examples of Biologic Medications:

• Humira (adalimumab) for autoimmune diseases.
• Keytruda (pembrolizumab) for cancer treatment.
• Enbrel (etanercept) for rheumatoid arthritis.

Biologics are reshaping the treatment landscape, particularly in conditions where traditional medications were less effective.

In the case of Allergic Bronchopulmonary Aspergillosis (ABPA), biologic medications are increasingly being explored and used as part of treatment, particularly for patients with more severe or resistant forms of the disease. ABPA is an allergic reaction to the fungus Aspergillus, which can lead to airway inflammation and lung damage. Biologic medications, often aimed at modulating the immune system, help in managing this complex condition, especially when conventional treatments like corticosteroids fail to control symptoms or lead to significant side effects.

How Biologics Help in ABPA Treatment:

1. Targeting Immune System Pathways:
   • Biologics used in ABPA primarily work by targeting specific immune system pathways that drive the inflammatory response triggered by the Aspergillus fungus.
   • For example, biologics that target interleukin-5 (IL-5), such as mepolizumab (Nucala), can help reduce eosinophil levels, a type of white blood cell involved in allergic reactions and inflammation in ABPA. Dupixent, another biologic, targets IL-4 and IL-13, which are cytokines involved in the inflammatory cascade in ABPA, potentially improving lung function and reducing exacerbations .
   • Omalizumab (Xolair) acts directly on the patients IgE antibodies, preventing them triggering allergic inflammation
2. Reducing Steroids – For ABPA patients who require long-term corticosteroid use, biologics may offer an alternative, reducing dependence on steroids and lowering the risk of long-term steroid side effects (e.g., osteoporosis, diabetes, and weight gain).
   • Biologics can provide a more targeted approach, addressing the underlying immune mechanism, rather than just suppressing the overall immune response with steroids .
3. Clinical Evidence:
   • In trials, biologics like mepolizumab have shown improvements in asthma control and reduced exacerbations, suggesting potential benefits for ABPA patients with significant asthma components.
   • Dupilumab has also demonstrated potential benefits in patients with ABPA and associated asthma, showing improvements in lung function and reduction in eosinophil levels, thus addressing both the underlying inflammation and allergic reactions .
4. Safety and Efficacy:
   • While biologics are typically used in cases where standard treatments (steroids, antifungals) are not sufficient or appropriate. These medications are generally well-tolerated, but they do carry risks, such as increased susceptibility to infections due to immune system modulation** .

Summary:

Biologic therapies represent an option for patients with ABPA, particularly those with severe symptoms or who struggle with long-term steroid use. By targeting specific immune pathways, biologics help reduce inflammation and improve lung function without the broad immunosuppression of steroids. Drugs like mepolizumab and dupilumab are showing encouraging results, though their use in ABPA is still being refined and evaluated in clinical trials.

If you’re exploring biologics for ABPA treatment, consulting with a specialist in pulmonary or immunologic disorders is crucial, as the benefits and risks of these drugs need to be carefully balanced for each individual patient.

**One common concern is whether these treatments could increase susceptibility to viral infections, particularly respiratory viruses.

Immune Modulation and Viral Infections: Omalizumab (Anti-IgE): Omalizumab reduces IgE levels, which are primarily involved in allergic reactions, not antiviral immunity. Studies show that it may actually decrease the frequency of respiratory viral infections by reducing inflammation and preventing exacerbations triggered by viruses. In clinical trials, omalizumab was not associated with increased viral infection rates and has been shown to lower asthma exacerbations caused by viral infections.

Mepolizumab and Benralizumab (Anti-IL-5): These biologics target IL-5, which reduces eosinophil counts. Eosinophils play a minor role in viral defense, but their reduction does not seem to impair the body’s ability to fight viruses significantly. Data suggest that mepolizumab and benralizumab do not increase the incidence of viral infections and can reduce asthma exacerbations, including those triggered by viruses.

Dupilumab (Anti-IL-4/IL-13): Dupilumab inhibits IL-4 and IL-13 signaling, key cytokines in allergic inflammation. It is not associated with increased viral infection susceptibility in clinical trials. It may enhance antiviral defenses by reducing Th2-skewed inflammation, potentially allowing the body to mount a better response to viruses.

Evidence from Studies: Studies have consistently shown that biologics can reduce asthma exacerbations, many of which are triggered by viral infections, suggesting they do not compromise the immune system’s ability to fight viruses. No significant increase in viral infections has been observed in large clinical trials for these medications, and they are generally considered safe in this context.

Conclusion: Biologic medications for asthma do not appear to increase vulnerability to viral infections. In fact, they may reduce the risk of virus-induced asthma exacerbations by controlling airway inflammation. However, patients with severe asthma or comorbid conditions should always consult their healthcare provider regarding potential risks.