In the early 1900s, researchers found a link between being sensitive to aspirin and getting asthma or nasal polyps. Today, this classic triad of symptoms is known as aspirin-exacerbated respiratory disease (AERD). About 0.3–0.9% of the USA population has AERD. Its symptoms usually come on slowly, starting with stuffy and runny noses and worsening to hyposmia, nasal polyps’ growth, and chronic rhinosinusitis (CRS). Asthma usually appears two years after the first respiratory symptoms. Disease management involves medicine and surgery, such as aspirin desensitization (AD), topical and systemic corticosteroids, and endoscopic sinus surgery. But the fact that AERD didn’t respond well to the usual treatments made for a new problem.
Biologics that target type II cytokines, cytokine receptors, and IgE have recently been approved for asthma and CRS: Dupilumab (targeting Interleukin [IL]-4 and IL-13) in June 2019; Omalizumab (anti-IgE) in December 2020; and Mepolizumab (anti-IL-5) in June 2021. They seem like good ways to treat AERD, but there isn’t much information to help choose the right agent.
To find out how dupilumab affects sinonasal and asthma outcomes in AERD in a unique way, researchers from the Department of Otolaryngology at Thomas Jefferson University conducted a retrospective study (2011-2022) on patients who had failed other biologics. At the recent American Rhinologic Society (ARS) 68th annual meeting, held from September 9, 2022, through September 10, 2022, in Philadelphia, PA, the researchers presented the funding in the poster “Impact of dupilumab on sinonasal and asthma outcomes in patients with aspirin-exacerbated respiratory disease (AERD) refractory to alternative biologics.”
This study included a total of 17 patients. Twelve patients (70.6%) tried one other biologic, 4 (23.5%) tried two, and 1 (5.9%) tried three. Eight, or 47.1%, underwent aspirin desensitization before switching to biologics. Three indicators evaluated the nasal symptoms and asthma outcomes. The 22-item Sinonasal Outcome Test (SNOT-22) score is a patient-reported outcome measure commonly used in rhinology/otolaryngology clinics to assess sinonasal symptoms. The Asthma Control Test (ACT) gives a score that medical professionals can use to figure out if asthma symptoms are well controlled. Forced expiratory volume in one second, or FEV1, is the most air you can forcefully let out of your lungs in one second. It describes how much asthma is blocking the airways, as measured by spirometry.
After one year of dupilumab treatment, the patient’s mean SNOT-22 scores went from 44.07 to 21.71, which significantly improved (p=0.002) for nasal polyps. For asthma outcomes, ACT scores improved, while FEV1 didn’t change significantly. This is the first evidence that AERD patients may benefit from dupilumab, even if they don’t respond completely to other biologics: the previous biological agent-controlled asthma symptoms pretty well, but dipulumab controlled sinus symptoms better.
“AERD may have subgroups with different sinonasal inflammatory patterns. Recent genetic studies on arachidonic acid 15-lipoxygenase (ALOX15) gene may explain some of these differences,” Dr. Glen D’Souza, the speaker, introduced, “More and more evidence show that IL-4 and IL-13 turn on STAT-6 to induce ALOX15 expression. It is reasonable to propose that dupilumab, as an IL-4 and IL-13 blocker, can inhibit ALOX15-related inflammation in AERD, but more research is needed to prove it.”