Interleukins 4, 5 and 13 were shown to be important factors in type 2 inflammation, which characterises chronic rhinosinusitis with nasal polyposis (CRSwNP). In CRSwNP non-responders and those who recur short after-surgery monoclonal antibodies might be an answer. Examples include omalizumab (anti-IgE), mepolizumab (anti-IL 5) and finally dupilumab (anti IL 4, 13). The latter is approved for treatment of uncontrolled moderate to severe asthma in the EU and the US. It was also shown to improve patients with CRSwNP significantly in term of quality of life, endoscopic and radiological findings. Authors conducted a randomised, double-blind, placebo-controlled trial in the US and Europe. Patients included were 60 adults (18-65 years old), 30 controls and 30 with CRSwNP who failed two months of treatment with intranasal steroids. Patients should also have bilateral nasal polyps, minimum of two per nostril, with a minimum nasal polyp score of 5/8. Following treatment with placebo and dupilumab secretion samples were collected from all patients and controls at regular intervals. Polyp biopsies were collected from only 14 patients. Both were analysed for total IgE, eotaxin 3 and eosinophil cationic protein (ECP). Side-effects of dupilumab included nasopharyngitis, headache and irritation at site of injection.

Levels of IgE and eotaxin 3 were significantly lower in the treated group compared with placebo in nasal secretions. Both IgE and eotaxin levels were also significantly lower in polyp samples when compared with base line levels and with controls.

Authors concluded that dupilumab’s effects on local inflammatory mediators are consistent with the improvement in signs and symptoms in study subjects. The study findings appear to recommend dupilumab as a dual-effect treatment for uncontrolled CRSwNP based on symptoms, signs, and topical tissue and secretions analysis. However, the small number of histological samples and, as in any monoclonal antibody, the cost and the side-effects need to be carefully weighted before such treatment is recommended even in reluctant cases. 

Dupilumab reduces local type 2 pro‐inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis.
Jonstam K, Swanson BN, Mannent LP, et al.
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Hassan Mohammed

North East Deanery, Newcastle, UK.

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