Experts Provide Overview of CRSwNP, Available Biologic Treatments

In a continuing education course presented at this year’s Asembia Specialty Pharmacy Summit held in Las Vegas, May 2-5, Katharine Rimes, PharmD, a clinical specialty pharmacist at AMITA health, and John Bosso, MD, a clinical professor in the division of rhinology at the Perelman School of Medicine at the University of Pennsylvania, outlined updates in management of chronic rhinosinusitis with nasal polyps (CRSwNP).

CRS on its own is defined as inflammation of the nose and paranasal sinuses, Bosso explained, and while the immune response among those with CRS without polyps is typically neutrophilic, for patients with CRSwNP in the United States, 85% have an immune response with an eosinophilic background.

Among those with CRSwNP, the most prominent symptom is loss of smell and the condition can be associated with allergies, asthma or fungal or bacterial infections, he continued. The condition is also more frequeny in men, although women tend to suffer more severe disease.

In addition, underlying the 2 phenotypes (CRSwNP, and CRS without NP), are different endotypes of the condition. “In other words, there are different types of inflammatory responses that people have,” Bosso said. In the United States, the majority of patients with CRSwNP (85%) will have a type 2 inflammatory milieu, which makes the condition much harder to treat.

“It's not that type 1 inflammation or type 3 inflammation is easier to treat, but [type 2] can be much more challenging because of the recurrence risk, and also the risk associated with more severe asthma,” Bosso added.

Aspirin Exacerbated Respiratory Disease (AERD) and eosinophilic CRSwNP tend to be diffuse forms of the condition and thus more difficult to control. “Those endotypes tend to be the ones that are more likely to end up needing a biologic,” he said.

When it comes to disease management, the 3 main goals include reducing polyp size, reducing symptoms and improving quality of life—which studies have shown is on par with that on congestive heart failure—and preventing recurrence.

In the past, oral steroids served as the main treatment for CRSwNP, but long-term treatment resulted in unacceptable side effects, Bosso said. Intranasal steroids also had limitations in treatment efficacy, while surgical interventions run the risk for recurrence down the road. Aspirin desensitization and antibiotics have also been introduced as treatment options for patients with certain forms of the disease.

Finding the balance between the 2 extremes of repeated surgeries and introduction to biologics without testing any preliminary steps is critical in effective disease management, Bosso said.

In the second half of the presentation, Rimes discussed the 3 currently available FDA-approved biologics for CRSwNP: dupilumab, omalizumab, and mepolizumab.

Omalizumab is indicated as add-on maintenance for treatment of CRSwNP in adults who had an inadequate response to internasal corticosteroids, Rimes explained, while dosing is based off the patient’s total serum IGE level and body weight. However, the dosing of this biologic in asthma is different than that for CRSwNP, underscoring the importance of a correct primary diagnosis. Prefilled syringes of omalizumab do contain natural rubber latex, so any patient with a latex allergy should be aware of this risk, she noted.

“For all of the biologics ,patients should be counseled to continue all other medications that they are using for the treatment of CRSwNP unless otherwise directed to stop by their provider,” Rimes said.

Mepolizumab is also indicated as an add-on maintenance treatment for adults with CRSwNP. As post marketing reports have shown hypersensitivity reactions occurring on a delayed basis on the day of administration, patients should notify providers of any signs or symptoms of hypersensitivity reactions. In the trials supporting the approval of mepolizumab, all patients had a history of internasal corticosteroids and of NP sinus surgery.

Dupilumab, again indicated as add-on maintenance therapy for adults with inadequately controlled CRSwNP, does not have a loading dose for treatment of this disease while it does for other indications including asthma, Rimes explained. Patients should also monitor for hypersensitivity reactions and immediately alert their provider should they occur. In the clinical trials supporting dupilumab’s approval, included patients needed to have a prior sinonasal surgery or prior treatment for NP, or were ineligible to receive corticosteroids 2 years before enrollment.

Several more biologics are also in the pipeline for this condition. “Current evidence supports the use of biologic therapy in NP that's characterized by patients having recurrent polyps despite the standard of care or sinus surgery, symptoms that are non-responsive to maintenance nasal corticosteroid treatment, and patients with comorbid asthma,” Rimes said.

Costs of biologic treatments vary greatly depending on a variety of factors including dosing schematics and payer restrictions. However, all 3 manufacturers offer a quick start or bridge program to initiate treatment while patients wait for a prior authorization or appeal paperwork. But these programs are limited to those with private insurance, while additional programs exist for those with Medicare or Medicaid or who are uninsured. These initiatives are also subject to income limits.

Overall, dupilumab, omalizumab, and mepolizumab “have all been shown to reduce NP size and improve nasal symptoms. Mepolizumab and dupilumab may also reduce the need for sinonasal surgery and use a systemic corticosteroids," Rimes concluded.