Sublingual-oral administration of standardized allergenic extracts: phase 1 safety and dosing results.

BACKGROUND European studies provide a preponderance of evidence for sublingual allergen immunotherapy (SLIT) safety and efficacy, but they use allergen products that differ from those expected to be approved in the United States. OBJECTIVE To determine the safety and tolerability of 4 US-licensed standardized SLIT allergenic extracts. METHODS Adults 18 to 50 years old with allergic rhinitis with or without asthma due to timothy grass pollen, short ragweed pollen, house dust mite, or cat hair allergy completed a single-session dose escalation followed by an 8-week, open-label daily course of SLIT. Participants documented the presence and severity of adverse effects and adherence using a daily electronic diary. RESULTS Ninety-one participants initiated treatment, and 77 completed the phase 1 testing. Maximum tolerable doses ranged from 50 to 2,090 BAU for cat hair and dust mite extract, 31 to 91 Amb a 1 Units for short ragweed pollen extract, and 50 to 21,090 BAU for timothy grass pollen extract. During the 8-week treatment course, 98.9% of participants reported at least 1 mild, 70.4% at least 1 moderate, and 13.6% at least 1 severe adverse effect. Most adverse effects (94.6%) were rated as mild, 5.2% as moderate, and 0.1% as severe; nasal and oral-mucosal adverse effects were most commonly reported. No life-threatening adverse reactions occurred in more than 4,500 administered doses. CONCLUSIONS Daily sublingual-oral dosing of standardized allergenic extracts at maximum tolerable doses was generally well tolerated. These results are a first step toward establishing the safety of US-licensed SLIT extracts when appropriately self-administered and monitored.