Supplementary Material for: A Single-Center, Case-Control Study of Low-Dose-Induction Oral Immunotherapy with Cow's Milk

Background: This study aimed to investigate the efficacy and safety of low-dose-induction oral immunotherapy (OIT) with 3 ml of milk, which is a lower target volume than is conventionally used. Methods: Children aged ≥5 years with milk allergies [confirmed by oral food challenge (OFC) against 3 ml of milk] were enrolled. The OIT group was admitted to the hospital for 5 days for build-up. Subsequently, at home, the volume was gradually increased by up to a maximum of 3 ml every 5 days. While the OIT group ingested a small amount of milk every day, the control group completely eliminated their milk intake. Both groups underwent OFCs approximately 1 year later in order to assess their responsiveness to 3 ml and 25 ml of cow's milk. Results: The OIT and control groups had no background differences; the proportion of patients unresponsive to 3 ml of milk after 1 year was 58.3% (7/12) and 13.8% (4/25), respectively (p = 0.018), while the proportion unresponsive to 25 ml of milk was 33.3% (4/12) and 0.0% (0/25), respectively (p = 0.007). Furthermore, a significant decrease in the casein-specific immunoglobulin E levels was seen after 12 months when compared to baseline in the OIT group (p = 0.033). Adverse allergic reactions were rare and most symptoms were mild. Conclusion: This study of a high-risk population reacting to very low amounts of milk showed that low-dose-induction OIT appeared effective for acquiring unresponsiveness to 3 ml and 25 ml of milk, with severe symptoms being rare, indicating that for improvement of food allergies, continuous intake of small amounts may be as effective as intake of larger amounts.