Dupilumab may offer relief for patients with eosinophilic otitis media (EOM) and severe chronic rhinosinusitis with nasal polyps (CRSwNP), according to investigators.

Over 12 months, the agent improved both sinonasal outcomes and otologic outcomes, including the Chronic Otitis Media Outcome Test 15 value (COMOT-15), which showed a median decrease from 49 to 15, reported lead author Cosimo Galletti, MD, of the Kore University of Enna, Enna, Italy.

“This study is important in that it provides additional evidence that biologic medications aimed at type 2 inflammation, such as dupilumab, can also have positive effects on middle ear disease,” said Theodore A. Schuman, MD, director of rhinology and skull base surgery at Virginia Commonwealth University, Richmond, Virginia, who was not involved in the study.

The study was published in the American Journal of Rhinology & Allergy.

Study Background and Design

Dupilumab has previously shown efficacy for severe CRSwNP in both randomized trials and real-world populations, according to the investigators, so sinonasal improvements are expected in suitable patients.

“The more novel clinical question is whether dupilumab also improves EOM-related outcomes,” the investigators wrote.

They aimed to address this gap with a multicenter retrospective observational cohort study, which involved 48 adults with severe CRSwNP and concomitant EOM treated at four tertiary otorhinolaryngology centers in Sicily, Italy. 

Patients received dupilumab 300 mg every 2 weeks, with outcomes evaluated at baseline, 6 months, and 12 months. Otologic outcomes were primary and sinonasal outcomes secondary.

Results

Over 12 months, median COMOT-15 (scored 0-75) decreased from 49 to 15 (P < .0001). At baseline tympanometry, 32 patients had type B patterns and 16 had type C patterns; by 12 months, 36 patients had type A tympanograms and 12 had type C tympanograms. No patients were downgraded to a lower category.

Sinonasal outcomes also improved, including median SNOT-22, which decreased from 68 to 22; median Nasal Polyp Score, which decreased from 6 to 2; and visual analog scale of nasal congestion, which decreased from 8 to 1 (all P < .0001).

Peripheral eosinophil counts did not change significantly.

Building on a Known Body of Evidence

“This is consistent with observational findings from our own research and makes sense from a unified airway perspective,” Schuman said.

Zara M. Patel, MD, chief of the Division of Rhinology at Stanford University School of Medicine, Stanford, California, applauded the authors for their investigation but noted that the findings do not reflect a new concept.

“We have many studies demonstrating that controlling inflammation in the sinonasal tract can help bring down inflammation within the middle ear space,” said Patel, who was not involved in the study.

“It makes logical sense that the inflammatory disorder affecting the sinonasal mucosa doesn’t stop at the back of the nose, but likely involves the respiratory mucosa of the nasopharynx, Eustachian tube, and middle ear,” Schuman said.

Schuman cautioned that the retrospective, observational design and small population size limit what can be concluded from the present study.

“It adds to the emerging body of evidence that anti-Th2 biologics help with eosinophilic middle ear disease, and certainly makes sense from a mechanistic standpoint, but properly designed clinical trials would be needed to better assess the effect of dupilumab on ear function and also compare it to other existing treatments,” Schuman said.

Galletti and colleagues acknowledged these limitations in the publication. They declined to comment.

Spotting Ear Disease in the Clinic

Schuman recommended routine office otoscopy, ideally pneumatic otoscopy, for every patient with sinonasal complaints, calling it “a quick, painless, cost-effective, and logical place to start.” Tympanic membrane retraction and middle ear effusion show up quickly, he added.

Patel pointed instead to patient-reported outcome measures, noting that the SNOT-22 already captures ear symptoms.

“It is always good to be aware of all symptoms and to make sure you are treating the whole patient,” Patel said.

When to Start a Biologic

Dupilumab is not approved for any ear-specific diagnosis, Patel noted, so prescribing rests on the CRSwNP indication.

“So if they have [CRSwNP], and also happen to have EOM, then certainly you could choose to prescribe it, but you cannot use [EOM] as the primary reason,” she said.

Schuman said he would be “very quick to start a biologic like dupilumab” in a patient with severe asthma and difficult-to-control CRSwNP who also had refractory middle ear disease. He would be more likely to stick to conventional treatments, he said, for patients with EOM lacking significant inflammatory airway disease.

Patel noted that most patients with underlying sinonasal disease “can do very well with thorough, complete sinus surgery followed by topical steroid therapy, and never need to progress to using biologics,” she said, adding that “all major societies that treat upper airway inflammation” are aligned on that strategy.

About 10%-15% of patients are not well controlled after that two-step process, she said, and those are the ones who stand to benefit from dupilumab or another biologic.

“A major reason why some allergists and primary care doctors opt to start patients on biologics first, despite the need for lifelong use and the exceedingly high cost, is that they have seen patients who underwent surgery that was not thorough and complete, and these patients have failed to resolve,” Patel said. 

The study received no outside funding. The authors reported no conflicts of interest. Schuman and Patel reported no relevant conflicts of interest.