Dupilumab improves taste in patients with chronic rhinosinusitis and nasal polyps

Dupilumab improved patient-reported taste compared with placebo among those with chronic rhinosinusitis with nasal polyps, according to study results presented during the European Academy of Allergy and Clinical Immunology Annual Meeting.

Anju Tripathi Peters, MD, director of clinical research in the division of allergy-immunology at Northwestern University Feinberg School of Medicine, and colleagues wrote these findings are consistent with the known central role of smell in taste.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2-mediated inflammatory disease associated with a high symptom burden, according to study background. Patients with the disease commonly report loss of taste in association with a loss of smell.

Between 55,000 and 90,000 adults in the U.S. have uncontrolled CRSwNP despite prior surgery or oral corticosteroid use, according to the researchers. In addition to loss of taste and smell, it can lead to nasal congestion, breathing difficulties, nasal discharge, and facial pain or pressure, as well as sleep disruptions and mood disturbances.

The current standard of care for restoring taste and smell among these patients includes intranasal and systemic corticosteroids and sinus surgery, both of which have significant recurrence rates of nasal polyps and symptoms.

Dupilumab (Dupixent; Sanofi Genzyme, Regeneron) — an inhibitor of IL-4 and IL-13 signaling, key and central drivers of type 2 inflammation, the underlying cause of the disease in 80% of patients — was the first biologic approved to treat uncontrolled CRSwNP in adults. It can help control persistent and often debilitating symptoms such as loss of smell and nasal obstruction, according to the researchers, in addition to reducing nasal polyp size and improving quality of life.

Because dupilumab improves smell among adults with uncontrolled CRSwNP and smell is related to taste, the researchers conducted an ad hoc analysis of data from the phase 3 SINUS-24 and SINUS-52 trials to assess the effect of dupilumab on patient-reported taste and its association with smell.

The researchers assessed patient-reported taste weekly among 650 patients (mean age, 51.32 years; 59.7% men) who were randomly assigned to 300 mg dupilumab every 2 weeks (n = 385) or placebo (n = 265). Patients rated their taste using a loss-of-taste severity scale of 0 to 3, with 0 being no loss; 1 being mild; 2 being moderate; and 3 being severe.

The researchers then analyzed scores in the intention-to-treat (ITT) and enriched populations to adjust for patients who had not reported any loss of taste.

Using Spearman’s rank correlation coefficient, the researchers also assessed associations between loss of taste severity and smell via the loss-of-smell score (LoS), University of Pennsylvania Smell Identification Test (UPSIT) and the 22-item Sino-Nasal Outcome Test (SNOT-22).

The researchers noted improvements in the severity of patient-reported loss of taste among patients treated with dupilumab compared to those treated with placebo in the ITT populations of both SINUS-24 and SINUS-52 at week 24. Specifically, the least-squares mean difference between the dupilumab and placebo group was –0.94 (95% CI, –1.14 to –0.74; P < .0001) for SINUS-24 and –0.77 (95% CI, –0.95 to –0.59; P < .0001) for SINUS-52 at week 24.

Researchers observed similar improvements in the enriched populations.

Further, the researchers found a higher proportion of patients assigned dupilumab compared with placebo achieved improvement in loss-of-taste severity at week 24 in the ITT population (61.2% vs. 26.2%) and in the enriched population (69.6% vs. 28.3%; both P < .0001), which persisted at week 52.

The researchers additionally observed moderate associations between improvement in loss-of-taste severity and improvements in LoS, UPSIT and SNOT-22 smell/taste item scores at week 24 in the ITT population (all P < .0001), with maintenance at week 52.

The trials demonstrated similar safety results to the known safety profile of dupilumab. The most common adverse events were injection site reactions; eye and eyelid inflammation, including redness, swelling, and itching; eosinophilia; insomnia; toothache; gastritis; and arthralgia.

Overall, these findings reinforce the benefit of addressing type 2 inflammation to improve burdensome sensory symptoms such as smell and taste, according to the researchers.