EAACI Guidelines for the Use of Biologic Therapies in Severe Asthma

Targeted therapy with 1 of 5 available biologic medications may effectively manage severe asthma, according to treatment guidelines published by the European Academy of Allergy and Clinical Immunology (EAACI) in Allergy.

Although severe asthma remains burdensome for patients and may prove difficult to manage, elucidation of some of the complex pathogenetic immunoinflammatory mechanisms underlying the heterogeneous clinical presentation of this condition, along with development of biologic therapies targeting involved pathways — type-2 (T2) high, T2 low and mixed endotypes — have provided clinicians with an enhanced armamentarium.

EAACI recommendations are based on available evidence as well as clinical expertise and follow the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. These recommendations deal with treatment of severe asthma with 5 monoclonal antibody treatments: benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab.

Recommendations are provided for patients with 3 types of severe asthma: eosinophilic asthma, allergic asthma, and severe T2 asthma. The primary outcomes examined in the systematic literature reviews conducted included severe exacerbations of symptoms, treatment safety issues, results of the asthma control test, and answers to the asthma control and asthma quality of life (QoL) questionnaires. Other outcomes considered were lung function using the forced expiratory volume in one second and changes in medication regimen.

In adult patients with severe eosinophilic asthma that is uncontrolled despite background controller medication, benralizumab, an interleukin-5 inhibitor, is strongly recommended as add-on therapy to reduce severe exacerbations and taper oral corticosteroids (OCS) when the blood eosinophil count is >150/µL. In addition, benralizumab is conditionally recommended as safe and effective for the improvement of lung function, disease control, and QoL. Benralizumab is also conditionally recommended as add-on therapy for patients aged 12 to 17 years with severe uncontrolled eosinophilic asthma and adults with uncontrolled severe allergic asthma.

For the treatment of adults and adolescents aged 12 to 17 years with uncontrolled severe eosinophilic asthma despite the use of controller medications, dupilumab, which blocks interleukin (IL)-4, is strongly recommended as add-on therapy to reduce symptom exacerbation and improve lung function.  Dupilumab is conditionally recommended as safe and effective for the improvement of asthma control and QoL and the reduction of the need for rescue medications. The use of dupilumab is also conditionally recommended as add-on therapy for adults and patients aged 12 to 17 years with severe uncontrolled allergic asthma to enhance lung function and disease control while limiting severe exacerbations. In addition, dupilumab can be used as an add-on to treat severe uncontrolled T2 asthma in both age groups, is strongly recommended to reduce exacerbations, increase lung function, and taper OCS, and conditionally recommended to improve QoL and asthma control and reduce the reliance on rescue medication.

Mepolizumab, an IL-5 inhibitor, should be considered as add-on therapy in adults with severe uncontrolled eosinophilic asthma despite the use of controller medications. The medication is accompanied with strong recommendations to limit exacerbations and taper OCS, and conditional recommendations regarding safety (after parasitic infection screening) to improve lung function, disease control and QoL. This biologic can also be used as an add-on to treat adolescents aged 12 to17 years taking controller medications who still have severe uncontrolled eosinophilic asthma, with conditional recommendations regarding all outcomes.

Adult patients with both allergic and nonallergic severe uncontrolled eosinophilic asthma despite optimal controller therapy may benefit from the addition of omalizumab, which reduced T2 cytokine production. Omalizumab is strongly recommended to alleviate exacerbation in this patient population, and conditionally recommended as safe (with initial anaphylaxis monitoring) and effective for the improvement of lung function and QoL and the reduction of rescue medication use. Omalizumab may also be considered as add-on treatment in both adult patients and patients aged 12 to 17 years for moderate to severe allergic asthma that remains uncontrolled despite the use of background controller medications, with the same recommendations (and anaphylaxis caution) as those for severe eosinophilic asthma.

In addition, a conditional recommendation is given for the use of omalizumab to lower the use of inhaled corticosteroids (ICS). Omalizumab may be added to existing therapy for children aged 6 to 11 years with moderate to severe allergic asthma not controlled by background medications, with conditional recommendations for its use for the reduction of symptom exacerbations and ICS use and the improvement of asthma control and QoL.

Reslizumab is strongly recommended as add-on treatment for adults with severe uncontrolled eosinophilic asthma who are taking controller medications as a way to lower symptom exacerbations. It is also conditionally recommended as safe (with cautions regarding anaphylaxis monitoring and parasitic infection screening) and effective for the improvement of lung function, disease control, and QoL.

A 3-tiered algorithm that takes into account clinical phenotypes, disease-related outcomes and biomarker statuses, is provided to facilitate decisions of which biologic to initiate. None of the considered biologic medications had disease-modifying effects, and all had waning efficacy shortly after discontinuation.

“The addition of targeted treatment for severe asthma based on phenotyping has proved of real value,” the authors noted. “These recommendations should be reconsidered when new evidence becomes available and an update of these guidelines is planned for 2024.”

Reference

Agache I, Akdis C, Akdis M, et al. EAACI biologics guidelines – recommendations for severe asthma [published online June 2, 2020]. Allergy. doi:10.1111/all.14425