Real‐World Adverse Events After Type 2 Biologic use in Chronic Rhinosinusitis with Nasal Polyps

BackgroundThe indications for endoscopic modified Lothrop procedure (Draf 3) in patients with refractory chronic rhinosinusitis with nasal polyposis (CRSwNP) remain unclear. This study evaluates the effectiveness of Draf 3 for refractory CRSwNP focusing on improvements in disease severity and need for subsequent dupilumab rescue therapy.MethodsRetrospective review of patients with CRSwNP undergoing Draf 3 surgery at a tertiary center between 2012 and 2022. Clinicodemographic variables were compared across those who did versus did not require rescue with postoperative dupilumab. Time to postoperative dupilumab rescue was analyzed and longitudinal disease‐specific outcomes were measured using the sinonasal outcomes test (SNOT‐22).ResultsWithin 87 patients with CRSwNP, 24.1% had aspirin‐exacerbated respiratory disease (AERD). Significant improvement in SNOT‐22 score was found in CRSwNP with AERD (p < 0.001) and without AERD (p = 0.01) up to 24 months postoperative. 14.9% eventually required rescue with a dupilumab. More specifically, of 21 patients with AERD, 24.1% eventually required rescue with dupilumab. Dupilumab rescue was associated with a greater number of prior sinus surgeries (p = 0.02), prior aspirin desensitization (p = 0.02), and worse preoperative Lund‐MacKay scores (p < 0.001). No association between biologic rescue and frontal recess antero‐posterior diameter was found (p = 0.20).ConclusionsDraf 3 surgery in CRSwNP was associated with significant improvement in SNOT‐22 score at 24 months. Furthermore, only 14.9% of patients required dupilumab rescue. Patients with AERD were more likely to require rescue with dupilumab even though 75.1% avoided treatment with the biologic over the study period.

Rate of dupilumab use and symptom severity of patients with chronic rhinosinusitis with nasal polyposis after Draf 3 frontal sinusotomy

Ji,

Kellerman,

Mace

et al. 2024

Rheumatic adverse events associated with biologic therapy for chronic rhinosinusitis: A systematic review and meta‐analysis

Xiao,

Hsiao,

Khalil

et al. 2024

BackgroundBiologic therapies approved for treating chronic rhinosinusitis with nasal polyps (CRSwNP) have well‐established safety profiles but reports of rheumatic adverse events (AEs) are increasing and not well defined. This review aims to assess the risk and incidence of rheumatic AEs associated with biologic therapy in CRSwNP and summarize current reported management strategies.MethodsA protocol was registered in PROSPERO [CRD42024525663]. A search was conducted in four electronic databases: Medline (Ovid), Embase, Scopus, and Cochrane CENTRAL from inception until January 4, 2024. Two reviewers independently screened citations and extracted data. Methodological quality was assessed using the Joanna Briggs Institute's critical appraisal tool. Data were pooled using a random effects model to calculate overall incidence and relative risk.ResultsTwenty‐one studies met the final inclusion criteria, totaling 3434 patients of which 2763 (80%) received either dupilumab (n = 2257; 82%), mepolizumab (n = 372; 13%), or omalizumab (n = 134; 5%) for treatment of CRSwNP. The overall incidence rate for any on‐treatment rheumatic AE was 0.05 per person–year (95% CI, 0.03–0.09, I2 = 75%). Biologic therapy increased the risk of developing a rheumatic AE (RR = 2.53; 95% CI, 1.29–4.94) compared with placebo. The most frequently reported rheumatic AE was arthralgia or joint pain (n = 94; 95%), followed by lupus‐like syndrome or lupus erythematosus‐like reaction (n = 2; 2.5%). Discontinuation of treatment was the most common intervention (n = 21, 39%).ConclusionBiologic therapy increases the risk of rheumatic AEs in CRSwNP patients by over twofold. Healthcare providers should remain vigilant in monitoring rheumatic AEs and apply appropriate management strategies on a case‐by‐case basis.

Switching biologics in chronic rhinosinusitis with nasal polyps: A multicenter Canadian experience

Dorling,

Sarafan,

Voizard

et al. 2024

BackgroundType 2 biologics have been used increasingly for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). However, patterns of biologic switching are understudied, and established guidelines for sequential or simultaneous use do not yet exist.MethodsThis is a Canadian multicenter retrospective study of real‐world patient data. Patients were included if they had recurrent CRSwNP despite maximal medical and surgical management, and received at least one dose of a type 2 biologic. Patients who remained on their initial biologic comprised the continuous group. Patients with sequential or simultaneous use of more than one biologic comprised the switched group. We compared the characteristics of patients who continued and switched biologics.ResultsNote that 225 consecutive patients were included. Thirty‐six (16%) switched biologics at least once, and six (3%) switched twice. The most common switch was from mepolizumab to dupilumab, with poor control of CRSwNP symptoms being the leading cause for this switch. Lack of efficacy was the main reason for switching off mepolizumab and omalizumab, while adverse events were the leading cause for switching off dupilumab. Additionally, mepolizumab patients were more likely to switch biologics late in their treatment, while dupilumab patients rarely switched after 12 months of therapy (p‐value < 0.001).ConclusionsSwitching biologics for CRSwNP is frequent in Canadian rhinology practices, with 16% of patients switching at least once. The most common switch is from mepolizumab to dupilumab with inadequate CRSwNP control driving this switch. This study may help guide sequential or simultaneous use of biologics in CRSwNP patients.