What to do When Biologics Don’t Work

As part of a collection of presentations on difficult cases, Marco Caminati, MD, of Verona University Hospital in Italy, and Alvaro Cruz, MD, of the Federal University of Bahia in Salvador, Brazil, presented case studies on what to do when biologics are not effective. This was part of a presentation given at the 2018 AAAAI Annual Meeting.

Open-Ended Case Discussions

Dr. Caminati first discussed a 41-year-old white non-smoking woman with late-onset asthma after her second pregnancy, whose condition worsened over the course of two years. Her asthma remained difficult to treat despite fluticasone and salmeterol treatment, followed by beclomethasone/formoterol treatment plus montelukast treatment. The patient needed an oral corticosteroid (OCS) almost monthly, had poor exercise performance, and had a fully positive reversibility test. Differential diagnoses were ruled out. Other clinical findings included blood hyper-eosinophilia, bronchial hyper-secretion, relapsing chronic rhinosinusitis, upper-lobes bronchiectasis, and dependence on OCS. With that information, the team treated her with itraconazole. After two months, the patient stopped OCS and her spirometry normalized. “But that is not a long-term treatment, so what about the future?” Dr. Caminati wondered as he closed his first case discussion.

The second case involved a 20-year-old white male with childhood asthma. His asthma had been difficult to treat for two years, despite fluticasone and salmeterol treatment, followed by budesonide/formeterol, and montelukast. The patient required OCS almost monthly, as well as a beta2-adrenergic agonist weekly. He, too, had poor exercise performance. Treatment with mepolizumab began, and lung function dropped. Dr. Caminati used the case to open a discussion on whether combining mepolizumab and omalizumab is appropriate and sustainable. “Do we need to target more than one mechanism and perhaps combine two biologics?” he asked.

Treatment-Resistant Severe Asthma—What is it and What to do?

Dr. Cruz then took the podium to discuss definitions of and options for treatment-resistant severe asthma.

He presented the World Health Organization’s (WHO) definition of severe asthma as “uncontrolled asthma, which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity (including impaired lung function or reduced lung growth in children).” According to the WHO definition, Dr. Cruz offered three groups of severe asthma: untreated severe asthma, difficult-to-treat asthma, and treatment-resistant severe asthma.

The definition of severe asthma according to the American Thoracic Society and European Respiratory Society is “asthma [that] requires treatment with guideline-suggested medications for Global Initiative for Asthma steps 4-5 asthma (high-dose inhaled corticosteroid and long-acting beta-adrenoceptor agonist or leukotriene modifier/theophylline) for the previous year or systemic corticosteroid for >50% of the previous year to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy.”

Dr. Cruz offered the audience an ABCDE checklist to help practitioners examine reasons a patient’s asthma might be uncontrolled:

  • Adhesion/adherence (regular use of controllers and proper use of inhalers)
  • Bronchial disease other than asthma
  • Comorbidities
  • Different diagnosis
  • Exposure to allergens and/or irritants

In addition, he walked the audience an algorithm for the selection of a biologic for severe asthma, which appeared in a 2017 article by Bousquet et al in the European Respiratory Journal.

Finally, Dr. Cruz discussed alternatives for patients who are not eligible for treatment or when treatment does not work. In such cases, he urged practitioners to consider management in reference clinics (guided by biomarkers); provide optimal management of comorbidities; use shared decision-making, provide education, and develop an action plan; allow patients guided self-management; help patients with adherence; and encourage patients to lose weight, engage in physical activity, practice breathing exercises, quit smoking, and control environmental factors. He also mentioned maintenance and reliever therapy, azithromycin and SLIT in certain cases, and bronchial thermoplasty.

Presentation 1001: Difficult Cases: Part I