16-year-old can breathe again

Physicians from the Department of Otorhinolaryngology at the University Hospital of Giessen and Marburg were dealing with a 16-year-old patient with a particularly pronounced chronic rhinosinusitis with nasal polyps (CRScNP) with comorbid bronchial asthma and NERD. Presentation was for anosmia and nasal obstruction bilaterally with displacing polyposis nasi.

In the past, the teenager has had four sinus surgeries, most recently at age 13. However, a pronounced local recurrence occurred only a few months after surgery despite local and repeated systemic cortisone therapies. After taking aspirin, novalgin, and ibuprofen, an asthma exacerbation occurred, and clinically, there was a shifting polyposis nasi bilaterally, filling almost the entire nasal cavity.

A Sniffin’ Sticks test showed functional anosmia with an SDI score of 11. Asthma was well controlled with fluticasone/vilanterol (asthma control test: 22 of 25 points). The most recent cross-sectional imaging was performed in June 2017 with an image of polypous pansinusitis. Cystic fibrosis was already ruled out by molecular genetic diagnostig in 2013.

The physicians from the University Hospital Giessen and Marburg started a therapy with dupilumab (300mg in biweekly subcutaneous administration) in combination with twice-daily mometasone nasal spray (100 μg per nostril) in May 2020. The declaration of cost coverage by the health insurance company is initially limited to 6 months. Every time an injection is given, the patient is presented to the clinic for a check-up with endonasal video endoscopy.

Improvement already after 2 weeks

Both CRSwP and NERD often involve type 2 inflammation with eosinophilia and elevated serum IgE, which is maintained via the release of IL-4, IL-5, and IL-13 from the namesake type 2 T helper cells (Th2) and lymphocytic cells of the innate immune system (ILC2). Dupilumab blocks the IL-4 and IL-13 receptors, thereby specifically inhibiting the type 2 inflammatory response.

Already 2 weeks after initiation there was a significant regression of the polyps and improvement of nasal breathing. During the course of the study, the extent of polyposis was fluctuating with an overall significant decrease of polyps and subjectively constant good nasal breathing. The sense of smell was subjectively perceived by the patient as improved only for a short time. This sensation was also reflected in the Sniffin’ Sticks test: with an SDI value of 20.5, there was only hyposmia after 6 weeks, but after 16 weeks, with an SDI value of 13, it again approached the baseline value of 11 and worsened to functional anosmia. Nevertheless, the 16-year-old’s quality of life (determined by Sinunasal Outcome Test 22, SNOT-22) improved from 25 points pretherapeutically to 10 points after 8 doses. The asthma improved subjectively already after the first administration of dupilumab with greater exercise tolerance. The on-demand spray (salbutamol) no longer had to be taken.

Use justified

In this case of CRScNP that could not be controlled with previous treatment options, with locally severe findings, unusually early onset of disease, a high tendency to recurrence, and NERD, the off-label use of dupilumab is justified despite the young patient age, the physicians explain. In 2019, dupilumab was approved for the treatment of CRScNP as an add-on therapy to cortisone-containing nasal spray when adequate control could not be achieved with surgery and/or systemic cortisone therapy. This approval is limited to adults 18 years of age and older. Dupilumab is approved for the treatment of chronic urticaria and bronchial asthma from the 12th year of life.

After 16 weeks, there has already been a significant improvement in complaints with a low risk profile. However, they caution that it remains to be seen whether long-term symptom freedom can be facilitated, as fluctuating polyp and olfactory findings are already being observed. The duration of therapy is currently not foreseeable; based on the phase III studies SINUS-24 and SINUS-52, a renewed increase in the size of the polyps is to be expected after discontinuation. In the course, ASA deactivation and revision pansinus surgery is possible as an alternative or additive to dupilumab administration. Data on possible synergistic effects of the different therapeutic modalities are not available.

Source: German Allergy Congress 2020, Wiesbaden (D)

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