Is it feasible to conduct a study on the effectiveness of biologic therapy for Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)?

Feasibility Assessment of Your Systematic Review Objectives

Yes, your proposed systematic review is highly feasible and addresses a critical gap explicitly identified by current guidelines—the lack of data on recurrence rates and predictors of response to biologics in CRSwNP. 1

Why This Study Is Needed and Feasible

Primary Objectives Are Directly Supported by Guideline Gaps

• The 2023 Joint Task Force guidelines explicitly call for "better tools to predict and quantify treatment response before starting biologics" as a top research priority. 1
• Your objective to estimate pooled recurrence/non-response rates directly addresses the fact that current RCTs focus on short-term efficacy (16-25 weeks) but lack long-term recurrence data. 2
• Comparing recurrence rates across different biologics (dupilumab, omalizumab, mepolizumab) fills a critical void since no head-to-head RCTs exist comparing these agents. 3
• Network meta-analyses have compared efficacy during active treatment 3, but your focus on recurrence after treatment cessation or during maintenance is novel and clinically essential.

Secondary Objectives Address Known Clinical Challenges

• Identifying predictors of recurrence is a recognized unmet need—current guidelines acknowledge that "not all patients respond equally" but lack biomarker-based algorithms for patient selection. 1, 4
• Recent evidence shows that low tissue eosinophils (<100 cells/HPF) and elevated serum neutrophils (≥5.75 × 10⁹ cells/L) predict poor biologic response 5, providing a foundation for your predictor analysis.
• Exploring heterogeneity by comorbid asthma/AERD, eosinophil levels, and prior endoscopic sinus surgery (ESS) is clinically relevant since guidelines recommend different biologics based on these factors (e.g., dupilumab for atopic dermatitis, mepolizumab for high eosinophilic burden). 6

Practical Considerations for Execution

Available Data Sources

• Multiple phase 2/3 RCTs exist for dupilumab, omalizumab, and mepolizumab 2, 3, though most report short-term outcomes (16-25 weeks).
• Real-world observational studies and registry data are emerging 7, which may provide longer follow-up data on recurrence.
• You will need to include both RCT extension studies and real-world cohort studies to capture recurrence data, as most RCTs end before recurrence becomes apparent.

Challenges You Will Face

• Heterogeneity in outcome definitions: Studies use different criteria for "recurrence" (e.g., return of nasal polyp score >X, need for rescue corticosteroids, need for surgery). You'll need to predefine acceptable definitions.
• Variable follow-up durations: Some studies may have 6-month data, others 12-24 months. Stratifying by follow-up duration (as you plan) is essential.
• Limited head-to-head data: Since no direct comparison RCTs exist 1, you'll rely on indirect comparisons, which have inherent limitations.
• Publication bias toward positive results: RCT extension studies may selectively report responders, underestimating true recurrence rates.

Specific Recommendations for Your Protocol

• Define "recurrence" clearly upfront: Consider using composite endpoints (e.g., nasal polyp score ≥X, SNOT-22 worsening by ≥8.9 points, need for rescue systemic corticosteroids, or surgery). 1
• Include both RCTs and real-world studies: RCTs provide internal validity but limited follow-up; real-world studies provide longer-term data but more confounding.
• Stratify by biologic class: Anti-IL-4Rα (dupilumab), anti-IgE (omalizumab), anti-IL-5 (mepolizumab), and anti-IL-5Rα (benralizumab) have different mechanisms and may have different recurrence patterns. 8, 4
• Plan subgroup analyses for:
  • Comorbid asthma (present vs. absent)
  • AERD (present vs. absent)
  • Baseline eosinophil levels (high vs. low)
  • Prior ESS (yes vs. no)
  • Tissue eosinophil levels (if reported) 5
  • Serum neutrophil levels (if reported) 5

Anticipated Findings Based on Current Evidence

• Dupilumab likely has the lowest recurrence rates given its superior efficacy on patient-important outcomes (SNOT-22, nasal symptoms, smell) during active treatment. 1, 3
• Patients with low tissue eosinophils and high serum neutrophils will likely have higher recurrence rates across all biologics. 5
• Comorbid asthma may predict better response since biologics are often dosed for asthma control, providing continuous treatment. 6
• Prior ESS may predict better outcomes since surgery reduces polyp burden before biologic initiation, though this is speculative.

Bottom Line

Your study is not only feasible but urgently needed. The 2023 guidelines explicitly identify lack of predictive tools and long-term outcome data as top research priorities. 1 You will face challenges with heterogeneous outcome definitions and limited long-term data, but these are surmountable with careful protocol design. Focus on clearly defining recurrence, including both RCTs and real-world studies, and stratifying by follow-up duration and patient subgroups. This work will directly inform clinical decision-making about which patients benefit most from which biologics and for how long treatment should continue.