Efficacy of dupilumab in patients with a history of prior sinus surgery for chronic rhinosinusitis with nasal polyps

Abstract

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease treated with sinus surgery when refractory to medical intervention. However, recurrence postsurgery is common. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor for interleukin 4 (IL-4) and IL-13, key and central drivers of type 2 inflammation. We report the efficacy of dupilumab in patients with CRSwNP from the SINUS-24/SINUS-52 trials (NCT02912468/NCT02898454), by number of prior surgeries and time since last surgery.

Methods: Patients were randomized to placebo or dupilumab 300 mg every 2 weeks. Post hoc subgroup analyses were performed for patients with 0, ≥1, 1/2, or ≥3 prior surgeries, and for patients who had surgery within <3, 3 to <5, 5 to <10, or ≥10 years. Efficacy outcomes at 24 weeks included co-primary endpoints nasal polyp score (NPS) and nasal congestion (NC), and Lund-Mackay (LMK), 22-item Sino-Nasal Outcome Test (SNOT-22), and smell scores.

Results: Of 724 patients randomized, 459 (63.4%) had ≥1 prior surgery. Baseline sinus disease (NPS, NC, LMK) and olfactory dysfunction (University of Pennsylvania Smell Identification Test [UPSIT] and loss of smell) scores were worse for patients with ≥3 prior surgeries vs no surgery. Baseline NPS and LMK were worse in patients with <3 years since last surgery than in patients with ≥5 years since last surgery. Dupilumab significantly improved all outcome measures vs placebo in all subgroups by number of surgeries and by time since last surgery. Improvements in NPS and LMK were greater in patients with <3 years since last surgery than patients with ≥5 years. Safety results were consistent with the known dupilumab safety profile.

Conclusion: Dupilumab improved CRSwNP outcomes irrespective of surgery history, with greater improvements in endoscopic outcomes in patients with shorter duration since last surgery.

Keywords: chronic disease; chronic rhinosinusitis; sinus surgery; subcutaneous immunotherapy; therapeutics.

FIGURE 1

Dupilumab efficacy outcomes at week 24 by number of prior sinus surgeries, and by time since last sinus surgery. All panels show the LS mean difference in change from baseline, comparing the dupilumab vs placebo. ^*Subgroup‐by‐treatment interaction p < 0.05; ^** p < 0.01; ^*** p < 0.001. LS mean: imputed complete data were analyzed by fitting an ANCOVA model with the corresponding baseline value, treatment group, asthma/NSAID‐ERD status, regions, and the study as covariates. Analysis was based on the same imputed dataset using WOCF/MI from primary analysis of the co‐primary endpoints. Interaction p value computed by fitting an ANCOVA model with the corresponding baseline value, treatment group, asthma/NSAID‐ERD status, and regions as covariates, plus the subgroup variable and the subgroup‐by‐treatment interaction and the study. The “no surgery” and <3 years subgroups were considered as references for the calculation of the interaction p values for the number of surgery and the time since most recent surgery subgroup analyses, respectively. ANCOVA = analysis of covariance; CI = confidence interval; LS mean = least squares mean; NSAID‐ERD = nonsteroidal anti‐inflammatory drug‐exacerbated respiratory tract disease; SNOT‐22 = 22‐item Sino‐Nasal Outcome Test; SE = standard error; UPSIT = University of Pennsylvania Smell Identification Test; WOCF/MI = worst observation carried forward/multiple imputation.

FIGURE 2

Differences in the proportion of patients achieving treatment response thresholds at week 24 by number of prior sinus surgeries, and by time since last sinus surgery. All panels show risk differences for response outcomes, comparing the dupilumab vs placebo groups. ^*Treatment‐by‐subgroup heterogeneity p < 0.05. RD derived in each subgroup using logistic regression with treatment group, asthma/NSAID‐ERD status, prior surgery history, regions, and the study; interaction p values derived using the same model, with the additional inclusion of the subgroup, and the subgroup‐by‐treatment interaction as covariates. The “no surgery” and <3 years subgroups were considered as references for the calculation of the heterogeneity p values for the number of surgery and the time since most recent surgery subgroup analyses, respectively. CI = confidence interval; NSAID‐ERD = nonsteroidal anti‐inflammatory drug‐exacerbated respiratory tract disease; RD = risk difference; SNOT‐22 = 22‐item Sino‐Nasal Outcome Test.