D2.492 - Efficacy and safety of a 300IR daily dose of a SLIT of birch pollen allergen extract in children and adolescents with allergic rhinoconjunctivitis: results from the YOBI trial

Sublingual immunotherapy (SLIT) is a guideline-recommended treatment for allergic rhinoconjunctivitis (ARC), reducing symptoms and medication use. Although existing data suggests that early immunotherapy can be beneficial to prevent disease evolution, there is little evidence supporting SLIT efficacy in paediatric population. A large randomised, double-blind, placebo-controlled phase III trial (YOBI trial) conducted across Europe assessed the efficacy and safety of the 300IR birch pollen liquid sublingual immunotherapy (SLIT-liquid) in a paediatric population (5–17 years) with moderate-to-severe birch-induced ARC with/without controlled asthma over 2 birch pollen seasons (BPSs).

The intention-to-treat (ITT) set included all patients randomised (2:1) to receive daily 300IR birch SLIT-liquid or placebo over 2 consecutives BPSs (N=553). The primary endpoint was the average ARC total combined score (TCS_0-38), sum of average daily symptom score (DSS_0-18) and average daily medication score (DMS_0-20) during the second BPS (BPS2). A reduction of at least 2 points versus placebo on the TCS_0-38 (in symptom severity and/or rescue medication use) suggests clinically relevant improvements. Key secondary endpoints included the average Combined Symptom Medication Score (CSMS_0-6) at BPS2. An ANCOVA model was used for analysis.

Treatment with the 300IR birch SLIT-liquid resulted in a highly significant and clinically meaningful improvement of the primary endpoint. In the ITT, the least square (LS) mean difference in TCS_0-38 during BPS2 was -2.62 (95.5% CI: -3.64; -1.61; p < 0.0001), corresponding to a -41.74% relative difference vs. placebo (Figure). CSMS_0-6, DSS_0-18 and DMS_0-20 also showed a statistically significant improvement of 300IR vs placebo (Table).

During the first BPS (BPS1), the improvement in TCS_0-38 was already in favour of 300IR with a difference of -2.14 (99.5% CI: -3.55, -0.74; p < 0.0001), corresponding to a -34.30% relative difference. The favourable treatment effect was also supported by the other efficacy endpoints (Table).

Consistent with the established safety profile of 300IR birch SLIT-liquid, treatment-related adverse events were mild to moderate, and no new safety signals were identified.

300IR birch SLIT-liquid demonstrated a clinically relevant and highly statistically significant improvement of birch-induced ARC (with/without asthma) in paediatric population during BPS1 and BPS2, confirming a sustained effect, while showing a consistent safety profile.