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HOST: Hello, and welcome! I’m your host, Sarah Pribis, and today I’ll be interviewing two experts to discuss their clinical approach to diagnosing and treating patients with chronic rhinosinusitis with nasal polyps, also called CRS with NP. Dr Nicole Chase is an immunologist and partner at St Paul Allergy & Asthma, as well as associate professor at the University of Minnesota School of Medicine. Dr Kibwei McKinney is a surgeon and otolaryngologist at SSM Health in Oklahoma City, Oklahoma. Thank you both so much for joining us.

DR CHASE: Thank you for having us.

DR MCKINNEY: Yes, it’s great to be here.

HOST: Let’s get started.

NARRATOR: INDICATION DUPIXENT is indicated as an add-on maintenance treatment in adult and pediatric patients aged 12 years and older with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP). CONTRAINDICATION: DUPIXENT is contraindicated in patients with known hypersensitivity to dupilumab or any of its excipients. Please see Important Safety Information throughout this video and the adjacent link for full Prescribing Information.

HOST: Dr Chase, could you get us started with a brief overview of the role of local and systemic inflammation in CRS with nasal polyps?

DR CHASE: Absolutely. CRS with NP is predominantly a disease driven by type 2 inflammation characterized by the presence of nasal polyps. More than 80% of patients with CRS with NP have evidence of underlying type 2 inflammation, so that’s a great place to start. Type 2 inflammation is driven in part by cytokines that promote local inflammation in the sinuses and nasal tissues. They also produce systemic markers of inflammation including elevated total IgE and peripheral blood eosinophil count. Physiological features associated with type 2 inflammation in CRS with NP include mucus hypersecretion and epithelial barrier dysfunction, while the associated clinical features range from impaired ability to smell to tissue remodeling, nasal polyp growth, and recurrence of polyps.

DR MCKINNEY: It is important to look for signs of type 2 inflammation when diagnosing a patient with CRS with NP. One sign I look for is the loss of sense of smell, which is highly indicative of type 2 inflammation. Patients may have a history of diseases driven in part by type 2 inflammation, such as asthma and allergic rhinitis. Consequently, they may have a history of steroid use and/or sinus surgery to manage their disease. Other patients may present with NSAID-exacerbated respiratory disease, with signs and symptoms that worsen with NSAID exposure. A final sign that polyps may be associated with type 2 inflammation may be the frequent nature of polyp recurrence.

DR CHASE: Exactly, Dr McKinney. This constant and chronic nature of type 2 inflammation-driven diseases such as CRS with NP means that I want to look for a treatment option that can help control not only the clinical manifestations of disease, but also address sources of the local and systemic inflammation.

DR CHASE: DUPIXENT® (dupilumab) Injection is an add-on treatment for inadequately controlled CRS with nasal polyps in patients 12 years and older that targets two of the key drivers of type 2 inflammation—IL-4 and IL-13 signaling.

HOST: That’s interesting, Dr Chase. How do these cytokines drive the manifestations of disease?

DR CHASE: The release of IL-4 and IL-13 contributes to a downstream inflammatory environment which is then associated with histologic changes and symptoms associated with type 2 inflammation, as discussed earlier. IL-4 signaling is a major driver of atopic disease because of its role in producing the allergic antibody IgE. IL-13 signaling leads to the mucus hypersecretion that is common in type 2 inflammation. It may also be implicated in the tissue remodeling involved in the development of nasal polyps. DUPIXENT targets these two major drivers of type 2 inflammation common to CRS with NP.

HOST: Thank you, Dr Chase. Dr McKinney, let's look at a sample patient with CRS with nasal polyps to see how DUPIXENT can work in clinical practice. Robert is a 56-year-old man diagnosed with CRS with NP 12 years ago. In the past 2 years, he has undergone nasal surgery and continued treating his symptoms with nasal irrigation as well as both inhaled and systemic steroids. As an ENT who might perform surgery on a patient like Robert, what can you tell us about his case?

DR MCKINNEY: I frequently see patients like Robert in my clinical practice. Despite being treated with standard-of-care therapies, he continues to struggle with burdensome symptoms, such as congestion and hyposmia. I evaluate these symptoms using nasal polyp scores, UPSIT scores, and patient-reported measures. Robert is likely caught in a recurring cycle of type 2 inflammation, which is not uncommon, even in patients who undergo surgery. In fact, 35% of surgical patients who have CRS with NP report postoperative recurrence of nasal polyps within 6 months. This rapid rate of recurrence post-surgery suggests to me that further surgeries may not be enough to provide relief. I advise clinicians to consider a treatment approach that can target the underlying type 2 inflammatory pathway.

HOST: Dr Chase, while Dr McKinney may be more likely to see patients seeking surgery, you may see patients who come to your practice complaining of allergies. What can you tell us about counseling such patients?

