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Introduction and objectives Mepolizumab, an anti-interleukin-5 biologic, targets type 2 inflammation in CRSwNP. While the Phase III SYNAPSE trial demonstrated the efficacy of mepolizumab in reducing nasal symptoms and surgery needs by Week-52, the timing and progression of its clinical benefits remain less understood. This analysis evaluates response patterns to mepolizumab over time.Method SYNAPSE randomised patients 1:1 to receive subcutaneous mepolizumab 100 mg, or placebo, with standard of care. Response timings (weeks) for clinical outcomes were assessed post hoc by overall symptom visual analogue scale (overall VAS) and Sino-Nasal Outcome Test-22 (SNOT-22) responder status (defined as a ≥2.5-point and ≥8.9-point improvement from baseline, respectively) and nasal surgery status.Results Of the 407 randomised patients (206 mepolizumab, 201 placebo), mepolizumab demonstrated early efficacy in key clinical outcomes. During Weeks 9–12, a significantly higher proportion of patients in the mepolizumab group achieved clinically meaningful improvements in overall VAS scores, indicating reductions in nasal symptom burden ( table 1). Similarly, improvements in SNOT-22 scores were also observed by Week-4 and -12 in the mepolizumab group. By Week-36, mepolizumab reduced the risk of nasal surgery by 50% compared with placebo (table 1).Of those receiving mepolizumab, patients classified as overall VAS responders were significantly more likely than non-responders to subsequently be SNOT-22 responders. This association was observed as early as Week-12 (OR [95% CI]: 2.62 [1.10–6.24], p=0.030) and persisted through later time points, including Week-16 (OR [95% CI]: 3.09 [1.24–7.69], p=0.015) and Week-20 (OR [95% CI]: 2.44 [1.08–5.53], p=0.032). Furthermore, patients who achieved SNOT-22 responder status at Week-12 were significantly less likely to require nasal surgery by Week-20 (HR [95% CI]: 0.14 [0.03–0.70], p=0.016), with this association remaining statistically significant through Week-52 (p<0.02). Patients who had nasal surgery by Week-36 were more likely to require systemic corticosteroids prior to Week-36 than those who did not require nasal surgery (HR [95% CI]: 5.11 [2.38–10.96], p<0.001), with this continuing through Week-52.Abstract S160 Table 1Summary of improvements in overall symptom VAS, SNOT-22 and nasal surgery across time points in the SYNAPSE study Outcome Proportion of patients achieving overall symptom VAS responder status* (%) Proportion of patients achieving SNOT-22 responder status✝ (%) Proportion of patients requiring nasal surgery (%) N=206 (M); N=201 (P) Weeks 1– 4 (VAS);By Week 4 (SNOT-22, surgery) 6% (M) vs 7% (P)OR: 0.88(95% CI: 0.40–1.95) p=0.754 64% (M) vs 53% (P)OR: 1.66(95% CI: 1.09–2.53) p=0.017 N/A Weeks 9– 12 (VAS);By Week 12 (SNOT-22, surgery) 35% (M) vs 20% (P)OR: 2.20(95% CI: 1.39–3.47) p <0.001 82% (M) vs 64% (P)OR: 2.71(95% CI: 1.69–4.36) p <0.001 <1% (M) vs 2% (P)HR: 0.62(95% CI: 0.11–3.54) p=0.595 Weeks 33– 36 (VAS);By Week 36 (SNOT-22, surgery) 62% (M) vs 42% (P)OR: 2.22(95% CI: 1.49–3.32) p <0.001 75% (M) vs 61% (P)OR: 1.88(95% CI: 1.22–2.90) p=0.004 7% (M) vs 16% (P)HR: 0.50(95% CI: 0.26–0.95) p=0.033 Weeks 49– 50 (VAS);By Week 52 (SNOT-22, surgery) 64% (M) vs 40% (P)OR: 2.64(95% CI: 1.76–3.97) p <0.001 73% (M) vs 53% (P)OR: 2.44(95% CI: 1.60–3.73) p <0.001 9% (M) vs 23% (P)HR: 0.43(95% CI: 0.25–0.76) p=0.003 CI, confidence interval; HR, hazard ratio; M, mepolizumab; OR, odds ratio; P, placebo; SNOT-22, Sino-Nasal Outcome Test-22; VAS, visual analogue scale. *≥2.5 improvement; ✝≥8.9 improvement. Values are shown in bold where p<0.05.Conclusion Patients receiving mepolizumab achieve early responses with significant overall symptom VAS and SNOT-22 score improvements from Week-12, and nasal surgery benefits from Weeks 20–36, potentially predicting durable responses by Week-52.