Dupilumab, benralizumab improve smell in chronic rhinosinusitis with nasal polyps
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Dupilumab and benralizumab both improved sense of smell in patients with chronic rhinosinusitis with nasal polyps, and benralizumab also decreased nasal blockage, according to results of two studies.
Dupilumab and CRSwNP
IL-4, IL-5 and IL-13 cytokines characterize the type 2 inflammatory signature found in most patients with CRSwNP in Western countries. Also, eosinophils, basophils and mast cells infiltrate nasal polyps, leading to a substantial impact on smell.
In fact, researchers described loss of smell one of the most troublesome and difficult-to-treat symptoms of CRSwNP, adding that it correlates with disease severity, has a substantial effect on quality of life and may be the first indicator of disease recurrence.
“The symptom burden of CRSwNP is very high. The decrease or absence of smell is a common symptom in CRSwNP patients,” study author Joseph K. Han, MD, chief of the division of rhinology and endoscopic sinus-skull base surgery and division of allergy at Eastern Virginia Medical School in Norfolk, told Healio.
Dupilumab (Dupixent; Sanofi Genzyme, Regeneron), a fully human monoclonal antibody, inhibits the signaling of IL-4 and IL-13. It already has been found to significantly reduce polyp size, sinus opacification and symptom severity for patients with CRSwNP, prompting the researchers to explore whether it improves loss as smell as well.
“Dupilumab targets IL-4 alpha, so we suspected it would improve patient symptoms including disturbance of smell,” said Han.
Han and colleagues evaluated pooled data from the SINUS-24 and SINUS-52 studies, which included 724 adults with severe CRSwNP (mean duration, 11 years; mean age, 51.4 years; 60.4% men), 63% of whom had prior sinonasal surgery, who were randomly assigned to receive placebo (n = 286) every 2 weeks for 24 weeks, or 300 mg subcutaneous dupilumab (n = 438) every 2 weeks for 52 weeks.
On a 0 to 3 scale with 0 being no symptoms and 3 being severe loss of smell, patients reported a mean baseline loss-of-smell score of 2.74 (standard deviation, 0.53).
The researchers also administered the University of Pennsylvania Smell Identification Test (UPSIT), where scores less than 19 on its 0 to 40 scale indicate anosmia. The 710 patients who took the UPSIT at baseline had a mean score of 14.
The patients in the dupilumab group reported rapid improvements in loss of smell, the researchers wrote, evident by day 3 (least-squares mean difference vs. placebo, 0.07; 95% CI, 0.12 to 0.02) and continuing progressively through 24 weeks (least-squares mean difference vs. placebo, 1.04; 95% CI, 1.17 to 0.91).
The patients assigned dupilumab also reported increases in UPSIT scores at each assessment (least-squares mean change at week 24, 10.54; difference vs. placebo, 10.57; 95% CI, 9.4-11.74).
Further, the researchers reported that the proportion of patients with anosmia in the dupilumab group dropped from 78% at baseline to 45% at week 2 and 28% at week 24. In the placebo group, the proportion of patients with anosmia did not change from baseline to week 24.
“We are so excited [dupilumab] improved the smell in the patients with CRSwNP,” Han said. “It was refreshing to see that patients were able to improve or have their smell return. What was surprising was how quickly they were able to get their smell back after dupilumab.”
Based on the rapidity and magnitude of the smell recovery they observed, the researchers wrote that type 2 inflammatory processes play a role in smell loss and that dupilumab treatment may reverse these processes.
“If patients with CRSwNP have lost their smell, dupilumab may be a good option to have their smell return,” Han said.
Benralizumab and CRSwNP
Based on the strong connection between CRSwNP associated with type 2 inflammation and tissue eosinophilia, eosinophils may play a mechanistic role in the disease’s pathogenesis, Claus Bachert, MD, PhD, of the Upper Airways Research Laboratory at Ghent University in Belgium, and colleagues wrote.
As a humanized, afucosylated monoclonal antibody, benralizumab (Fasenra, AstraZeneca) binds to cells that express the IL-5 receptor and targets them for enhanced antibody-dependent cellular cytotoxicity for rapid, near complete depletion of blood eosinophils and a reduction in basophil counts.
Researchers of the phase 3, randomized, double-blind, placebo-controlled OSTRO study enrolled 413 patients with severe CRSwNP who had been treated with intranasal or systemic corticosteroids and/or surgery for nasal polyps but remained symptomatic.
Researchers randomly assigned 207 patients (mean age, 50.1 years; 68.6% men) to receive benralizumab and 206 (mean age, 50.2 years; 59.6% men) to receive placebo, both in 30 mg doses every 4 weeks for the first three doses and every 8 weeks afterward.
Changes from baseline to week 40 in nasal polyp score (NPS) and patient-reported biweekly mean nasal blockage score (NBS) served as the study’s co-primary endpoints.
Compared with the placebo group, the benralizumab group reported significant improvements in their NPS (between-group difference, –0.57; 95% CI, 0.852-0.289) and NBS (between-group difference, –0.27; 95% CI, –0.458 to –0.083) scores at week 40, with improvements maintained through week 56.
However, there were no statistically significant improvements in Sinonasal Outcome Test-22 scores at week 40 (least-squares mean changes, –16.23 vs. –11.02), time to first nasal polyp surgery and/or systemic corticosteroid use for nasal polyps (HR = 0.75; 95% CI, 0.55-1.02), or time to first nasal polyp surgery (HR = 0.85; 95% CI, 0.53-1.36) between the groups.
The benralizumab group achieved nominally significant improvements in the difficulty in sense of smell score at week 40 (P = .003).
After subgroup analyses, the researchers found that comorbid asthma, number of nasal polyp surgeries, sex, BMI and baseline blood eosinophil count may have influenced treatment effects. They also said that benralizumab treatment was safe and patients tolerated it well.
For more information:
Joseph K. Han, MD, can be reached at hanjk@evms.edu.
References:
- Bachert C, et al. J Allergy Clinical Immunol. 2021;doi:10.1016/j.jaci.2021.08.030.
- Mullol J, et al. J Allergy Clin Immunol Pract. 2021;doi:10.1016/j.jaip.2021.09.037.