Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Mepolizumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNOKHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary. METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

Positionspapier: Empfehlungen zur Anwendung von Mepolizumab bei chronischer Rhinosinusitis mit Polyposis nasi (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the paranasal sinus mucosa with eosinophilic inflammation as the most common endotype. The anti-IL5 antibody mepolizumab was approved for the treatment of severe CRSwNP in the EU in November 2021. METHODS: A literature search was performed to analyze the immunology of CRSwNP and determine the available evidence by searching Medline, Pubmed, and the German national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 12/2021 that investigated the effect of mepolizumab in CRSwNP were considered. RESULTS: Based on the international literature and previous experience, recommendations for the use of mepolizumab in CRSwNP in the German health care system are given by an expert panel on the basis of a documentation form. CONCLUSIONS: Understanding about the immunological basis of CRSwNP opens new non-surgical therapeutic approaches with biologics for patients with severe courses. Mepolizumab is approved since November 2021 for add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP who cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Dupilumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the nasal and paranasal mucosa. A Type-2 inflammation is described as the most common endotype. Since October 2019 the anti-IL-4/-IL-13 antibody dupilumab has been approved in Germany as an add-on therapy to intranasal corticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps, when systemic corticosteroids alone or surgery do not provide adequate disease control. While recommendations for the use of dupilumab in CRSwNP exist at both national and international levels, until now it has not been adequately established, how therapy should be monitored and when it should be discontinued in the German Health Care System. METHODS: A literature search was performed analyzing previous data on the treatment of CRSwNP with dupilumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to 05/2022 were included. RESULTS: Based on international literature and previous experience, recommendations are given by an expert panel for follow-up and possible therapy breaks, therapy intervals or termination of therapy when using dupilumab for the indication CRSwNP in the German health care system based on a documentation form. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens new non-surgical therapy approaches with biologics for patients with severe courses. The authors give recommendations for follow-up, possible therapy breaks, therapy intervals and a termination for dupilumab treatment as add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP that cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

[Ultrasonography in paranasal sinus disease (author's transl)]. / Les ultra-sons dans le diagnostic des affections sinusiennes.

Diagnostic A- and B-mode ultrasonography is used for detection of paranasal sinus disease. Various cases of maxillary, frontal and ethmoidal sinus pathology demonstrate the indication and limitations for this new method. Differential diagnostic of an opacified antrum is possible changing gain control and patients head position during examination.

[Provoking intranasal tests in frequent allergic rhinopathies (author's transl)]. / Les tests de provocation par voie nasale dans les rhinopathies allergiques courantes.

The intranasal test was made on 100 patients with possible allergy to house dust, house dust mite and fungi. The results of 64 patients could be discussed. Till now a nasal obstruction with arhinomanometric flow-volume diminution of 20% after application of allergene was considered as a positive provocation. This procedure seems to give too many false positive results. A new method to evaluate the rhinoma nometric results was elaborated.

[About rhinomanometric results with INT (author's transl)]. / Zur Beurteilung rhinomanometrischer Messergebnisse beim Intranasalen Provokationstest.

The Intranasal Test was made on 100 patients with possible allergy to house dust, house dust mite and fungi. The results of 64 patients could be discussed. Till now a nasal obstruction with a rhinomanometric flow-volume diminution of 20% after application of allergen was considered as a positive provocation. This procedure seems to give too many false positive results. A new method to evaluate the rhinomanometric results was elaborated.

[The expiratory second capacity of the nose--a new method to check the intranasal provocation test]. / Die exspiratorische Sekundenkapazität der Nase--eine neue Methode zur Kontrolle des Intranasalen Provokationstestes.

There are several methods presently in use serving to check the result of the intranasal provocation test. There are simple procedures such as rhinoscopy and cotton swabs as well as technically more cumbersome ones, such as rhinomanumetry. The FEV1 of the nose is a simple method used to evaluate the intranasal provocation test. The results obtained after allergy exposition are objective and reliable. This technique is equally as good as the above mentioned ones, and is not as expensive.

[The methodological and technical sources of error in the performance of the rhinomanometrically controlled intranasal provocation test (author's transl)]. / Methodische und technische Fehlermöglichkeiten beim rhinomanometrisch kontrollierten Intranasalen Provokationstest.

Nasal ventilation can be ascertained with the aid of rhinomanometry. In fact, even a trivial nasal allergic reaction can be detected through the use of the intranasal provocation test, coupled with rhinomanometrics. The different rhinomanometric measurement procedures, including determination of active and passive rhinomanometry, will be discussed in the following article. The advantages and disadvantages of each will be elaborated. The application of the active rhinomanometry however, invites not only certain technical errors but errors of method as well. These will be individually discussed in more detail.

[Long-term results of gentamycin therapy of Menière's disease]. / Langzeitergebnisse der Gentamicin-Therapie des Morbus Ménière.

During the years 1976 to 1987, 82 patients with Ménière's disease received a tympanoclysis with gentamicin on a daily basis. Dosage was titrated up to the initial symptoms of vestibular or cochlear intoxication. Sixty-four patients filed for a complete follow-up examination; it was possible to interview 15, while three patients were lost. Vertigo was eliminated in 70 (89%) cases. Nine patients (11%) remained disabled, while demonstrating typical paroxysmal positional vertigo in three cases. Speech discrimination improved in 13%, stabilized in 54%, and deteriorated in 33%. Hearing improved significantly better if, preoperatively, there had been low frequency loss rather than a flat audiogram. HALLPIKE's caloric test demonstrated residual vestibular activity in 72 percent. In the author's opinion, tympanoclysis with gentamicin offers a technically simple, riskless, and effective method to rehabilitate patients with disabling Ménière's disease.

[Diagnosis of inflammatory paranasal sinus diseases]. / Diagnostik entzündlicher Nasennebenhöhlenerkrankungen.

In chronic sinusitis allergy is one important factor for the pathogenesis of the disease. Various others, such as genetically determined or acquired ciliary disorders have to be ruled out. In allergic rhinosinusitis, allergy treatment improves postoperative results considerably.