[{"id":"itepe-asthma-loac","name":"Loss of asthma control (LOAC) events","type":"PRIMARY","unit":"odds ratio","results":[{"notes":"OR 0.42 (95% CI 0.20-0.88), p=0.02 vs placebo","value":22,"arm_id":"itepe-mono-asthma","arm_name":"Itepekimab mono"},{"notes":"OR 0.52 (95% CI 0.26-1.06), p=0.07 — NOT significant","value":27,"arm_id":"itepe-dupi-combo","arm_name":"Itepe + Dupi combo"},{"notes":"OR 0.33 (95% CI 0.15-0.70) — significant","value":19,"arm_id":"dupi-mono-asthma","arm_name":"Dupilumab mono"},{"value":41,"arm_id":"placebo-asthma","arm_name":"Placebo"}],"timepoint":"Week 12","description":"Proportion of patients experiencing loss of asthma control (≥30% decrease in FEV1, ≥50% increase in puffs/day, asthma exacerbation, or physician-assessed loss of control)."}]

Itepekimab monotherapy reduced LOAC by 58% (OR 0.42, p=0.02). Dupilumab monotherapy reduced LOAC by 67% (OR 0.33). KEY FINDING: The itepekimab + dupilumab COMBINATION was NOT superior to either monotherapy (OR 0.52, NS). This implies IL-33 and IL-4/IL-13 operate on the SAME pathway rather than being additive. Blocking upstream (IL-33) or downstream (IL-4Rα) achieves similar benefit; doing both adds nothing.

Phase 2 asthma (n=296, 12 weeks): Well-tolerated across all arms. No new safety signals.

The non-additivity of itepekimab + dupilumab is the key scientific insight. If IL-33 and IL-4/IL-13 were independent pathways, the combo should have been better. Instead, blocking IL-33 upstream achieves roughly the same effect as blocking IL-4Rα downstream. This argues against combined therapy and supports choosing one or the other.

Test whether IL-33 blockade adds benefit to IL-4Rα blockade (dupilumab) in moderate-to-severe asthma.