The Minimal Clinically Important Difference in Allergen Immunotherapy: An Evidence-Based Approach

Area of Science:

• Allergy and Immunology
• Clinical Trials
• Patient-Reported Outcomes

Background:

• Regulatory bodies recommend symptom and medication scores for allergic rhinoconjunctivitis trials.
• Existing composite endpoint scales lack validation and a defined minimal clinically important difference (MCID).

Purpose of the Study:

• To determine the MCID for the EAACI-recommended Combined Symptom and Medication Score (CSMS0-6).
• To establish clinically meaningful thresholds for grass allergen immunotherapy (AIT) trials.

Main Methods:

• Collected patient feedback from 1071 grass-allergic individuals to define minimally relevant symptom improvement.
• Utilized the Rhinitis Quality of Life Questionnaire (RQLQ(S)) as an anchor, referencing data from registered sublingual immunotherapy (SLIT) products.
• Derived the MCID for CSMS0-6 using data from a Phase III trial (RESONATE) of PQ Grass 27,600 SU.

Main Results:

• 69% of patients found a 1-point symptom improvement satisfactory, translating to an MCID range of -0.23 to -0.21 for CSMS0-6 (-17% to -16%).
• A -0.34 point difference in RQLQ(S) was deemed clinically meaningful, based on SLIT grass tablet data.
• The RESONATE trial data anchored an MCID of -0.21 points (-16%) for CSMS0-6.

Conclusions:

• Patient feedback and RESONATE trial results support an average MCID of -0.22 points (-16%) for the CSMS0-6 scale.
• This provides essential minimal thresholds for concluding positive Phase III AIT trial outcomes compared to placebo.