Mepolizumab cuts exacerbation, hospitalization and corticosteroids exposure in a young patient with severe Th2 asthma and marginal BEC level

Presentation, history and prior treatment
A 36-year-old Caucasian over­weight female banker with increas­ingly severe allergic and asthma symptoms presented to our clinic in late October 2024, after consult­ing multiple doctors in the US and UK for many years. She had been a smoker since the age of 24 years and switched to vaping 18 months before presentation and was advised to stop smoking. Since a young age, she had frequently experienced shortness of breath on minimal exertion, sports-induced asthma and respiratory tract infections.

Despite being on triple combi­nation maintenance therapy with inhaled corticosteroid (ICS)/long-acting β-agonist (LABA)/long-acting muscarinic antagonist (LAMA), she had four episodes of severe asthma exacerbations with three requiring hospitalization in the past year. She received short-term oral corticoste­roids (OCS) 20–40 mg daily for about 10 days per exacerbation episode. (Table)

The patient had a history of si­nusitis and recurrent rhinoconjunc­tivitis managed with antihistamines and corticosteroid nasal sprays, as well as various allergies (eg, house dust mites, tree and grass pollen) that were poorly controlled despite 5 years of immunotherapy. She was also allergic to erythromycin, cefu­roxime and levofloxacin. The exac­erbation episodes were possibly trig­gered by work stress on top of poorly controlled underlying allergies and asthma.

Chest X-ray report was unremark­able. Blood tests were positive for My­coplasma pneumoniae immunoglobulin (Ig) G antibodies, confirming intercur­rent infection history, but negative for bacteria on pneumoniae multiplex poly­merase chain reaction panel test. Blood eosinophil count (BEC) at various time points ranged between 150 and 300 cells/μL, depending on her clinical con­dition. Her IgE level was not elevated, and vitamin D level was slightly low.

Based on her phenotypic man­ifestations and blood test results, the patient was diagnosed as having adult-onset T-helper 2 (Th2) cough variant asthma, with bronchial hyper­responsiveness and allergic rhinitis.

Anti–IL-5 treatment and response
In addition to suboptimal re­sponses to conventional asthma and allergy treatments, concern re­garding cumulative corticosteroid doses and long-term adverse effects (such as increased body weight, and mood swings that required treat­ment with alprazolam) called for a corticosteroid-sparing therapy.

In November 2024, after in-depth discussion with the patient, treatment with mepolizumab began. Although me­polizumab is shown to be generally safe and well tolerated, the patient was ad­mitted for inpatient administration of the first dose as a precautionary measure for close monitoring of possible adverse reactions, given her history of allergies and as she was not feeling well at that time. Her slight vitamin D deficiency was concurrently treated to further reduce her susceptibility to upper respiratory tract infections and exacerbations.

After the first dose of mepolizum­ab, the patient reported immediate symptom improvement. She was then discharged from hospital with month­ly subcutaneous (SC) mepolizumab injection pens. Her frequency of clinic visits decreased from twice monthly to once every 2–3 months. Notably, the frequency of moderate-to-severe exacerbations decreased from four episodes per year to zero. (Table)

Her cough, rhinosinusitis and mood swings also improved, and she has not required any OCS since start­ing mepolizumab. Her inhaled treat­ment de-escalated from triple thera­py to dual therapy with ICS/LABA.

The patient tolerated mepoli­zumab well and did not report any adverse effects. Last seen in May 2025, she had stable disease, with well-controlled symptoms maintained on mepolizumab 100 mg Q4W. She reported marked improvement in quality of life (QoL). (Table)

Discussion
At the time of presentation, our patient had poorly controlled symp­toms and frequent exacerbations re­quiring hospitalization despite receiv­ing Global Initiative for Asthma (GINA) Global Strategy for Asthma Manage­ment and Prevention Step 4–5 rec­ommended treatment.¹

While she was responsive to OCS, cumulative corticosteroid dos­es (estimated at a minimum of 2 g over the last 20 years) and the asso­ciated long-term adverse effects are serious concerns, given the potential for further exposure if her condition remains refractory. A fundamental change in management strategy to an OCS-sparing and effective agent was therefore necessary.

