Sinus Surgery Effectiveness Compared To Biological Therapies For Rhinosinusitis
Overview
This systematic review aims to compare the safety and efficacy of endoscopic sinus surgery (ESS) with various biologics in treating chronic rhinosinusitis with nasal polyps (CRSwNP) in adults by analyzing existing clinical trials. Five randomized controlled trials (RCTs) involving 1748 patients were included in the review, with outcomes measured through a random-effects model.
The results indicate that both ESS and biologics significantly improve key nasal outcomes in CRSwNP at both 6 months and 1 year. Dupilumab, a biologic, demonstrated superior efficacy over ESS in enhancing SNOT-22 scores at one year. However, ESS exhibited better performance than three biologics in improving nasal congestion scores (NCS) at two different time points, except for Dupilumab, which showed enhanced efficacy at 1 year. Regarding loss of smell scores, Dupilumab displayed greater improvement compared to other biologics and even ESS.
Safety analysis revealed no significant differences between the ESS cohort and biologic treatment. In summary, ESS demonstrated comparable improvements in quality of life and symptoms to Omalizumab, Mepolizumab, and Benralizumab. Dupilumab appeared more effective than ESS in specific aspects, highlighting the need for head-to-head trials and real-world studies to further compare their efficacy. The findings suggest that biologics can serve as alternative or adjuvant therapy for uncontrolled severe CRSwNP.
Introduction
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory condition affecting 2%-4% of the population, causing significant impairment of quality of life and economic burden. Current treatments involve medical therapies and endoscopic sinus surgery (ESS) for unresponsive cases. However, long-term recurrence after ESS necessitates novel therapies for sustained control. Recent research identifies a type 2 immune response in many Western CRSwNP patients, prompting exploration of biological therapies like Omalizumab, Mepolizumab, Dupilumab, Benralizumab, Tezepelumab, and Lebrikizumab.
This study aims to compare the efficacy and safety of these biologics with ESS through indirect treatment comparisons (ITCs), given the absence of direct head-to-head randomized controlled trials. While ESS, combined with medical therapy, has shown positive outcomes, the emergence of biological therapies presents a potential shift in the treatment landscape. The study seeks to guide treatment decisions for physicians and patients by evaluating the relative treatment effects on severe, inadequately controlled CRSwNP using data from existing RCTs.
Method
The systematic literature review aimed to assess randomized controlled trials (RCTs) comparing the efficacy and safety of endoscopic sinus surgery (ESS) versus biologics in the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). The search, conducted without language limitations, spanned from January 1, 1980, to April 30, 2022, using comprehensive search strategies. The primary outcome measure was the 22-item sinonasal outcome test (SNOT-22) score, a multi-domain questionnaire evaluating disease-specific health-related quality of life.
Data extraction and risk of bias assessment followed PRISMA recommendations, involving two investigators, with disagreements resolved by a third. Secondary outcomes included mean change from baseline at 6 months and 1 year in EQ-5D-5L vas score, loss of smell score, nasal obstruction score, peak nasal inspiratory flow (PNIF), exacerbation of CRSwNP requiring additional surgery, and serious adverse events (SAEs). Analysis of data requiring remedial surgery and SAEs occurred at the end of follow-up (EOF, longer than 48 weeks).
Statistical analysis involved meta-analysis, with Bucher indirect treatment comparison methodology used for each outcome. Pooled effects were generated through meta-analysis from results of the same biological treatment versus the control arm. The common comparator was intranasal corticosteroids (INCS), and the frequentist model was employed for conservative estimates, considering potential heterogeneity in RCTs.
Continuous outcomes were expressed as mean differences (MDs) or standardized mean differences (SMDs) with a 95% CI, while dichotomous outcomes utilized odds ratios (ORs) with 95% CI. A random-effects model measured pooled estimates of mean differences. The study aimed for quantitative analysis to provide insights into the comparative effectiveness of ESS and biologics in treating CRSwNP.
Inclusion Criteria
The study selected articles based on specific criteria: (1) Population: Adult patients (≥18 years old) seeking outpatient care for chronic rhinosinusitis with nasal polyps (CRSwNP) and experiencing ongoing symptoms such as nasal blockage, nasal discharge, facial pain/pressure, or loss of smell, regardless of prior treatment with standard steroids, nasal rinse, or surgery. (2) Study design: Randomized Controlled Trials (RCTs). (3) Intervention: Either endoscopic sinus surgery or various biologics for treating CRSwNP. This rigorous selection process ensures that the chosen articles contribute relevant and comparable data to the study’s objectives.
