What Is the Next Step for Patients With Aspirin‐Exacerbated Respiratory Disease: Biologics With or Without Aspirin Therapy?

To date, there has been no consensus to guide the use of aspirin therapy after aspirin desensitization (ATAD) versus biologics or simultaneous use of both therapies in patients with aspirin-exacerbated respiratory disease (AERD). It should be clearly emphasized that biologic treatment of asthma and chronic rhinosinusitis with nasal polyps (CRSwNPs) is not an alternative to chronic use of aspirin after desensitization in patients with AERD. This opinion is also shared by the authors of a recent review [1]. According to the current guidelines for the management of asthma, biologics are reserved only for patients with severe asthma [2]. In the case of isolated CRSwNPs [3] without a diagnosis of asthma in most European countries, including Poland, the national payer accepts biologic treatment only after the recurrence of upper respiratory tract symptoms after two ineffective treatments with functional endoscopic sinus surgery (FESS). Therefore, from the point of view of asthma treatment, biologic drugs can only be used in patients with AERD who have severe asthma or have had two FESS treatments. On the other hand, ATAD can be introduced at any level of disease severity and control, regardless of whether the patient has upper or lower respiratory symptoms. It seems reasonable to consider the biologic treatment of AERD patients with severe asthma separately in future decisions. Patients who are treated with aspirin after desensitization and skip their dose for more than 3 days gradually become intolerant again and then need to be redesensitized to aspirin. It would be interesting to investigate this phenomenon during biologic therapy. Currently, it is unclear whether patients with AERD during biologic therapy (e.g., omalizumab) become tolerant to aspirin [4]. Looking at the definition of achieving drug tolerance, if tolerance to aspirin was achieved during biologic therapy, it would be possible to use aspirin chronically in AERD patients without aspirin desensitization. We cannot equate long-term aspirin therapy after aspirin desensitization with long-term aspirin therapy during biologic therapy. Current research only proves that some biologic drugs prevent bronchospasm after increasing doses of aspirin administered over several hours during a diagnostic test or reducing the provocative dose of aspirin causing aspirin-induced bronchospasm. Therefore, the conclusion regarding aspirin tolerance in some AERD patients during biologic treatment is too general. It appears that aspirin desensitization is necessary to achieve tolerance to aspirin. The best approach to the treatment of patients with severe AERD appears to be the concomitant use of a biologic drug and long-term high-dose aspirin therapy following aspirin desensitization. However, due to the greater clinical benefit of using biologics and the fewer side effects of these drugs compared with long-term high-dose aspirin therapy after aspirin desensitization, biologic therapy comes to the fore, especially in severe forms of AERD. In the era of biologic drugs, we suggest considering simultaneous biologic therapy and treatment with long-term low doses of aspirin after desensitization to maintain aspirin tolerance. For patients with AERD and high or very high cardiovascular risk, chronic low-dose aspirin was recommended as primary prevention before switching the patient from long-term high-dose aspirin to a biologic. A similar approach has been proposed for patients requiring cyclooxygenase-1 inhibitors for chronic pain and arthritis [5]. A therapeutic goal for AERD patients should be to achieve complete remission of all three conditions: (1) asthma, (2) CRSwNPs, and (3) aspirin hypersensitivity [1]. A proposed approach to biologic and ATAD treatment for AERD patients is presented in Figure 1, with updates and personalization of therapy in line with rapidly developing knowledge. According to current guidelines, the choice of therapy largely depends on the severity of the disease. This work was supported by the National Science Centre, Poland (Narodowe Centrum Nauki; Grant No. UMO-2020/39/B/NZ5/02296). The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.