GAtherton

Thinking about joining a clinical trial? What are your concerns?

by GAtherton

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.

by GAtherton

Olorofim - a promising new antifungal candidate for aspergillosis treatment.

Olorofim represents a significant advancement in treating aspergillosis, particularly for patients who cannot tolerate or do not respond to existing antifungal therapies. Here’s why it’s important:

1. Novel Mechanism of Action

• Olorofim is the first antifungal in a new class called orotomides. It inhibits dihydroorotate dehydrogenase, an enzyme essential for fungal pyrimidine biosynthesis.
• This mechanism is entirely distinct from existing antifungal classes (azoles, polyenes, and echinocandins), making it effective against strains resistant to current treatments​

2. Broad Spectrum and Potency

• It has demonstrated activity against azole-resistant Aspergillus species and other difficult-to-treat moulds, addressing a major gap in antifungal therapy​
• This includes rare and often lethal fungal infections like Scedosporium, Lomentospora, and Fusarium, as well as chronic conditions like Chronic Pulmonary Aspergillosis (CPA) and invasive aspergillosis.

3. Oral Administration

• Unlike many current treatments that require intravenous administration (e.g., amphotericin B), olorofim is taken orally, improving convenience and accessibility for patients needing long-term therapy.

4. Targeting Unmet Needs

• Aspergillosis, particularly invasive aspergillosis, has high morbidity and mortality rates, especially in immunocompromised patients (e.g., those with cancer, transplant recipients).
• Current treatments face challenges like resistance, toxicity, and drug-drug interactions. Olorofim addresses these limitations by offering a safer and more tolerable alternative​

5. Regulatory Recognition

• The drug has been granted Breakthrough Therapy Designation and Orphan Drug Status by the FDA and EMA, underscoring its potential to meet urgent medical needs​
  pharmaphorum GlobeNewswire

Future Implications

Olorofim's availability for treating Chronic Pulmonary Aspergillosis (CPA) depends on its successful progression through clinical trials and regulatory approval. Here's a summary of its current status and potential timeline:

1. Current Status:
   • Olorofim is in Phase 3 clinical trials (OASIS trial) for invasive fungal diseases, including invasive aspergillosis, a related but more acute condition than CPA.
   • Although the drug has shown promising results in earlier studies, the FDA recently issued a Complete Response Letter, indicating that additional clinical data is required before it can be approved in the U.S.​​
   • CPA is not explicitly listed as a primary indication in current trials, but success in related aspergillosis treatments could lead to future trials or off-label use for CPA.
2. Timeline to Approval:
   • If the ongoing Phase 3 trial and additional studies satisfy regulatory agencies, olorofim could receive an approval within 2–3 years for its initial indications (e.g., invasive aspergillosis).
   • For CPA specifically:
     • Additional trials may be needed to confirm efficacy and safety, potentially extending approval timelines by 3–5 years.
     • Off-label use might occur sooner, depending on clinician judgment and availability in regions with less restrictive policies.

Given the high unmet need in CPA and the novelty of olorofim’s mechanism, it is closely watched by both the medical community and regulators. If you're a patient with CPA, keeping in touch with your healthcare provider about ongoing trials and compassionate use programs may help you access new treatments sooner.

by GAtherton

UK National RSV vaccination program launched

by GAtherton

CPA patients have impaired neutrophil response to infection

by GAtherton

English prescription charge to rise 1st May 2024

by GAtherton

Chronic illness diagnosis and guilt

Living with a chronic disease can often lead to feelings of guilt, but it's important to recognize that these feelings are common and perfectly normal. Here are some reasons why individuals with chronic illnesses may experience guilt:

1. Burden on others: People with chronic illnesses may feel guilty about the impact their condition has on their loved ones, such as needing assistance with daily tasks, financial strain, or emotional stress. They may feel like they're a burden on their family and friends, which can lead to feelings of guilt and self-blame.
2. Inability to fulfill roles: Chronic illnesses can affect a person's ability to fulfil their roles and responsibilities, whether it's at work, in relationships, or within their family. They may feel guilty for not being able to meet expectations or for having to rely on others for support.
3. Perceived lack of productivity: Chronic illnesses can limit a person's ability to engage in activities they once enjoyed or pursue their goals and aspirations. They may feel guilty for not being as productive or accomplished as they were before their diagnosis.
4. Self-blame: Some individuals may blame themselves for their illness, whether it's due to lifestyle factors, genetics, or other reasons. They may feel guilty for not taking better care of themselves or for somehow causing their condition.
5. Comparison with others: Seeing others who appear healthy and able-bodied may trigger feelings of guilt or inadequacy in individuals with chronic illnesses. They may compare themselves to others and feel guilty for not being able to live up to societal expectations or norms.

