The average Adjusted Symptom Score, a new primary efficacy end-point for specific allergen immunotherapy trials

Area of Science:

• Allergy and Immunology
• Clinical Trial Methodology
• Pharmacovigilance

Background:

• Current immunotherapy trials for allergic rhinoconjunctivitis use the average Rhinoconjunctivitis Total Symptom Score (ARTSS).
• Rescue medication use can mask treatment efficacy by reducing symptom scores, thus decreasing the difference between active and placebo groups.

Purpose of the Study:

• To introduce and describe the average Adjusted Symptom Score (AdSS).
• To provide a novel endpoint that integrates symptom severity and rescue medication use in allergic rhinoconjunctivitis clinical trials.

Main Methods:

• The AdSS adjusts the Rhinoconjunctivitis Total Symptom Score (RTSS) by incorporating rescue medication use.
• Daily AdSS values are determined by the higher of the current RTSS or the previous day's AdSS.
• The average AdSS was calculated retrospectively in trials of five-grass pollen sublingual immunotherapy and compared to ARTSS and other measures.

Main Results:

• The average AdSS effectively differentiated between active treatments and placebo.
• The AdSS confirmed findings from the ARTSS, demonstrating its validity.
• Adjusting for rescue medication use reduced the apparent placebo effect, offering a clearer view of treatment efficacy.

Conclusions:

• The average AdSS offers a valuable alternative primary efficacy endpoint for grass pollen allergic rhinoconjunctivitis trials.
• By accounting for rescue medication, the AdSS provides a more precise estimation of symptom severity and treatment effect.
• Prospective validation in large clinical trials is currently underway.