Long-term responsiveness to mepolizumab after failure of omalizumab and bronchial thermoplasty: Two triple-switch case reports

Abstract

Severe asthma affects between 5 and 10% of patients with asthma worldwide and requires best standard therapies at maximal doses. A subgroup of patients remains refractory to all treatments. We describe two case reports with severe allergic asthma who progressively worsened over the years despite the best therapy. The patients were first treated with omalizumab, which was completely ineffective, and then with bronchial thermoplasty (BT), again without clinical benefit. Since our patients met the AIFA criteria for inclusion in mepolizumab treatment, a therapy with this anti-IL5 biological agent was initiated. In the first case (a 53-year-old female), after the second mepolizumab administration, symptoms improved progressively, with a reduction in the number and severity of exacerbations, so the patient could finally be discharged from hospital. At follow-up, it was possible to reduce oral corticosteroids and continuing with inhaled corticosteroids/long-acting beta-agonists and montelukast. The patient had only one exacerbation/year. Symptom control and quality of life improved significantly. In the second case report (a 55-year-old male), after the sixth mepolizumab administration, symptoms improved progressively, with a reduction in the number and severity of exacerbations. At follow-up, it was possible to reduce and stop oral corticosteroids, continuing with inhaled therapy and montelukast. Symptom control and quality of life improved significantly.These are the first cases of patients unresponsive to sequential omalizumab and BT but with good and prolonged clinical response to mepolizumab. Both cases suggest that also after the failure of two consecutive third-line treatments, a third treatment (mepolizumab) should be attempted.

Canadian multidisciplinary expert consensus on the use of biologics in upper airways: A Delphi study

“…A multicentre clinical trial (OSMO) demonstrated switching to an anti-eosinophil biologic in asthmatic patients was safe and efficacious in improving asthma control, healthcare utilization and exacerbations, even without an omalizumab washout period [ 50 ]. In several other case series, patients with severe allergic asthma demonstrated improved symptom control and a reduction in asthma exacerbations and severity after switching from omalizumab to mepolizumab [ 101 ]. As biologics target different inflammatory receptors and cytokines, patients with a suboptimal response to omalizumab might benefit from an anti-eosinophil agent, depending on their treatable traits.…”

Switching between biologics in severe asthma patients. When the first choice is not proven to be the best

“…Recently, a small number of case reports describing successful switching between biologics in severe asthma patients have been published 40‐43 . These reports mainly included patients eligible for both anti‐IgE and anti‐IL‐5 treatments and, due to the different time points these biologics became available to the market, they mainly describe alterations from omalizumab to mepolizumab 40,41 from omalizumab to benralizumab, 42 and from mepolizumab to benralizumab 43 .…”

“…Recently, a small number of case reports describing successful switching between biologics in severe asthma patients have been published 40‐43 . These reports mainly included patients eligible for both anti‐IgE and anti‐IL‐5 treatments and, due to the different time points these biologics became available to the market, they mainly describe alterations from omalizumab to mepolizumab 40,41 from omalizumab to benralizumab, 42 and from mepolizumab to benralizumab 43 . The results of a recent post hoc meta‐analysis of pooled data from ‘Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma’, (MENSA) 44 and’Mepolizumab adjUnctive therapy in subjects with Severe eosinophilic Asthma’ (MUSCA) 45 studies indicate that mepolizumab reduced exacerbation frequency and improved HRQoL and asthma control in patients with severe eosinophilic asthma, irrespective of prior omalizumab use 46 .…”

Efficacy of tezepelumab against uncontrolled severe non‐type 2 asthma refractory to bronchial thermoplasty, benralizumab, dupilumab and mepolizumab

“…Severe asthma is defined as asthma that remains uncontrolled despite treatment with high‐dose inhaled corticosteroids (ICS) and long‐acting β2‐agonists 1 . Bronchial thermoplasty (BT) can control severe asthma by reducing the amount of smooth muscle in the bronchial wall 2,3 . Furthermore, several clinical studies have shown that biological treatments, such as humanized monoclonal antibody against IL‐5 receptor α (benralizumab), humanized antibody against IL‐4Rα (dupilumab), and humanized monoclonal antibody against interleukin‐5 (IL‐5) (mepolizumab) are effective in severe asthma 1 .…”

“… 1 Bronchial thermoplasty (BT) can control severe asthma by reducing the amount of smooth muscle in the bronchial wall. 2 , 3 Furthermore, several clinical studies have shown that biological treatments, such as humanized monoclonal antibody against IL‐5 receptor α (benralizumab), humanized antibody against IL‐4Rα (dupilumab), and humanized monoclonal antibody against interleukin‐5 (IL‐5) (mepolizumab) are effective in severe asthma. 1 Tezepelumab is a human IgG2 monoclonal antibody that inhibits thymic stromal lymphopoietin (TSLP).…”