Exclusion Criteria
The inclusion criteria for this study involved (1) excluding patients with conditions that could potentially impact outcome results, such as active upper or lower respiratory tract infections, nasal cavity tumors, allergic fungal sinusitis, cystic fibrosis, and granulomatosis with polyangiitis. However, individuals with asthma were considered eligible for analysis. (2) Non-Randomized Controlled Trials (non-RCTs), meeting abstracts, review articles, case studies, case reports, as well as animal or in vitro studies were excluded. (3) Studies with fewer than 10 participants per treatment arm were not considered. (4) Endpoint evaluations conducted earlier than 48 weeks were also excluded. The rigorous selection process involved independent execution by two researchers, ensuring a comprehensive and unbiased approach, with any discrepancies resolved through mutual agreement.
Result
The systematic literature review analyzed five randomized controlled trials (RCTs) conducted from 2015 to 2020, comparing the efficacy of endoscopic sinus surgery (ESS) and four monoclonal antibodies (Dupilumab, Benralizumab, Mepolizumab, Omalizumab) in treating chronic rhinosinusitis with nasal polyps (CRSwNP). The trials included 1748 patients, with 118 undergoing ESS, 832 receiving monoclonal antibodies, and 798 on placebos, spanning 48 to 52 weeks.
The risk of bias assessment revealed that the included RCTs had a low risk of bias, except for attrition bias in three trials. SNOT-22 scores, a measure of health-related quality of life, demonstrated significant improvements in biological and surgical interventions, with Benralizumab showing delayed full benefit. ESS was equivalent to other biologics at 6 months but had similar efficacy to Dupilumab and Omalizumab at 1 year.
Symptom scores, including loss of smell and nasal congestion, favored ESS, Dupilumab, and Omalizumab. EQ-5D-5 L VAS score improvements were statistically significant for Dupilumab and Omalizumab at 6 months, but differences were minor compared to ESS. PNIF score improvements were seen with ESS at 6 months and 1 year, while Mepolizumab showed similar effects at 1 year.
The probability of needing remedial surgery favored ESS, Dupilumab, and Mepolizumab over placebo. Adverse events showed a similar incidence across biologics and ESS. A sensitivity analysis considering patients with a history of surgery supported the overall findings, with Dupilumab demonstrating better efficacy than Mepolizumab.
Conclusion
In addressing the persistent unmet treatment needs of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) post-endoscopic sinus surgery (ESS), the emergence of biologics targeting type 2 (T2) inflammation has significantly influenced treatment approaches. This study conducted a network analysis, utilizing data from recent randomized controlled trials (RCTs), to compare outcomes between patients undergoing biological and surgical interventions.
The meta-analysis faced challenges, such as inherent biases in indirect treatment comparison analysis and heterogeneity in inclusion criteria among RCTs. Despite these challenges, baseline features in the ESS group were found comparable to those in biologic therapy, supporting the feasibility of the analysis. Both biologics and ESS demonstrated favorable outcomes in improving symptoms and quality of life (QoL) measured by SNOT-22, EQ-5D, and VAS scores.
The study emphasized that, while ESS was effective, comparisons with biologics were limited by differences in scoring systems for nasal polyps. SNOT-22 improvements were generally comparable, but Dupilumab demonstrated superiority in certain key outcomes at specific time points. Biologics, particularly Dupilumab, showed better efficacy in improving nasal symptoms and QoL, albeit at a higher cost, challenging their cost-effectiveness compared to ESS.
Key findings included Dupilumab’s greater improvement in olfaction scores and extranasal rhinologic SNOT-22 subdomains compared to ESS. The study acknowledged limitations, such as the unavailability of subgroup data in the ESS cohort and the short follow-up period, emphasizing the need for long-term evaluations of biologics’ efficacy and safety.
In conclusion, the meta-analysis suggested that both ESS and biologics, especially Dupilumab, exhibited efficacy in improving symptoms and QoL in CRSwNP patients. The study recommended further head-to-head or real-world investigations to assess biologics’ application scenarios, considering factors like combination treatments and cost-effectiveness, in different endotypes of CRSwNP patients.
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