Cycling biologic therapy with tezepelumab and mepolizumab for eosinophilic otitis media and eosinophilic pneumonia in a patient with asthma

Abstract

Sequential use of biologic therapies such as tezepelumab and mepolizumab may represent a steroid-sparing and effective treatment approach for managing distinct eosinophilic disorders, including eosinophilic pneumonia and eosinophilic otitis media, which may require distinct cytokine-targeted strategies.

Eosinophilic disorders are characterized by eosinophilic inflammation and differ substantially in clinical presentation, underlying pathophysiology, and treatment response.¹ When multiple eosinophilic conditions coexist in a single patient, management becomes more complex owing to organ-specific cytokine dominance.1, 2, 3

Biologics targeting type 2 inflammation—IL-5, IL-4/13, and thymic stromal lymphopoietin (TSLP)—have significantly improved outcomes in severe asthma and related eosinophilic diseases.^2,4, 5, 6, 7 However, in cases of multiorgan involvement, distinct cytokine drivers may limit the efficacy of a single biologic.¹ For instance, eosinophilic pneumonia (EP) is primarily IL-5–mediated, whereas eosinophilic otitis media (EOM) and chronic rhinosinusitis with nasal polyps are often driven by upstream cytokines such as TSLP and IL-4/IL-13.^2,4, 5, 6

Combination biologic therapy may seem ideal but is often impractical owing to high costs, lack of regulatory approval, and insurance restrictions.¹ Meanwhile, biologic cycling—the sequential use of different biologics—offers a flexible, personalized strategy for complex eosinophilic disease.^2,5

Here, we report a patient with asthma, recurrent EP, and refractory EOM who achieved corticosteroid-free remission through alternating administration of mepolizumab and tezepelumab every 3 months. This approach enabled cytokine-specific therapy for distinct disease sites while maintaining compatibility with the Japanese national health insurance system.

A 49-year-old woman with a history of seasonal allergic rhinitis since her early 20s that typically occurred during spring developed persistent cough and wheezing in her mid-40s. She had no history of childhood eczema or family history of allergic diseases, including asthma, atopic dermatitis, and allergic rhinitis. She was diagnosed with asthma at a local clinic based on clinical symptoms and spirometry findings indicating reversible airflow obstruction. Despite initial treatment with inhaled corticosteroids and bronchodilators, her respiratory symptoms gradually worsened. A few months later, she developed fever and dyspnea. Chest computed tomography revealed bilateral infiltrates. Bronchoalveolar lavage fluid showed an eosinophil percentage of 72.5%; testing of her peripheral blood showed a white blood cell count of 10,000/μL (with eosinophils comprising 27%). Her serum IgE level was elevated (609 IU/mL). The results of testing for allergen-specific IgE were positive for Japanese cedar pollen and negative for Aspergillus. Skin prick testing was not performed, and the patient had never received allergen immunotherapy. The results of testing for myeloperoxidase-specific antineutrophil cytoplasmic antibody were negative. Although asthma, nasal polyps, and EP can occur in eosinophilic granulomatosis with polyangiitis, it was considered unlikely because of the absence of vasculitic features, a negative result of testing for antineutrophil cytoplasmic antibody, and a stable long-term course without systemic involvement.

The patient was diagnosed with EP. Prednisolone treatment (40 mg per day) resulted in prompt symptom resolution. However, relapses occurred whenever the dose was tapered (to <10 mg per day), necessitating repeated corticosteroid treatment for 2 years, which in turn resulted in weight gain and insomnia.

During this period, the patient developed nasal obstruction and progressive bilateral hearing loss. Otolaryngologic evaluation revealed ethmoid sinus and bilateral aural polyps causing significant conductive hearing loss. Topical and systemic corticosteroids provided limited benefit.

Given the patient’s persistent airway inflammation, mepolizumab (100 mg every 4 weeks) was administered. Her EP and asthma control improved, and corticosteroids were discontinued. However, her otologic symptoms recurred, with persistent otorrhea, granulation tissue formation, and progressive hearing impairment. The referring otolaryngologist performed limited resection of the aural polyps and administered intratympanic corticosteroid injections, which provided temporary relief.

