In a specialty clinic, dupilumab (Dupixent) injections significantly improved symptoms for patients with chronic rhinosinusitis with nasal polyps, based on provisional data from more than 100 adults.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a significant burden among working-age adults. Symptom control remains a challenge for many of these patients, and the cost in lost productivity and healthcare consumption can be substantial, write Rik J.L. van der Lans, MD, of the University of Amsterdam, the Netherlands, and colleagues.
Dupilumab, a biologic that targets components of the type 2 inflammatory pathway, represents a new option that has shown effectiveness in clinical trials for regulatory approval, they said.
A new observational study tests dupilumab in patients who met criteria for biological treatment proposed in a recent major systematic review. The findings were published this month in the journal Allergy.
In the study, the researchers identified 131 adults older than 18 years (mean age 51.7) with CRSwNP treated at a single tertiary care center. Participants received 300 mg of dupilumab subcutaneous injection every 2 weeks for at least 12 weeks.
The primary outcomes were scores on several measures including the SinoNasal Outcome Test-22 (SNOT-22, scale of 0-110), the bilateral Nasal Polyp Score (NPS, scale of 0-8), and the Sniffin' Sticks-12 identification test (SSIT-12, scale of 0-6 anosmia, 7-10 hyposmia, 11-12 normosmia).
The mean scores on all three outcomes improved significantly from baseline to both 24 weeks and 48 weeks. Scores on the SNOT-22 improved from 52.4 at baseline to 18.5 and 16.8 at weeks 24 and 48, respectively. NPS improved from 5.4 at baseline to 1.6 and 1.0, respectively. SSIT-12 scores improved from 3.6 at baseline to 7.3 and 8.3, respectively.
At baseline, 95.8% of the patients had uncontrolled chronic rhinosinusitis, but at 24 and 48 weeks, respectively, 24.3% and 6.2% were uncontrolled.
Approximately half of the patients experienced treatment-emergent adverse events, but these were "mild and decreased in occurrence and intensity throughout treatment," the researchers say.
For patients with a strong response, the researchers also tested an extension of the interval between doses to 4 weeks and 6 weeks, in a provisional indication of continued established control at these timepoints.
The study findings were limited by several factors, including the potential for selection bias, and data from only the first patient cohort, the researchers noted. However, the results were strengthened by the real-life context, standardized indications, and long-term follow up for almost a year, they said.
More research is needed on nonacademic patient cohorts, but the current data confirm the effectiveness of dupilumab as an add-on for difficult-to-treat CRSwNP, they concluded. The findings also validate the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) inclusion criteria for biologic treatment, they said.
The new study is important because of the need for verification of results from randomized controlled trials using real-world data, Van der Lans told Medscape Medical News.
"For example, differences in treatment efficacy might result from differing indication criteria, and the inclusion/exclusion criteria in the RCTs might have excluded patients one would encounter in daily practice," he said. "With our prospective observational cohort, we are seeking to verify efficacy, monitor pharmacovigilance, and evaluate and advance the indication criteria and positioning of biologicals registered for CRSwNP, such as dupilumab.
"These cross-sectional results suggest dupilumab is more effective in preventing possibly harmful escape treatments, such as oral corticosteroids and/or surgery, than reported by the registration trials.
"Additionally, it appears possible to maintain established CRS-control during response-dependent, stepwise, interdose interval prolongation of up to 6 weeks, which is officially an off-label dosing interval," he said. "This would greatly benefit patients' treatment burden and direct costs, he said. However, both findings require corroboration by anticipated longitudinal results in 2022, he noted.
The key message for clinicians in practice: "Biologicals like dupilumab are a potent and promising treatment for severe CRSwNP when conventional medical and surgical therapy fails," he emphasized.
Looking ahead, important research objectives include head-on comparison studies of the diverse biological agents, establishing biomarkers to guide preferential therapy, and evaluating the economics of biologics compared with conventional therapy, Van der Lans added. Such research is vital not only for improving patient-centered care but to sustain the use of biologicals in a health-economic perspective, he added.
One of the greatest criticisms of biologic therapy for CRSwNP is cost, particularly in a setting of ever-increasing healthcare costs. A recent review noted the average cost per year is greater than $30,000.
Real-life Study Verifies Effectiveness
"As the authors pointed out, this is a real-life, prospective observational cohort with a decently large size, evaluating the therapeutic efficacy of add-on dupilumab," said Seong H. Cho, MD, of the University of South Florida, Tampa, in an interview with Medscape Medical News.
"Dupilumab is the first FDA-approved biologic to treat severe chronic rhinosinusitis with nasal polyps based on two phase 3 clinical trials," said Cho, who was not involved with the study. "It has been more than 2 years since dupilumab was approved for severe CRSwNP by the FDA and EMA. This real-life, prospective, observational study with a decent size verified the efficacy of dupilumab as an add-on treatment when used with a proper indication such as EPOS2020 indication criteria.
"I am not surprised by the efficacy of dupilumab on severe CRSwNP, based on my clinical experience. My clinical observation is similar to the results of this study.
"This study verifies that dupilumab is highly efficacious in treating refractory and severe CRSwNP in a real-life setting by improving all subjective and objective clinical outcomes such as SNOT-22, NPS, and smell test score," he said. The study also confirms that a stepwise, interdose interval prolongation from every 2-4 weeks for CRSwNP patients with good response should be a consideration for clinical practice, he added.
The cost-effectiveness of dupilumab is the main barrier to more consistent use, Cho said. "There is no evidence that dupilumab can change the course of the disease, and we don't know how long patients need to be on this drug. Therefore, nasal polyps need to be refractory and severe enough to use dupilumab and other biologics," he explained.
Consequently, proper indication criteria, such as the EPOS2020 indication criteria for biologics, should be established before initiating dupilumab, Cho noted.
"Generally, endoscopic sinus surgery would be preferred in sinus-surgery naive CRSwNP patients, unless surgery is contraindicated or refused by patients because of cost-effectiveness rather than the superior efficacy," he said. "If surgery fails, then dupilumab can be considered. In addition, proper evaluation of nasal polyp severity would be important.
"One should establish an objective NPS by endoscopic exam before initiation of dupilumab. This baseline score would be an important marker to assess the efficacy of dupilumab in the course of treatment."
Monitoring of the NPS together with the patient's symptom improvement would be essential to implementing a stepwise, interdose interval prolongation to reduce the cost, he emphasized.
"The most crucial additional research is establishing suitable biomarkers for the response of dupilumab and other biologics," said Cho. "Overall, the performance of dupilumab seems to be good. But there are patients unresponsive to dupilumab, even more to other recently FDA-approved biologics for CRSwNP."
Blood eosinophils and exhaled nitric oxide can be a good biomarker for type 2 asthma, Cho added. "Still, there is no evidence that these biomarkers are decent for CRSwNP even though CRSwNP is mostly considered as type 2 disease. Therefore, it would be essential to find promising biomarkers for severe CRSwNP."
Van der Lans disclosed serving as a consultant for GlaxoSmithKline, and several co-authors disclosed relationships with companies including Sanofi and Novartis. The patient registry from which the study population was drawn is cofunded by Sanofi and Novartis. Cho has disclosed no relevant financial relationships.
Allergy. Published in February 2022 edition. Full text
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Image 1: University of Amsterdam
Image 2: University of South Florida
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Cite this: Clinical Data Affirms Dupilumab for Chronic Nasal Polyps - Medscape - Feb 09, 2022.