Methods: 784 North American and European adults with ragweed-pollen induced allergic rhinoconjunctivitis were randomized 1:1:1:1 to receive daily ragweed AIT 1.5 Amb a 1-U, 6 Amb a 1-U, 12 Amb a 1-U, or placebo approximately 4 months prior to and throughout the ragweed pollen season. Rescue medications and symptoms were recorded in electronic diaries daily during ragweed season. Efficacy end points included the total combined daily symptom and medication score (TCS), symptom score (DSS), and medication score (DMS) during the entire season. Safety was monitored through adverse event (AE) reporting and by an external data and safety monitoring committee.
Results: Overall 99% of the subjects were multisensitized and 17% had concomitant asthma. The ragweed AIT 12 Amb a 1-U, 6 Amb a 1-U, and 1.5 Amb a 1-U groups showed between-treatment mean differences of 27% (p=0.0003), 18% (p=0.0125), and 12% (p=0.0878) improvement in TCS compared to the placebo group, respectively. The DSS for 12 Amb a 1-U improved significantly (21%, p=0.0021) and showed only numerical improvement for 6 Amb a 1-U (9%) and 1.5 Amb a 1-U (7%) doses. The DMS for 12 Amb a 1-U (38%, p=0.0026) and 6 Amb a 1-U (35%, p=0.0040), also improved significantly for the active groups. Treatment effects were similar in North Americans and Europeans, and the majority of treatment-related AEs were mild, local, application-site reactions with no reports of systemic allergic reactions.
Conclusions: This study confirms dose-dependent efficacy of the ragweed AIT. Overall, the comparison of efficacy among 3 doses of ragweed AIT showed the highest reductions in TCS, DSS, and DMS for the 12 Amb a 1-U tablet with 1.5 Amb a 1-U being ineffective. Although further studies are required, the tolerability, safety, and efficacy of the AIT may permit availability of a novel treatment option to a broader group of patients with ragweed pollen allergy.