By Will Boggs MD
NEW YORK (Reuters Health) - 27/9/2019
Dupilumab reduces polyp size and symptom severity in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), according to results from two randomized clinical trials.
Dr. Claus Bachert of Ghent University, in Belgium, told Reuters Health by email that this "innovative approach" offers "help for patients otherwise not treatable" and "may reduce the need for surgery."
Dupilumab is a monoclonal antibody that inhibits signaling by IL-4 and IL-13, key drivers of type 2 inflammation. It has been approved by the U.S. Food and Drug Administration (FDA) as an add-on maintenance treatment in adult patients with inadequately controlled CRSwNP.
Dr. Bachert and colleagues assessed the efficacy and safety of dupilumab when added to intranasal corticosteroids in adults with severe CRSwNP in two phase-3 trials, LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52.
In SINUS-24, researchers assigned 143 patients to dupilumab every two weeks and 133 patients to placebo; in SINUS-52, 150 patients received dupilumab every two weeks, 145 every two weeks until week 24 and every four weeks until week 52, and 153 patients received placebo.
At baseline, mean bilateral endoscopic nasal polyp score (NPS) was 5.97 (scale, 0-8) and mean nasal congestion or obstruction score was 2.40 (scale, 0-3) in the overall population. Changes in these measures were the co-primary endpoints in both studies.
Endoscopic NPS decreased by a mean 1.89 points in SINUS-24 and by a mean 1.71 points in SINUS-52 with dupilumab every two weeks, compared with slight increases with placebo (0.17 and 0.10 point, respectively), the team reports in The Lancet, online September 19.
Nasal congestion or obstruction scores also improved significantly in both studies (by a mean 1.34 and 1.25 points, respectively), compared with placebo (mean improvements of 0.45 and 0.38 points, respectively).
The magnitude of improvements was similar in patient subgroups with comorbid asthma, NSAID-exacerbated respiratory disease, or previous surgery.
Patients treated with dupilumab in SINUS-52 progressively improved up to week 52, whereas symptoms worsened after discontinuation of dupilumab at week 24 in patients in SINUS-24.
Dupilumab treatment was also associated with significant improvements in Lund-Mackay CT scores (a radiologic staging system for chronic rhinosinusitis), total symptom scores, smell test scores, and the 22-item Sino-Nasal Outcome Test (SNOT-22) scores, compared with placebo.
In the subset of patients with comorbid asthma, dupilumab treatment was associated with significantly improved FEV1 and asthma control.
In the pooled 24-week safety population, the rate of treatment-emergent adverse events did not differ significantly between placebo (74%) and dupilumab (69%) (95% confidence interval, -13.04 to 0.08).
"These data support the benefits of adding dupilumab to daily standard of care in patients with CRSwNP as a novel approach in treating the entire spectrum of clinical manifestations of the disease, a predominantly type 2 inflammatory condition, as well as the frequently associated type 2 lower airway comorbidities," the authors conclude.
Dr. Whitney W. Stevens from Northwestern University Feinberg School of Medicine, in Chicago, who wrote a linked editorial, told Reuters Health by email, "Patients with CRSwNP report significant impairments in their quality of life and more than half of these patients also have comorbid asthma. This is not trivial, as the presence of asthma is associated with more severe CRSwNP and vice versa. This study provides strong evidence for dupilumab as a treatment option for CRSwNP, and other studies support its efficacy in asthma."
"Clearly, patients with CRSwNP who have failed sinus surgery, have contraindications to surgery, and/or who have required frequent systemic corticosteroids to manage their disease would be candidates for dupilumab," she said. "Additionally, patients with both asthma and CRSwNP are appropriate candidates."
"Questions that remain unanswered at this time (and should be addressed by physicians) include how soon dupilumab should be considered in the management of CRSwNP patients (i.e., before the first sinus surgery?) and how the cost of the drug may impact its real-world use," Dr. Stevens said.
Dr. Robert Schleimer, chief of Allergy and Immunology at Feinberg School of Medicine, who was not involved in the study, told Reuters Health by email, "This paper confirms the results from the phase 2 study that preceded it. Dupilumab may find a market in patients with severe nasal polyps, either as an alternative to surgery or an adjunct to surgery."
Sanofi and Regeneron Pharmaceuticals sponsored the trials, employed several of the authors, and had various relationships with many others, including Dr. Bachert.
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