Mepolizumab effective for chronic rhinosinusitis with nasal polyps despite comorbidities
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Mepolizumab reduced polyp size and nasal obstructions in patients with chronic rhinosinusitis with nasal polyps regardless of comorbid asthma or aspirin-exacerbated respiratory disease, according to data from an exploratory analysis.
Researchers also observed a trend for greater clinical benefit among patients with higher baseline blood eosinophil counts, which they acknowledged may be a suitable biomarker for treatment.
Previously reported data from the SYNAPSE phase 3 randomized, double-blind, placebo-controlled parallel-group study showed that mepolizumab (Nucala, GlaxoSmithKline) — a monoclonal antibody that inhibits interleukin-5 — reduced nasal polyp (NP) size and nasal obstruction in patients with severe, bilateral CRSwNP who required revision surgery.
Claus Bachert, MD, PhD, head of the Upper Airways Research Laboratory at Ghent University Hospital in Ghent, Belgium, and colleagues conducted subgroup analyses of the study to stratify the efficacy of the drug based on the presence of comorbid asthma, comorbid aspirin-exacerbated respiratory disease (AERD) and baseline blood eosinophil count.
The analysis included 407 patients — 206 received 100 mg subcutaneous mepolizumab and 201 received placebo, both administered every 4 weeks for 52 weeks plus standard of care — 371 of whom had a blood eosinophil count of 150 cells/µL or greater (mepolizumab, n = 186; placebo, n = 185), and 278 with a blood eosinophil count of 300 cells/µL or greater (mepolizumab, 139; placebo, n = 139).
Overall, 289 patients had comorbid asthma (mepolizumab, n = 140; placebo, n = 149) and 108 had AERD (mepolizumab, n = 45; placebo, n = 63), with 103 of the patients with comorbid asthma also having AERD.
Results, published in The Journal of Allergy and Clinical Immunology, showed more patients in the intent-to-treat population assigned mepolizumab had a one point or greater improvement from baseline in their total endoscopic NP score at week 52 than those who received placebo (50.5% vs. 28.4%; P < .0001).
This benefit also was consistent among patients with comorbid asthma (52.9% vs. 29.5%) and comorbid AERD (51.1% vs. 20.6%), as well as among patients without these comorbidities.
Further, a greater proportion of patients assigned mepolizumab showed this improvement in total endoscopic NP score in the analysis according to blood eosinophil counts of 150 cells/µL or greater (49.5% vs. 28.1%) or 300 cells/µL or greater (50.4% vs. 28.1%).
Additionally, more patients showed a three point or greater improvement in their nasal obstruction visual analog scale score from baseline to weeks 49 through 52 with mepolizumab than with placebo (60.2% vs. 36.3%; P < .0001). Similar improvements occurred among patients with comorbid asthma (60% vs. 34.9%), comorbid AERD (64.4% vs. 30.2%), and blood eosinophil counts of 150 cells/µL or greater (59.1% vs. 34.1%) or 300 cells/µL or greater (59% vs. 32.4%).
Overall, patients who received mepolizumab had less risk for surgery than those who received placebo, with greater reductions in risk for patients without comorbid asthma and for patients with baseline blood eosinophil counts greater than the 150 cells/µL or 300 cells/µL cutoffs. Reductions in surgery risk were similar for patients with and without AERD.
Based on their analyses, the researchers concluded that 100 mg of subcutaneous mepolizumab administered every 4 weeks reduced NP size, nasal obstruction, risk for surgery and use of systemic corticosteroids, with a trend toward greater improvement in patients with higher baseline blood eosinophil counts. The treatment also improved nasal symptoms among patients with severe, bilateral CRSwNP regardless of whether they had asthma, AERD or both.
Perspective
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The results of this study are not surprising at all. In fact, they are similar to what we see in severe eosinophilic asthma (SEA) with mepolizumab. The treatment response is greatest in patients with eosinophil counts of 300 cells/µL and greater and in those with multiple associated comorbidities, such as CRSwNP. But like the asthma results, even those with blood eosinophil counts of 150 cells/µL to 300 cells/µL have some response to the drug.
Many of our severe asthma patients have comorbid CRSwNP, and we work closely with our ear, nose and throat sinus specialists to comanage these patients. Coexisting CRSwNP, especially when loss of smell occurs, has a huge negative impact on quality of life for our patients with asthma.
Surgical management of CRSwNP has evolved over the past 2 decades, but patients will tell you that these procedures are not for the faint of heart, especially when you have had more than one sinus surgery and still have sinus symptoms and get sinusitis frequently.
Mepolizumab therapy in this study not only decreased sinus symptoms, but treatment with mepolizumab also delayed or prevented the need for repeat sinus surgery in these patients who were identified as in need of another surgery. From a patient’s perspective, this is very significant.
These results also line up with our own experience in using mepolizumab and other biologics. In nearly all the pivotal phase 3 clinical trials for SEA, study participants with coexisting CRS with and without NP tended to be the most responsive to these drugs. There are no head-to-head comparisons to tell you which of these biologics — mepolizumab, benralizumab (Fasenra, AstraZeneca) or dupilumab (Dupixent; Regeneron, Sanofi) — would be the “best” for the nasal symptoms in a given patient, however.
Anecdotally, in the anti-IL-5 space, I have felt that mepolizumab impacts nasal symptoms in SEA with CRS more so than the others. In a patient presenting with prominent nasal symptoms, blood eosinophil counts greater than 150 cells/µL and SEA, I would likely start with mepolizumab as my first-choice biologic. In the anti-IL-4R space, dupilumab has shown good efficacy in moderate-to-severe allergic asthma and NPs and would also be a good first-line choice, especially for patients with coexisting allergies.
This study brings biologics into the otolaryngology space as a novel treatment outside surgery for patients with CRSwNP without the necessity of coexisting asthma or a referral to an asthma specialist. The results suggest a trial of mepolizumab treatment should be attempted for patients with elevated blood eosinophils prior to proceeding with surgery, and certainly on patients who have undergone surgery previously and failed.
To fully operationalize the use of mepolizumab in this space, it would be important to know dosing considerations. The currently licensed dose for asthma is 100 mg monthly. Could there be less frequent dosing for patient ease if it is for CRSwNP without asthma? We also would want to know how long it takes to see efficacy. If you start a patient on mepolizumab, how long should you wait before deciding to proceed with surgery anyway? Next, can the drug be stopped at some point? Because blood eosinophils do not totally correlate with efficacy, they are likely not the best surrogate biomarker to identify responders pre-therapy. What is needed is a better marker of tissue eosinophils in the nose. Could a better screening test be developed, such as a nasal brush?
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