Mepolizumab, an anti–interleukin (IL)-5, was chosen for our biologic-naïve patient based on her eosino­philic/type 2 (T2) inflammation phe­notypical symptoms with only mod­erately high BEC (150–300 cells/μL) – a profile similar to the T4 cluster of a subset of patients in the U-BIOPRED (Unbiased Biomarkers for the Pre­diction of Respiratory Disease Out­comes) study. My positive experience with mepolizumab, and its effective­ness and safety profile also contrib­uted to choosing this agent.²

This decision was supported by the latest GINA guidelines, which recommend biologics targeting T2 inflammation as add-on therapy (if available/affordable) after establish­ing severe asthma phenotype in the final management step (Step 5). Se­vere asthma is defined in the GINA guidelines as poor symptom control and frequent exacerbations despite maximal optimized high-dose ICS/LABA treatment and management of contributory factors, or that wors­ens when high-dose treatment is decreased. GINA has also acknowl­edged that use of mepolizumab reduces risk of severe disease ex­acerbation irrespective of baseline fractional exhaled nitric oxide (FeNO), improves QoL, and reduces need for OCS.¹

Mepolizumab directly inhibits IL-5, a key cytokine generated in T2 in­flammation. This reduces the number of eosinophils and other inflammatory cells such as neutrophils, basophils, mast cells and fibroblasts in circula­tion and tissue sites. IL-5 inhibition also modifies T cells and IL-C2 cells, which, together with positive effects on epithelial cells within the respi­ratory system, curbs the underlying disease processes in severe Th2 asthma, paving the way for restored immune balance and epithelial integ­rity, reduced mucus plugging and re­versal of airway remodelling, thereby reducing exacerbations as well as the need for OCS.^3-11

Post-hoc subanalyses of the REALITI-A study, which assessed mepolizumab’s real-world effective­ness in 822 patients with overlapping allergic and eosinophilic phenotypes, confirmed that SC mepolizumab 100 mg Q4W reduces clinically significant exacerbations irrespective of base­line BEC, FeNO, IgE or prior omali­zumab use.^12,13

Early use of biologics not only re­duces exacerbations, but also helps preserve lung health.^14,15 In the real-world observational CHRONICLE study in US adults with severe asth­ma, initiating biologics <3 years from severe asthma onset led to numeri­cally greater reductions in annualized exacerbations (72 vs 49 percent) than starting after ≥3 years.¹⁴ (Figure)

Exacerbations are associated with greater lung function decline over time. Early treatment that halts damage-causing underlying biolog­ical processes and interrupts airway remodelling may prevent disease progression and serve as a potential disease-modifying strategy.

The post-hoc analysis of the real-world REDES study assessed the effectiveness and safety of SC mepo­lizumab 100 mg Q4W for 12 months in 318 patients with severe asthma in Spain. At baseline, patients with shorter vs longer asthma duration had significantly better lung function. In addition, at 12 months after start­ing mepolizumab, the proportion of patients achieving prebronchodilator forced expiratory volume in 1 second (FEV₁) normalization (≥80 percent) was higher among those with shorter disease duration. These results sup­port early use of mepolizumab after asthma diagnosis to potentially help preserve lung function.¹⁵

Our patient’s repeated relocations led to fragmented care and prevent­ed earlier use of mepolizumab, which could have reduced exacerbations and improved her lung function.

Conclusion
Patient selection for mepolizumab treatment is not always clear-cut. While biomarker levels are a useful guide, it is important not to solely rely on them (in instances where they fall near or be­low standard treatment thresholds) to start treatment with biologics. Clinical decisions should instead be made tak­ing into consideration patients’ history and clinical symptoms, such as those of the case described, where mepoli­zumab proved effective despite BEC not being exceedingly high.

Trial results and real-world data show that mepolizumab reduces asthma exacerbations, improves QoL, minimizes the need for long-term OCS, and has a well-tolerated safety profile.