The patient was referred to our institution for evaluation of refractory EOM and control of her asthma and EP. Cytologic examination of the otorrhea fluid revealed abundant eosinophils (+++) with bilateral aural polyps. At that time, her paranasal sinusitis and EOM had worsened despite mepolizumab therapy. High-resolution computed tomography performed before initiation of tezepelumab administration captured the most severe disease stage (Fig 1). Pulmonary evaluation revealed recurrent cough and sputum production. The laboratory data included a white blood cell count of 5800/μL (eosinophil percentage 0.9%), serum IgE level of 1485 IU/mL, and fractional exhaled nitric oxide level of 108 ppb. Spirometry revealed a preserved FEV₁ value of 86.8% with reduced maximum midexpiratory flow (37.7%).

Fig 1.

Peripheral eosinophil counts and fractional exhaled nitric oxide (Feno) levels during cycling therapy with mepolizumab (Mepo) and tezepelumab (Teza). Representative computed tomography (CT) images show (1) pulmonary infiltrates during an EP flare and resolution, (2) bilateral aural polyps before and after treatment, and (3) paranasal sinus opacification improving after therapy.

Dupilumab was considered but ultimately avoided because of reports of paradoxic eosinophilia and eosinophilic granulomatosis with polyangiitis-like flares in patients with EP.⁸ Tezepelumab (210 mg every 4 weeks) was instead selected for its broader anti-inflammatory action and favorable safety profile (Fig 1).⁹

The patient’s nasal symptoms improved rapidly within 2 weeks, including resolution of obstruction and restoration of olfaction. However, after 5 doses of tezepelumab, she developed cough, low-grade fever, and malaise. Chest imaging revealed recurrent pulmonary infiltrates (Fig 1). Laboratory tests showed an eosinophil percentage of 16.6% (absolute count 1210/μL), C-reactive protein level of 5.9 mg/dL, and serum IgE level of 1919 IU/mL, consistent with EP relapse. During this period, the patient’s otorrhea decreased and her hearing improved.

Mepolizumab was reintroduced, resulting in prompt symptom improvement and resolution of pulmonary infiltrates. One month later, the patient’s eosinophil count decreased to 100/μL and her serum IgE level declined to 938 IU/mL. At that time, aural granulation tissue had regressed.

Recognizing that each biologic controlled different disease components, we alternately administered mepolizumab and tezepelumab every 3 months in rotation. This interval was selected based on insurance constraints and clinical observation that disease flares occurred after 4 to 5 months of continuous tezepelumab monotherapy but not within the first 3 months of either agent. Thus, this strategy allowed sustained disease control without overlapping biologic exposure. Under Japan’s universal health care system, concurrent use of 2 biologics is not reimbursed without exceptional justification owing to cost and safety considerations. Therefore, the cycling strategy allowed sequential targeting of distinct inflammatory pathways while maintaining affordability and minimizing risk.

Over more than 12 months of follow-up, the patient remained free of asthma or EP exacerbations. Her otologic and nasal symptoms were well controlled. Audiometry demonstrated stabilization and modest improvement in her hearing thresholds.

This case illustrates that biologic cycling can be an effective and pragmatic strategy for managing multiorgan eosinophilic disease involving distinct cytokine pathways. Tezepelumab, which targets TSLP, effectively controlled EOM and sinonasal inflammation but was insufficient for controlling IL-5–driven EP. Conversely, mepolizumab rapidly controlled pulmonary disease but inadequately addressed upper airway symptoms.

Although biologic cycling has been reported in asthma with chronic rhinosinusitis with nasal polyps or EOM,² this appears to be the first documented case involving EP with radiologic- and biomarker-supported responses. The 3-month alternation allowed each agent to exert maximal effect while reducing cumulative exposure and avoiding insurance barriers.

An important observation was the inverse response between disease sites: EOM improvement with tezepelumab coincided with EP worsening, and vice versa with mepolizumab. This underscores the importance of a precision medicine approach in eosinophilic disorders, with treatment tailored to cytokine dominance within each organ system.

From a health systems perspective, biologic cycling may offer a cost-effective alternative to combination therapy, especially in settings with restricted access or reimbursement.⁵ Although long-term data are lacking and prospective validation is needed, this case supports biologic cycling as a viable option in carefully selected patients.

Alternating biologic therapy based on cytokine targeting and organ-specific disease activity may offer a personalized, cost-effective approach for complex eosinophilic disorders. This case illustrates sustained corticosteroid-free control across multiple organs in real-world practice.

Ethical approval and consent. Ethical approval was not required for this study. Written informed consent for publication was obtained from the patient in accordance with local institutional requirements.

Disclosure statement

Disclosure of potential conflict of interest: O. Matsuno has received lecture fees from Sanofi, AstraZeneca, and GlaxoSmithKline. The rest of the authors declare that they have no relevant conflicts of interest.