Contemporary management of CRSwNP with an anti–IL-5 biologic

Recurrence of nasal polyps despite standard-of-care (SoC) treatment is common in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). At a recent symposium organized by the Hong Kong College of Otorhinolaryngologists, three Ear, Nose & Throat (ENT) specialists, namely, Professor Alkis Psaltis of The Queen Elizabeth Hospital, Adelaide, Australia, Dr Andrew Wong of Tuen Mun Hospital (TMH) and Dr Thomas Ho of Queen Mary Hospital (QMH), Hong Kong, shared insights into contemporary management of CRSwNP with surgery and an anti–interleukin (IL)-5 biologic (eg, mepolizumab), and discussed how a one-stop joint-specialty clinic approach optimizes management.

“Deeper understanding of chron­ic rhinosinusitis [CRS] has led to evolution of treatment from a focus on simple phenotypic manifesta­tions [ie, polyps or no polyps] to individu­alized, integrated management pathways depending on the cause of disease and inflammation endotype [ie, type 2 vs non-type 2],” said Psaltis.

Surgery: More than ventilation
Initial SoC treatment of CRSwNP in­cludes nasal irrigations, intranasal cortico­steroids, oral antibiotics, short courses of oral corticosteroids (OCS), and nasal sur­gery. “Of note, surgery is not considered curative, but is rather a means to improve medical management,” said Psaltis. [Rhi­nology 2020;58:1-464; J Asthma Allergy 2021;14:873-882]

“The role of surgery in CRS treatment is not only to improve ventilation and drainage and reduce inflammatory bur­den, but also to facilitate access of topi­cally applied drugs and assist in endotyp­ing the disease process,” added Psaltis.

“During surgery, tissue samples from nasal polyps can be obtained for histo­pathological examination, which can re­veal the type of inflammation [type 2 vs non–type 2], predominant inflammatory cell type [eg, eosinophils, neutrophils], inflammation severity, and presence of metaplasia or ulceration,” added Psaltis.

Joint clinic: A one-stop approach
CRSwNP is characterized by type 2 in­flammation and often co-occurs with other type 2 inflammation–related conditions, in­cluding aspirin-exacerbated respiratory dis­ease (AERD), asthma, and atopic dermatitis. [Heliyon 2023;9:e19249; ERJ 2020;56:232]

“[As illustrated in cases 1 and 2,] man­agement of CRSwNP requires a multidisci­plinary team effort,” Wong and Ho empha­sized. (Figure)

TMH experience: Airway Combine Clinic
“Our monthly Airway Combine Clin­ic, which brings together ENT surgeons and respirologists, has been exclusively dedicated to obstructive sleep apnoea management for years,” said Wong. “In November 2023, we expanded our ser­vices to provide biologics [ie, mepolizum­ab and dupilumab] to eligible patients with CRSwNP.”

“In our clinic, we assess nasal polyp histology, conduct endoscopy, perform smell test [eg, top international biotech smell identification test (TIBSIT)], administer the Sino-nasal outcome test [SNOT]-22, mea­sure immunoglobulin E [IgE] and eosinophil levels through blood tests, and manage co­morbid asthma,” added Wong. “We coordi­nate biologic injections for eligible patients at the day ward and provide follow-up appoint­ments to assess treatment compliance and monitor any adverse events [AEs].”

The eligibility criteria for biologics include a history of nasal surgery or being unfit for surgery, along with ≥3 of the following crite­ria, which are consistent with cases 1 and 2 and the European Position Paper on Rhi­nosinusitis and Nasal Polyps and European Forum for Research and Education in Aller­gy and Airway diseases (EPOS/EUFOERA) 2023 Guidelines

• Evidence of type 2 inflammation (ie, tissue eosinophils ≥10/hpf, blood eo­sinophil count (BEC) ≥150 cells/μL, or total IgE ≥100 IU/mL);
• Need for ≥2 courses of OCS per year, long-term low-dose OCS, or contra­indication to OCS;
• Significantly impaired quality of life (SNOT-22 ≥40);
• Significant loss of smell (anosmic on the smell test); and
• Diagnosis of comorbid asthma requir­ing regular inhaled corticosteroids. [Rhinology 2023;61:194-202] 

To date, 10 patients with CRSwNP (median age, 54 years; female, 60 per­cent) have been treated with mepolizum­ab or dupilumab (n=5 for each) at TMH’s Airway Combine Clinic. Common type 2 comorbidities in the cohort include asth­ma (90 percent), eczema (20 percent), and AERD (40 percent).

QMH experience: ENT-Allergy Joint Clinic
“A similar one-stop approach com­bining expertise in comprehensive diag­nosis and treatment has been adopted at QMH,” said Ho. “The ENT and Allergy & Immunology Joint Clinic carries out nasal endoscopy, smell tests, aeroallergen skin prick tests, serum IgE screening, biologic screening and counselling, and initiation of sublingual immunotherapy.”

At the ENT-Allergy Joint Clinic, six pa­tients have been started on mepolizumab for treatment of CRSwNP. “Most patients in our cohort achieved good response to mepolizumab in terms of nasal polyp score, nasal symptoms, and/or good asthmatic control,” reported Ho.

“Disease, patient, and treatment fac­tors constitute key elements of personal­ized management,” said Ho. As illustrat­ed in case 2, the presence of suspected AERD requires input from immunologists to optimize treatment.

Bridging trial data and local experience
Local experience, including cases 1 and 2, was generally consistent with find­ings of the phase III SYNAPSE trial, which included 407 patients with CRSwNP who were eligible for repeat nasal surgery de­spite SoC treatment and had ≥1 nasal surgery in the past 10 years. Patients were assigned to receive mepolizumab 100 mg subcutaneously or placebo Q4W, in addition to SoC. [Lancet Respir Med 2021;9:1141-1153]

“Results showed that adding mepo­lizumab to SoC significantly reduced en­doscopic nasal polyp score at week 52 [adjusted difference in medians, -0.73; 95 percent confidence interval [CI] -1.11 to -0.34; p<0.0001] and nasal obstruction visual analogue score [VAS] in weeks 49– 52 [adjusted difference in medians, -3.14; 95 percent CI, -4.09 to -2.18; p<0.0001] vs placebo,” reported Psaltis.

Additionally, mepolizumab-treated patients had significantly improved na­sal symptoms, including SNOT-22 total score at week 52 (adjusted difference in medians, -16.49; 95 percent CI, -23.57 to -9.42; p=0.0032) and loss of smell VAS symptom score during weeks 49–52 (adjusted difference in medians, -0.37; 95 percent CI, -0.65 to -0.08; p=0.020) vs placebo.