Dealing with feelings of guilt associated with chronic illness can be challenging, but it's important to address them in a healthy and constructive way. Here are some strategies for coping with guilt:

1. Practice self-compassion: Be kind to yourself and recognize that having a chronic illness is not your fault. Treat yourself with the same compassion and understanding that you would offer to a loved one in a similar situation. You have an awful lot to come to terms with and it may take some time, give yourself that time and space.
2. Seek support: Talk to trusted friends or people who understand because they have been through the same experience eg in one of the support groups at the National Aspergillosis Centre, family members, or a therapist about your feelings of guilt. Sharing your emotions with others who understand can help validate your experiences and provide comfort and reassurance.
3. Set realistic expectations: Adjust your expectations and goals to align with your current abilities and limitations. Focus on what you can do rather than dwelling on what you can't, and celebrate your accomplishments no matter how small. In other words to use a phrase uttered regularly in the NAC support groups - find your new normal.
4. Practice gratitude: Cultivate a sense of gratitude for the support and resources available to you, as well as the things that bring you joy and fulfilment despite your illness. Focus on the positive aspects of your life rather than dwelling on feelings of guilt or inadequacy.
5. Engage in self-care: Prioritize self-care activities that promote your physical, emotional, and mental well-being, such as getting enough rest, eating a balanced diet, exercising within your limits, and engaging in activities that bring you pleasure and relaxation.
6. Challenge negative thoughts: Challenge negative thoughts and beliefs that contribute to feelings of guilt or self-blame. Replace them with more balanced and compassionate perspectives, reminding yourself that you are doing the best you can under challenging circumstances.

Remember that it's okay to seek professional help if you're struggling to cope with feelings of guilt or if they're significantly impacting your quality of life. A therapist or counsellor can provide additional support and guidance tailored to your specific needs and circumstances.

NOTE You may find it useful to also read our article on grief.

Graham Atherton, National Aspergillosis Centre April 2024

by GAtherton

ABPA guidelines update 2024

Authoritative health-based organisations throughout the world occasionally release guidelines for doctors on specific health problems. This helps everyone give patients a consistent level of the right care, diagnosis and treatment and is particularly useful when the health problem is relatively uncommon and access to expert opinion is difficult.

The International Society for Human and Animal Mycology (ISHAM) is one such international organisation that specialises in fungal diseases. It runs a lot of 'working groups' designed to address and discuss a whole range of fungal infections, run by ISHAM members from a wide range of backgrounds.

One such group is the ABPA working group, and this group has just released an update to its clinical practice guidelines for ABPA.

The new guidelines introduce a range of changes designed to efficiently capture more cases of ABPA, enabling the patient to get the right treatment. For example they suggest reducing the requirement for a total IgE test result score of 1000IU/mL to 500. They also suggest that all new admissions who are adults with severe asthma are routinely tested for total IgE, and children who symptoms are difficult to treat should also be tested. ABPA should be diagnosed when there is radiological evidence or appropriate predisposing conditions eg asthma, bronchiectasis along with IgE >500/IgG/eosinophils.

Doctors should take care not to miss cases of fungal sensitisation caused by fungi other than Aspergillus (ABPM).

Instead of staging ABPA, they suggest putting the patient into groups that don't suggest progression of the disease.

The group suggests not routinely treating ABPA patients who have no symptoms, and if they develop acute ABPA oral steroids or itraconazole. If the symptoms keep recurring then use a combination of prednisolone and itraconazole.

Biologic medication is not appropriate as a first option for treating ABPA

Read the full guidelines here

by GAtherton

Salbutamol nebuliser solution shortage

We have been informed that there is an ongoing shortage of salbutamol solutions for nebulisers that is likely to last until summer 2024. If you live in Greater Manchester and you have COPD or asthma your GP has been provided with guidelines to ensure that any impact on your care is minimised, and your GP will be able to advise you further.

GPs elsewhere in the UK will also need to prepare, and update your action plan accordingly.

If at all concerned contact your GP for advice, as all should be aware of this situation.

by GAtherton

Interactive tool for asthma patients to help self-assessment

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Asthma is a complex disease with many different causes & triggers. Sometimes asthma symptoms gradually get worse despite all efforts to control them, and one way that happens is when someone becomes allergic to Aspergillus. Allergic BronchoPulmonary Aspergillosis (ABPA) and Severe asthma with fungal sensitisation (SAFS) are two possible outcomes. This progression usually happens slowly and gradually so it is difficult to tell when the allergy began. This tool can help you assess if you need more help from your doctors, and what help may be available.

Asthma + Lung UK has developed an interactive tool to enable people with poorly controlled asthma to self-assess their likelihood of having severe asthma and ask for the support they need. This can be a useful way to find out if you could benefit from biologics (or other therapy).

Access self-assessment tool

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by GAtherton