D1.152 - Treatment-induced remission after mepolizumab discontinuation: case series

Asthma remission represents the most desirable treatment outcome. While drug-free remission remains unpredictable, treatment-induced remission reports are increasing. Complete remission criteria include: absence of exacerbations requiring systemic corticosteroids (SCS) for ≥12 months, ACT ≥20 points, FEV1 ≥80% predicted. Limited data exist regarding disease-modifying effects of biologics, characterized by sustained improvement following treatment, including after discontinuation.

We present four cases demonstrating potential disease-modifying effects during mepolizumab therapy and after discontinuation. Written informed consent for publication was obtained from all patients. We followed four patients aged 32-41 years (2 males, 2 females) with severe uncontrolled atopic asthma and polysensitization. All developed asthma in early childhood (3-6 years) with severe course—multiple exacerbations including SCS use up to twice yearly, poor control (ACT ≤16-18), and eosinophilia >300 cells/μL. At mepolizumab initiation, all received maximum-dose ICS/LABA combinations. Anti-IL-5 biologic mepolizumab was added within phase 3 study MEA112997 (NCT01691859). Patients enrolled in 2012 with reduced lung function (FEV1 48-67% predicted). During mepolizumab therapy, marked improvement occurred with FEV1 normalization and complete/partial control (ACT 23-25) in all. Two patients had no exacerbations; one had 2 exacerbations (one requiring SCS); another had 1 exacerbation managed with nebulized therapy. All independently halved ICS doses due to sustained symptom control.

Patient P. (born 1991) discontinued mepolizumab in 2016. Currently uses budesonide/formoterol 160/4.5 μg as needed. No exacerbations, FEV1 87%, ACT 24.

Patient T. (born 1984) discontinued mepolizumab in 2014 due to non-tuberculous mycobacterial infection. Uses budesonide/formoterol 320/9 μg twice daily—no severe exacerbations; mild exacerbations 2-3 times yearly managed with nebulized therapy. FEV1 79%, ACT 21.

Patient N. (born 1989) discontinued mepolizumab in 2015 voluntarily. Uses fluticasone propionate/salmeterol 250/25 μg twice daily—no severe exacerbations; mild exacerbations twice yearly managed with nebulized therapy. FEV1 83%, ACT 24.

Patient Sh. (born 1983) discontinued mepolizumab in 2016. Uses budesonide/formoterol 160/4.5 μg twice daily—no exacerbations. FEV1 92%, ACT 23.

All achieved complete or partial remission (three complete, one partial) following mepolizumab discontinuation and ICS dose reduction, suggesting disease-modifying effects. Despite initially uncontrolled asthma, all maintained normal BMI and regular physical activity (CrossFit, equestrian, yoga, football), restored during therapy and maintained to present. Post-discontinuation exacerbations required no SCS. All four patients had at least one healthy child after mepolizumab discontinuation, supporting data on absence of reproductive toxicity. Our observations cannot definitively identify predictive patient characteristics due to small sample size. However, these data may prove valuable as similar cases accumulate, enabling better identification of patients with highest remission probability.