In reply: Aspirin desensitization for aspirin-exacerbated respiratory disease in the era of biologics: Clinical perspective

We read with great interest Dr Bosso’s recent correspondence.¹ In that communication he nicely describes the emergence of aspirin therapy after desensitization (ATAD), as type 2 biologics represent highly promising therapies in the treatment of our most recalcitrant patients. The rate of surgical revision among patients with aspirin-exacerbated respiratory disease (AERD) and other type 2–dominant forms of nasal polyps remain unacceptably high, highlighting our need for these complementary therapies.² We welcome the inclusion of these agents as part of our evidence-based approach toward the treatment of patients with recurrent nasal polyps.

Despite this enthusiasm, significant limitations remain that must be addressed to appropriately use both of these therapies to improve patient care. Trials of ATAD have been largely single-center reports without standardized methodology or consistent aspirin dosages, making direct comparison of results difficult. However, although the overall level of evidence supporting use of ATAD after revision endoscopic sinus surgery (ESS) remains strong, with multiple randomized, controlled trials and treatment recommendations supporting its broad utilization,^3,4 adoption remains critically low. More than 30% of surveyed allergists decline to offer ATAD as part of their clinical practice.⁵ This translates into a challenging situation with few providers and an estimated prevalence of aspirin desensitization as low as 7% among AERD patients seeking care in the United States.⁶ Despite the clear benefits of ATAD, additional work must be done to increase access to this procedure for our many patients with uncontrolled disease. The multidisciplinary care offered by Bosso et al at the University of Pennsylvania is one of the many examples of allergy/otolaryngology partnerships that must be further incorporated throughout both academic and private practice settings.⁷

Likewise, although type 2 biologics have a large body of evidence in support of their use for treatment of nasal polyps, substantial work remains to define their appropriate use in the clinical setting.⁸ There are currently 2 major deficiencies in the currently available evidence that we hope to see addressed in the near future. The first involves the timing of biologic therapy and indications for prescribing. Current pivotal trials supporting these therapies limit the use of biologics to the preoperative setting for patients with obstructive nasal polyps. Although outcomes of these rigorous studies have displayed clinically significant improvements in both polyp size and patient symptoms, the utilization of type 2 biologics before surgery has not demonstrated complete resolution of disease. It is therefore not uncommon for patients with improved symptoms to still seek ESS in hopes of further relief. Additional study is needed to clarify the appropriate indication for these important new therapies and answer the critical question of whether type 2 biologics, when used as a postoperative adjunct to appropriate ESS, contribute to long-term disease control in patients at high risk for recurrence.

Early studies have demonstrated the efficacy of several type 2 biologics for the treatment of heterogeneous populations with nasal polyps.⁹ However, additional study is needed to define the outcomes among patients with specific nasal polyp endotypes to improve patient care. At present, no phase 3 clinical trial has included patients with allergic fungal rhinosinusitis, thereby excluding patients from this severe form of disease from present US Food and Drug Administration indications. In addition, the reported efficacy of type 2 biologic therapy varies significantly by molecular target and is not universal to all patients with uncontrolled nasal polyps. It also remains to be seen whether we may anticipate a differential clinical response to biologic therapies based on the degree of type 2 inflammation, as has been shown in treatment of asthma. Further studies aiming to identify prognostic biomarkers associated with clinical response with each type 2 biologic and nasal polyp endotype will improve patient care.

The emergence of ATAD and type 2 biologics represents significant advancement in our ability to care for patients with the most recalcitrant forms of nasal polyps. As with any emerging therapy, rigorous study with thoughtful criticism must be completed to define patient-centered indications. It is only through a multidisciplinary approach with close collaboration between allergy and otolaryngology disciplines that we will be able to maximize the effect of these treatments and advance patient care. This is how health care is impacted for the better, and we are excited to play a small role along the way.