Tezepelumab in Adults with Severe Chronic Rhinosinusitis with Nasal Polyps.

Summary

In a 52-week, randomized, placebo-controlled trial in adults with severe, uncontrolled CRSwNP, tezepelumab significantly improved nasal polyp and congestion scores and reduced SNOT-22 and Lund-Mackay scores. Notably, indications for polyp surgery (HR 0.02) and systemic glucocorticoid use (HR 0.12) were dramatically reduced versus placebo.

Key Findings

• Tezepelumab improved total nasal-polyp score (mean difference −2.07; 95% CI −2.39 to −1.74) at week 52.
• Nasal congestion improved (mean difference −1.03; 95% CI −1.20 to −0.86) with P<0.001.
• Patient-reported outcomes improved: SNOT-22 (−27.26), loss-of-smell (−1.00), total symptom score (−6.89).
• CT extent decreased (Lund-Mackay −5.72).
• Marked reductions in polyp surgery indication (0.5% vs 22.1%; HR 0.02) and systemic glucocorticoid use (5.2% vs 18.3%; HR 0.12).

Clinical Implications

Tezepelumab provides a biologic option that can reduce surgical referrals and systemic steroid exposure in severe CRSwNP, complementing standard intranasal steroids and sinus care and potentially benefiting patients across T2-high and T2-low endotypes.

Limitations

• Industry-funded trial; generalizability beyond trial centers may vary.
• Adults only; long-term safety and durability beyond 52 weeks remain to be established.

Future Directions

Head-to-head comparisons with other biologics, biomarker-defined responder analyses (including T2-low), and real-world effectiveness/surgery avoidance studies are warranted.