Biological treatments and biomarkers in asthma and nasal polyps

Posted: 28th August 2025 | Posted by AdminMR

Biological treatments and biomarkers in asthma and nasal polyps.

Recent developments in the management of asthma and related airway diseases have underscored the growing importance of early biologic therapy, particularly for patients with Global Initiative for Asthma (GINA) step 4 disease. While the application of biologics in GINA step 3 remains under evaluation, emerging registry data may broaden future indications. The rationale for early use is reinforced by the frequent occurrence of chronic rhinosinusitis with nasal polyps (CRSwNP) as a precursor to severe asthma, both conditions sharing type 2 (T2) inflammatory pathways that biologics effectively target.

Management strategies for non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) increasingly incorporate biologic therapies alongside traditional approaches. Initial treatment often combines inhaled corticosteroids, long-acting beta agonists, and leukotriene receptor antagonists. Escalation to T2 biologics, including anti–interleukin-5 and anti–interleukin-4 receptor antibodies such as dupilumab, is guided by peripheral eosinophil counts and the severity of concurrent rhinosinusitis.

A central theme in therapeutic evaluation is the distinction between clinical remission and cure remission. Clinical remission reflects disease control achieved while treatment is ongoing, whereas cure remission implies durable control after treatment discontinuation. True cure remission remains rare with biologic agents, with relapses frequently occurring within two to three months of cessation, as demonstrated in post-marketing studies of mepolizumab. In contrast, allergen immunotherapy—whether subcutaneous or sublingual—offers a greater likelihood of long-term remission beyond the treatment period, a distinction that highlights the limitations of biologics in achieving lasting disease modification.

Biomarker research is expanding the precision of treatment selection, particularly in allergen immunotherapy. Studies of Timothy grass immunotherapy have shown that variability in sensitisation profiles and IgG responses strongly influences clinical outcomes. Artificial intelligence–based tools are being developed to analyse complex biomarker datasets with the aim of predicting which patients are likely to respond to therapy. However, these approaches require further validation in large, prospective cohorts to overcome the heterogeneity of disease mechanisms and clinical endpoints.

The terminology surrounding remission remains unsettled, as biologic-induced remission differs fundamentally from that achieved after immunotherapy. Greater standardisation of definitions is needed to support consistent interpretation in both research and clinical practice. There is also growing interest in combining biologics with allergen immunotherapy, particularly for severe, mite-sensitised asthma, with the goal of achieving deeper and more durable disease modification. Current evidence, however, is preliminary.

Safety considerations remain an integral part of biologic therapy. Transient peripheral eosinophilia is a recognised effect of treatments such as dupilumab and is usually self-limited, though rare cases of eosinophilic granulomatosis with polyangiitis (EGPA) have been reported. Regional variation exists in thresholds for concern and intervention, underscoring the need for tailored monitoring protocols.

Looking forward, research is beginning to explore cell-based immunomodulatory therapies, including regulatory T lymphocyte–based strategies, though the systemic and polygenic nature of airway disease presents challenges not encountered in oncology. Insights from food allergy research, particularly studies of combined biologic therapy and immunotherapy in children, may provide valuable models for advancing asthma care.

Future priorities include strengthening collaboration between respiratory and ear, nose, and throat specialists to clarify the temporal links between CRSwNP and asthma, as well as designing adequately powered studies to test combination therapies. Efforts should also focus on refining eosinophil monitoring, standardising remission terminology, and validating biomarker algorithms in large, well-phenotyped cohorts to improve patient stratification and treatment outcomes.

References:

• Holguin F, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2020;55(1):1900588. doi:10.1183/13993003.00588-2019.
• Bachert C, et al. Biologics in chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2022;149(5):1443-1451. doi:10.1016/j.jaci.2022.02.017.
• Wechsler ME, et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2017;376(20):1921-1932. doi:10.1056/NEJMoa1702079.
• Shamji MH, et al. Biomarkers for immunotherapy in allergic disease. J Allergy Clin Immunol. 2017;140(6):1489-1498. doi:10.1016/j.jaci.2017.10.009.
• Agache I, et al. Artificial intelligence and biologicals for allergy. Allergy. 2023;78(2):471-478. doi:10.1111/all.15412.