Real-World Use, Prescribing Patterns, and Short-Term Clinical Evolution of Extensively Hydrolyzed and Hydrolyzed Rice Formulas in Infants with Cow’s Milk Protein Allergy: An Analysis from the ETAPA Project

Background: Hydrolyzed rice formulas (HRFs) are increasingly recognized as an alternative nutritional option for infants with cow’s milk protein allergy (CMPA), but real-world data on prescribing patterns and early clinical evolution remain limited. Objective: This study aimed to describe real-world use and prescribing patterns of HRF and eHF in infants with CMPA, identify factors associated with HRF recommendation, and assess short-term clinical evolution after formula use. Methods: This observational analysis from the ETAPA project included two mutually exclusive infant-level cohorts: a prospective recommendation cohort assessing variables associated with HRF versus eHF recommendation, and a retrospective treated cohort assessing 7-day clinical evolution after formula use. In the retrospective cohort, the main clinical outcome was absolute change in CoMiSS from day 0 to day 7. A propensity score-weighted sensitivity analysis was performed to address measured confounding by indication. Results: Overall, 1505 valid infant-level records were analyzed: 1094 in the prospective cohort and 411 in the retrospective cohort. In the prospective cohort, HRF was recommended in 214/1094 records (19.6%). In multi-variable analysis, older infant age was associated with higher odds of HRF recommendation (OR 1.034 per month, 95% CI 1.002–1.067; p = 0.036), whereas IgE-mediated CMPA was associated with lower odds (OR 0.673, 95% CI 0.459–0.988; p = 0.043). In the retrospective cohort, CoMiSS decreased markedly in both groups (eHF: median reduction 7.0 [IQR 4.0–10.0] points; HRF: 6.5 [4.0–10.0] points; p = 0.661). After adjustment, HRF was not associated with a statistically significant difference in absolute CoMiSS reduction compared with eHF (β −0.513 points, 95% CI −1.108 to 0.082; p = 0.091). Conclusions: In routine pediatric practice, HRF was used across a broad range of CMPA profiles and was associated with clinically relevant short-term symptom improvement. These findings support HRF as an additional nutritional option for CMPA management, while the observational design precludes conclusions of equivalence or non-inferiority versus eHF.