Novel Systematic Review Ideas for Biologics in Chronic Rhinosinusitis
Based on the current evidence landscape, here are high-yield systematic review topics that would meaningfully advance the field:
Head-to-Head Comparative Effectiveness Reviews
Dupilumab versus omalizumab versus mepolizumab in CRSwNP - While individual placebo-controlled trials exist for all three biologics 1, only one head-to-head trial (EVEREST) has directly compared dupilumab to omalizumab 2. A comprehensive network meta-analysis incorporating all available direct and indirect comparisons would clarify relative efficacy across multiple outcomes including quality of life, polyp reduction, and smell restoration 1, 2.
Cost-effectiveness analysis across biologics - Current literature questions the cost utility of biologics compared to surgery and other interventions 3. A systematic review with economic modeling comparing dupilumab, omalizumab, and mepolizumab against surgical intervention and each other would address a critical knowledge gap for healthcare systems and payers 3.
Phenotype-Specific Treatment Response
Biologics in CRSwNP patients stratified by endotype - While dupilumab targets IL-4/IL-13 signaling, omalizumab targets IgE, and mepolizumab targets IL-5 1. A systematic review examining treatment responses based on baseline inflammatory markers (eosinophil counts, IgE levels, IL-5 levels) would guide precision medicine approaches 1.
Biologics in CRS without nasal polyps (CRSsNP) - Current evidence overwhelmingly focuses on CRSwNP patients (99.8% of participants in available trials) 4. A systematic review specifically examining the limited evidence for biologics in CRSsNP would identify this critical research gap and inform future trial design 4.
Long-Term Outcomes and Durability
Long-term efficacy beyond 52 weeks - Most trials evaluate outcomes at 16-52 weeks 1. A systematic review examining durability of response, relapse rates after discontinuation, and optimal treatment duration would address real-world clinical questions about maintenance therapy 1, 5.
Surgery avoidance and revision surgery rates - While biologics may reduce need for surgery 4, a systematic review quantifying surgical avoidance rates, time to surgery, and revision surgery rates in biologic-treated versus conventionally-managed patients would demonstrate long-term clinical value 4, 3.
Comorbidity-Focused Reviews
Biologics in CRSwNP with comorbid asthma - Between 43-100% of trial participants had asthma 1, 4. A systematic review examining dual respiratory benefits, including FEV1 improvements and asthma control questionnaire scores, would clarify which biologic provides optimal management for this common comorbidity pattern 1, 2.
Biologics in aspirin-exacerbated respiratory disease (AERD) - This severe phenotype often includes CRSwNP, asthma, and aspirin sensitivity. A focused systematic review on biologic efficacy in AERD would address management of this particularly refractory population 6.
Safety and Adverse Event Profiles
Comparative safety analysis across biologics - While dupilumab may cause conjunctivitis, and other biologics have different adverse event profiles 1, a comprehensive systematic review of safety data including injection site reactions, systemic effects, and long-term safety signals would inform risk-benefit discussions 1, 5, 4.
Serious adverse events and treatment discontinuation rates - Current evidence shows variable serious adverse event rates (dupilumab 5.9%, mepolizumab 1.4%, omalizumab 0.8%) 1, 4. A systematic review examining reasons for discontinuation and predictors of adverse events would improve patient counseling 4.
Dosing and Administration Optimization
Optimal dosing regimens and de-escalation strategies - Studies have used different dosing schedules (every 2 weeks versus every 4 weeks) 1. A systematic review examining dose-response relationships and maintenance dosing strategies would optimize treatment protocols 1, 5.
Subcutaneous versus potential alternative delivery routes - All current biologics are subcutaneous 1, 5. A systematic review examining any emerging evidence for alternative administration routes or formulations would identify future research directions 5.
Predictive Biomarkers and Treatment Selection
Biomarkers predicting biologic response - A systematic review identifying baseline characteristics (eosinophil counts, IgE levels, polyp scores, CT scores) that predict treatment response would enable better patient selection and reduce treatment failures 1, 6.
Role of tissue eosinophilia versus blood eosinophilia - While blood eosinophils are commonly measured 1, a systematic review examining whether tissue eosinophilia better predicts biologic response would refine patient selection criteria 1, 6.
Combination and Sequential Therapy
Biologics combined with surgery timing - The optimal timing of biologics relative to endoscopic sinus surgery remains unclear 3. A systematic review examining pre-operative, peri-operative, and post-operative biologic use would establish evidence-based treatment algorithms 3.
Biologics with intranasal corticosteroids versus biologics alone - All major trials used background intranasal steroids 1, 4. A systematic review examining whether biologics provide additional benefit beyond intranasal steroids alone would clarify additive effects 1, 4.
Patient-Reported Outcomes and Quality of Life
Smell restoration across biologics - Anosmia significantly impacts quality of life 6. A systematic review comparing smell improvement (UPSIT scores) across biologics would identify which agent best addresses this debilitating symptom 1, 2.
SNOT-22 minimal clinically important differences - While the MCID is established at 8.9 points 1, 4, a systematic review examining whether different biologics achieve clinically meaningful improvements and how this correlates with other outcomes would validate treatment success 1, 2, 4.
Emerging Biologics and Novel Targets
Anti-IL-33, anti-TSLP, and other pipeline biologics - Beyond the three approved biologics 6, 4, a systematic review of emerging biologics targeting other type 2 inflammatory pathways would identify future treatment options 6.
Biologics targeting non-type 2 inflammation - Since not all CRS is type 2-driven 6, a systematic review examining biologics for non-type 2 endotypes would address treatment gaps for these patients 6.