DR CHASE: Many patients who complain of “allergies” may actually endorse chronic rhinosinusitis symptoms, such as congestion or post-nasal drip. Asking about my patients’ sense of smell is one way to probe if nasal polyps may be present. I have noticed, though, that some patients get so used to their condition that they forget what it’s like to have the ability to smell. Often, it takes the temporary relief from a corticosteroid burst to remind them that improvement is possible. Unfortunately, we are increasingly aware of the risks associated with frequent oral corticosteroid use, which can include infection, hypertension, osteoporosis, and more.

HOST: Let's examine a sample patient case to see how this conversation might go in clinical practice. David is 41 and was diagnosed with CRS with NP 8 years ago. He is managing his symptoms with standard-of-care treatments but, unlike Robert, he has not had sinus surgery. He has a history of allergic rhinitis and continues to experience a reduced sense of smell. How would you approach a conversation with this patient?

DR CHASE: 74% of patients who have CRS with nasal polyps have comorbid allergic rhinitis, so providers should be prepared to recognize these as separate conditions. David’s loss of smell may be attributed to his nasal polyps. Like the vast majority of patients with CRS with nasal polyps, David's issue is uncontrolled. He is currently managing his recurring symptoms with intranasal and systemic steroids, but as his clinician, I would discuss alternative treatment options that address one of the underlying causes, reduce his dependence on oral steroids, and decrease his chance of requiring multiple surgeries.

DR MCKINNEY: Dr Chase, I’m so glad you mentioned the clinical goal of minimizing surgery for our patients with CRS with NP. Although ENTs may have received more training with surgical interventions, it is critical that we are aware of the full breadth of treatment options available to patients with this disease. I explain to patients that this is a systemic condition usually driven by inflammation, not simply a collection of polyps. While surgery may provide relief for some patients, they might also consider DUPIXENT, which can address an underlying source of type 2 inflammation.

HOST: Let’s talk about how exactly DUPIXENT can help the patients you see in practice. Dr Chase, how was DUPIXENT studied in clinical trials, and what do the coprimary endpoint data show?

DR CHASE: The efficacy of DUPIXENT in the treatment of CRS with nasal polyps was evaluated in two rigorous Phase 3 trials. SINUS-24 and SINUS-52 were placebo-controlled studies evaluating DUPIXENT with background intranasal corticosteroids over 24 weeks and 52 weeks, respectively. Treatment efficacy was evaluated across a range of both patient-reported and evaluator-assessed endpoints, including nasal congestion and nasal polyp scores, SNOT-22 score, UPSIT test score, and a patient’s own evaluation of loss of smell. The coprimary endpoints in both trials are shown on the screen, demonstrating reductions in both nasal congestion and nasal polyp scores for patients treated with DUPIXENT versus placebo at both 24 weeks and 52 weeks.

DR MCKINNEY: As I mentioned, I frequently see patients who have CRS with NP and continue to struggle with burdensome symptoms, like loss of smell. With DUPIXENT, patients reported a rapid improvement in sense of smell, with results seen as early as Day 3. In my clinical experience, early results like these have an important impact on the patient treatment journey. These patients may be used to the quick response of systemic steroids, so they may struggle to continue treatment with therapies with less rapid results. At Week 52, 72% of patients taking DUPIXENT had an UPSIT score above 18, compared to just 25% of patients taking placebo. A score at or below 18 indicates anosmia, which at least 74% of patients experienced at baseline, so this is a marked improvement. Indeed, many patients I treat with DUPIXENT have not been able to smell at all for years and now their smell has significantly improved. A final study parameter we’ll discuss is the use of rescue medications or treatments, which can indicate a patient’s disease remains uncontrolled. Rescue interventions were allowed in both study arms and less use of them indicates patients are getting their symptoms under control. Patients taking DUPIXENT saw a 74% reduction in systemic steroid use and an 83% reduction in the need for surgery vs placebo through Week 52. In a typical year before treatment with DUPIXENT, patients in my practice might receive multiple steroid bursts and even see their nasal polyps recur after surgery, so these are highly encouraging numbers.

HOST: They certainly are impressive. Dr McKinney, what should providers know about the safety profile of DUPIXENT?

DR MCKINNEY: The most common adverse reactions (incidence at least 1%) in adult patients with CRS with NP were injection site reactions, conjunctivitis, arthralgia, gastritis, insomnia, eosinophilia, and toothache. The safety profile of DUPIXENT through Week 52 was generally consistent with the safety profile observed at Week 24. This consistency is meaningful to patients, given that they are managing a chronic illness that they can expect to have to treat over the long term.

DR CHASE: DUPIXENT has no Boxed Warning and no known drug-drug interactions. In addition, DUPIXENT is not an immunosuppressant and requires no initial or ongoing lab monitoring, according to the Prescribing Information. It is unknown if DUPIXENT will influence the immune response against helminth infections. HOST: Thank you both so much for your time today. This has been an enlightening discussion. And thank you all for joining us. I hope you learned something that can benefit your clinical practice and the patients you treat. Please stay tuned for additional Important Safety Information.