Real-World Effectiveness of Polymerized House-Dust-Mite Subcutaneous Immunotherapy up to 24 Months: Why Baseline Symptom Severity Shapes Measurement of the Combined Symptom–Medication Response

Background/Objectives: Allergic rhinoconjunctivitis (AR) induced by house dust mites (HDMs) is a common condition that impairs quality of life, and allergen immunotherapy is the only treatment accepted to modify its natural course. However, real-world evidence on polymerized HDM subcutaneous immunotherapy (SCIT) remains limited. We evaluated the up to 24-month effectiveness of polymerized HDM SCIT and examined how baseline symptom burden affects the measured response. Methods: In a retrospective, single-arm, real-world cohort, 353 patients (mean age 15.9 (12.3) years) with HDM-induced AR with/without asthma (asthma subpopulation, n = 112) initiated polymerized SCIT (ALXOID®, Inmunotek S.L., Spain) with an extract of house dust mites (Dermatophagoides pteronyssinus, D. farinae, Blomia tropicalis). Patients were followed for up to 24 months; 139 contributed an observation at month 12 and 67 at month 24. The primary outcome was the Rhinoconjunctivitis Combined Symptom–Medication Score (RCSMS); secondary outcomes were a visual analog scale (VAS) and the ESPRINT-15 quality-of-life questionnaire. Effectiveness was estimated using mixed models for repeated measures. The pre-specified primary-analysis population was restricted to a baseline RCSMS ≥ 2 to avoid floor effects and regression to the mean at low baseline scores. Results: At month 24, the RCSMS decreased by 0.938 points (−35.3%) in the full cohort and by 48.3% in the baseline RCSMS ≥ 2 population; in the full cohort, the VAS and ESPRINT-15 improved by 50.6% and 69.7%, respectively (all p < 0.001; within-subject effect sizes were small for the full-cohort RCSMS and medium for all other outcomes). The shape of the improvement trajectory did not differ by age group, and all age groups exceeded the minimal clinically important difference; the age analysis was exploratory. Patients with baseline RCSMS < 2 showed continued improvement in VAS and ESPRINT-15 scores. In contrast, the RCSMS increased, a pattern consistent with a statistical floor effect, suggesting limited responsiveness of the score at low baseline values. Conclusions: Up to 24 months, polymerized HDM SCIT was associated with clinically meaningful improvements in symptoms, medication use, and quality of life, most clearly in patients with a baseline RCSMS ≥ 2. Baseline symptom severity should be considered when interpreting combined symptom–medication outcomes in allergen immunotherapy. The single-arm design precludes causal inference.