Efficacy and Safety of Dupilumab in the Treatment of Severe Asthma Insufficiently Controlled by Standard Therapy – Current Clinical Practice Data
If severe bronchial asthma with type 2 inflammation is insufficiently controlled by combined maintenance therapy, dupilumab – a recombinant monoclonal antibody inhibiting the signaling pathway of interleukins 4 and 13 – can be added. What is its efficacy in clinical practice? We summarize findings from 3 recent retrospective studies.
Early Efficacy of Dupilumab in the Treatment of Severe Asthma
A total of 12 patients (median age 64 years; 58% male) with severe asthma bronchiale insufficiently controlled by standard therapy were included in the Italian study (1). All had eosinophilia > 150 cells/ml and/or exhaled nitric oxide (FeNO) > 25 ppb in the last year. These patients were administered dupilumab subcutaneously in a loading dose of 400 mg and subsequently in a maintenance dose of 200 mg every 14 days.
After 3 months of therapy, significant improvement in disease control was observed. The asthma control test (ACT) score increased from 13.25 to 19.17 points (p < 0.01), relative forced expiratory volume in one second (FEV1%) from 62.58 to 71.00% (p < 0.01), and FeNO decreased from 32 to 19 ppb (p < 0.05). Lab results showed a numerical increase in eosinophils (from 280 to 350 cells/ml; p = 0.52) in blood. The increase in eosinophils was not statistically significant and had no clinical impact. A significant clinical difference (MCID) in FEV1% was achieved in 4 patients (33%), and in ACT in 8 patients (67%).
Efficacy of Dupilumab in Patients Previously Treated with Biological Therapy
The Austrian study (2) included a total of 13 patients (average age 47 years; 69% male). 85% of them had previously been treated with monoclonal antibodies (anti-IgE or anti-IL-5/IL-5R) without sufficient effect. Patients used dupilumab in the standard dosing regimen mentioned above.
After 2 weeks of therapy, the asthma control according to the ACQ-6 questionnaire improved by 0.57 points (p = 0.014) and after 4 weeks according to the ACT test by 3.91 points (p = 0.024). Both improvements were both statistically and clinically significant and maintained after 3 months of therapy. Statistically and clinically significant increases in forced expiratory volume in one second (FEV1) were observed after 4 weeks and 3 months from the start of therapy, increasing by 220 ml (p = 0.041) and 229 ml (p = 0.006), respectively.
During the therapy, no hypereosinophilia or severe treatment-related adverse events were reported. A total of 3 patients (23%) were concurrently using oral corticosteroids, and all could reduce their dose by at least 50% after 3 months due to dupilumab.
Efficacy and Safety of Dupilumab in Patients with Severe Asthma
The Dutch study (3) included a total of 148 patients with severe asthma insufficiently controlled by standard therapy between January 2019 and December 2020 (median age 52.5 years; 38.5% male). Patients again used dupilumab according to the standard dosing regimen.
After 12 months of therapy, the annual frequency of exacerbations decreased from 4.0 to 1.0 (p < 0.001), with 46% of patients being exacerbation-free for 12 months. This corresponded to improved asthma control according to the ACQ-5 questionnaire from 3.0 to 1.8 points after 6 months, and to 1.4 points after 12 months of therapy (p < 0.001). The necessity to use oral corticosteroids in maintenance therapy decreased from 39.9% of patients to 20.3% after 6 months and 14.9% after 12 months of therapy (p < 0.001). Significant improvements in FEV1 from 2.21 to 2.50 liters after 6 months and to 2.51 liters after 12 months of therapy (p < 0.001) were also observed. The best results overall were observed in the subgroup with marked eosinophilia (i.e., ≥ 300/µl) or a high FeNO (i.e., ≥ 50 ppb).
Treatment-related adverse events were reported in 45.3% of patients (n = 67). The most common issues were headaches, flu-like symptoms, eye complaints, and injection site reactions.
Summary and Discussion
According to the mentioned studies, dupilumab in patients with insufficiently controlled severe asthma early improves asthma control, already within 2 weeks to 3 months. Lung function (increase in FEV1) and FeNO improve and patients become less dependent on oral corticosteroids during therapy. Dupilumab is also suitable for patients who insufficiently responded to anti-IL5/IL-5R or anti-IgE biological treatments. However, the first two cited studies are limited by the small number of participants and larger prospective studies with longer follow-up periods will be necessary in the future.
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Sources:
1. Carpagnano G. E., Scioscia G., Buonamico E. et al. Early effectiveness of type-2 severe asthma treatment with dupilumab in a real-life setting; a FeNO-driven choice that leads to winning management. Multidiscip Respir Med 2022; 17 (1): 797, doi: 10.4081/mrm.2022.797.
2. Renner A., Marth K., Patocka K. et al. Dupilumab rapidly improves asthma control in predominantly anti-IL5/IL5R pretreated Austrian real-life severe asthmatics. Immun Inflamm Dis 2021; 9 (3): 624–627, doi: 10.1002/iid3.434.
3. Thelen J. C., van Zelst C. M., van Brummelen S. E. et al. Efficacy and safety of dupilumab as add-on therapy for patients with severe asthma: a real-world Dutch cohort study. Respir Med 2023; 206: 107058, doi: 10.1016/j.rmed.2022.107058.
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