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Biological drugs & ABPA

October 09 2020

Current mainstays of ABPA treatment include antifungals, anti-inflammatories (e.g. steroids) and asthma drugs. However, many of these cause serious side effects and not all patients respond to them sufficiently. Newer biological drugs (based on monoclonal antibodies, or ‘mAbs’) that target specific parts of the molecular machinery of inflammation have achieved good results for patients with severe asthma, and there is increasing evidence that they could also be useful for treating ABPA/SAFS in asthma and cystic fibrosis patients.
 
Omalizumab (brand name Xolair) is a mAb that neutralises free IgE directly and is approved in the UK as an add-on treatment for moderate/severe persistent asthma. It is an injection under the skin given every 2-4 weeks. It is prescribed by NHS asthma specialists but is normally only offered to patients who have had 4 courses of corticosteroids in the past year, or who are on continuous steroids.
Recently, scientists retrieved data from the Australian Xolair Registry (Wark et al., 2020) and found that Xolair significantly improved symptoms and reduced the number of exacerbations in 11 ABPA patients. Older case reports are summarised nicely by Li et al. (2017).
Mepoluzimab (brand name Nucala) is another mAb that targets the cytokine IL-5, which is one of the inducers of the eosinophilic response. It is approved in the UK for treating patients with severe eosinophilic asthma who aren’t responding to other treatments, but can only be used under expert supervision. As ABPA is also an eosinophilic disorder, a team in the US searched the scientific literature for cases where mepoluzimab had been used. All 8 cases showed improvement within 6 months and had an average improvment in FEV1 of 375 ml, with 4 cases also showing a substantial decrease in IgE levels (Tolebeyan et al., 2020).
 
Dupilumab (brand name Dupixent, targets IL-4/IL-13) was rejected by NICE earlier this year for use within the NHS on the grounds of cost and insufficient evidence (read more about this decision at PharmaPhorum). One recent case report describes a patient with ABPA and severe asthma whose condition was deteriorating despite taking daily oral and inhaled corticosteroids, who had previously not shown a strong response to treatment with itraconazole, benralizumab (anti-IL-5 mAb) or omalizumab. After 4 months of treatment with , her symptoms had almost completely resolved and she no longer took oral steroids (Mümmler et al., 2020). The authors emphasise that a history of failing treatment with some biologicals should not rule out trying others.
  • Read more about biological therapies at Asthma UK 
  • Read detailed information about ABPA diagnosis, subtypes, staging and treatments: Patel et al., 2019