Dupilumab shows ‘overwhelming’ response in treatment of nasal polyposis
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Dupilumab effectively treated nasal polyposis with minimal toxicity among treatment-refractory patients in a real-world setting, according to results of a retrospective cohort study published in Annals of Allergy, Asthma & Immunology.
Patients with nasal polyposis often experience chronic rhinosinusitis, a high symptom burden and poor quality of life, according to study background.
“Patients with nasal polyps typically have symptoms of nasal obstruction, sinus pressure and pain, copious nasal drainage, and loss of sense of smell and taste,” study researcher Jared I. Darveaux, MD, a specialist in allergy and immunology with Gundersen Health System, told Healio. “This can impact sleep and ability to concentrate at work, and can be socially embarrassing.”
Aspirin desensitization, recurring systemic corticosteroid use and sinus surgery are options for treatment-resistant disease, the researchers said.
“Patients with nasal polyps are often refractory to treatment with nasal steroids and, in my experience, the majority who have surgery eventually have polyp regrowth,” Darveaux said.
“Systemic steroids typically help temporarily but have multiple side effects so are not a good long-term treatment option,” he added. “Patients often want to try dupilumab in an effort to avoid repeat surgery or systemic steroids.”
As a human monoclonal antibody, dupilumab (Dupixent; Sanofi Genzyme, Regeneron) blocks the signaling of interleukin 4 and interleukin 13, which are cytokines that drive atopic dermatitis, asthma and nasal polyposis, among other allergic diseases. Dupilumab is an approved therapy for nasal polyposis.
“Previous randomized clinical trials have shown improvement in validated measures of symptom severity, improvements in sense of smell, reduced polyp size, reduced need for systemic steroids and repeat surgery, and improvement in endoscopic nasal polyp scores,” Darveaux said.
Researchers sought to evaluate the real-world efficacy and safety of dupilumab by searching Gundersen Health System’s medical records from Jan. 1, 2017, through Sept. 1, 2020, to identify patients who had been diagnosed with nasal polyposis and treated with dupilumab.
The analysis included 29 patients (mean age, 51.2 years; range, 24-73; 44.8% men) who received 300 mg dupilumab every 2 weeks for a median duration of 12 months (range, 0-20).
The researchers retrospectively graded each patient’s response to dupilumab according to the treating physician’s impressions during follow-up. They defined clinically meaningful response as a change in polyp size with treatment, based on CT imaging or rhinoscopy.
Mean follow-up was 11 months (range, 3-20).
Results showed 27 patients (93.1%) experienced improvements in their nasal polyps and related symptoms, such as congestion, anosmia, ageusia or hypogeusia.
Twenty-four patients (82.8%) experienced a complete response, three (10.3%) experienced a partial response and two (6.9%) had no response. Additionally, 28 patients (96.6%) experienced an objective response according to imaging or rhinoscopy, 24 (82.8%) had a complete response with no polyp noted and five (17.2%) presented with persistent polyps.
Four of the patients (80%) with persistent polyps experienced a decrease in polyp size but not complete resolution. Darveaux noted that even without complete resolution, patients still experienced improvements in symptom severity and some return of sense of smell.
Meanwhile, 10 out of 13 patients (76.9%) were able to discontinue systemic steroid use, which meant reduced risk for iatrogenic side effects from steroids such as osteoporosis, fractures, adrenal suppression, immune suppression, weight gain, poor glycemic control, glaucoma, cataracts, gastritis and psychiatric side effects, Darveaux said.
Further, 84.6% of patients who previously had a polypectomy saw their symptoms completely resolve with dupilumab, compared with 81.3% of those who did not have surgery.
Additionally, 92% of patients who had concomitant asthma saw their symptoms improve with dupilumab.
Dupilumab has limited adverse events compared with surgery and systemic steroid therapy, according to the researchers, who also noted the agent is well-tolerated with excellent response. After beginning use of the medication, none of the patients required surgery. The researchers also did not observe conjunctivitis or other injection site reactions, which have been reported in the literature.
However, one patient discontinued treatment due to a diffuse rash over more than 50% of his body surface, which was treated with triamcinolone injection and intranasal fluticasone.
“The rash that this patient experienced is an uncommon side effect with dupilumab treatment. It was unclear whether it was related to the medication, and I would not expect that this could be necessarily applied to a larger population,” Darveaux said.
In addition to the study’s small cohort size, retrospective design and observer bias, the researchers acknowledged they could not identify predictors of treatment response due to the “overwhelming response” in their cohort.
Additionally, the researchers warned that appropriate treatment duration has not been established. Because dupilumab is intended for preventive treatment, symptoms may recur once it is halted, researchers said.
Perspective
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The study by Nowsheen and colleagues reaffirms other clinical trials using dupilumab among patients with nasal polyposis. In fact, dupilumab received FDA approval for use in patients with chronic rhinosinusitis with nasal polyposis in 2019.
Nasal polyp disease with concomitant sinusitis is a very common condition for allergists and ENTs, as it is estimated that about one-third of patients with chronic sinusitis may have nasal polyps.
Historically, these nasal polyps have required surgical intervention to remove. But, unfortunately, the polyps will recur in as many as 50% of patients, leading to repeated surgeries. With the approval of dupilumab, and more recently omalizumab (Xolair; Genentech, Novartis) and mepolizumab (Nucala, GlaxoSmithKline), physicians have several effective biologic therapies to choose from in lieu of surgery.
This current study echoes the findings in other studies, in that dupilumab was effective in most of the patients and completely resolved the polyps in a number of patients with relatively few side effects.
This also mirrors what we are seeing in practice in that many patients with polyps — along with patients with asthma and eczema, which are the other indications for dupilumab — show very impressive improvement after starting the drug. Typically, this occurs within the first several months of treatment.
The hope for the future would be to have studies comparing the efficacy of the various biologics in the many approved diseases to determine which patients most benefit from which of the biologics.
Also, research into determining the best biomarkers to drive decision-making on which biologic would be best for the patient will be critical. This would lead to more individualized treatment for patients with allergic conditions and possibly improve efficacy while minimizing medication side effects.
Family Allergy & Asthma
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Nowsheen S and Darveaux JI. Ann Allergy Asthma Immunol. 2021;doi:10.1016/j.anal.2021.05.018.
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