Tolerance Induction in Cow's Milk Allergic Children by Heated Cow's Milk Protein: The iAGE Follow-Up Study.

Accelerating the induction of tolerance to cow's milk (CM) reduces the burden of cow's milk allergy (CMA). In this randomised controlled intervention study, we aimed to investigate the tolerance induction of a novel heated cow milk protein, the iAGE product, in 18 children with CMA (diagnosed by a paedriatric allergist). Children who tolerated the iAGE product were included. The treatment group (TG: n = 11; mean age 12.8 months, SD = 4.7) consumed the iAGE product daily with their own diet, and the control group (CG: n = 7; mean age 17.6 months, SD = 3.2) used an eHF without any milk consumption. In each group, 2 children had multiple food allergies. The follow-up procedures consisted of a double-blind placebo-controlled food challenge (DBPCFC) with CM t = 0, t = 1 (8 months), t = 2 (16 months), and t = 3 (24 months). At t = 1, eight (73%) of 11 children in the TG had a negative DBPCFC, versus four out of seven (57%) in the CG (BayesFactor = 0.61). At t = 3, nine of the 11 (82%) children in the TG and five of seven (71%) in the CG were tolerant (BayesFactor = 0.51). SIgE for CM reduced from a mean of 3.41 kU/L (SD = 5.63) in the TG to 1.24 kU/L (SD = 2.08) at the end of intervention, respectively a mean of 2.58 (SD = 3.32) in the CG to 0.63 kU/L (SD = 1.06). Product-related AEs were not reported. CM was successfully introduced in all children with negative DBPCFC. We found a standardised, well-defined heated CM protein powder that is safe for daily OIT treatment in a selected group of children with CMA. However, the benefits of inducing tolerance were not observed.

Introduction of Heated Cow's Milk Protein in Challenge-Proven Cow's Milk Allergic Children: The iAGE Study.

The introduction of baked milk products in cow's milk (CM) allergic children has previously been shown to accelerate induction tolerance in a selected group of children. However, there is no standardized baked milk product on the market. Recently, a new standardized, heated and glycated cow's milk protein (HP) product was developed. The aim of this study was to measure safety and tolerability of a new, well characterized heated CM protein (HP) product in cow's milk allergic (CMA) children between the age of 3 and 36 months. The children were recruited from seven clinics throughout The Netherlands. The HP product was introduced in six incremental doses under clinical supervision. Symptoms were registered after introduction of the HP product. Several questionnaires were filled out by parents of the children. Skin prick tests were performed with CM and HP product, sIgE to CM and α-lactalbumin (Bos d4), ß-lactoglobulin (Bos d5), serum albumin (Bos d 6), lactoferrin (Bos d7) and casein (Bos d8). Whereas 72% percent (18 out of 25) of the children tolerated the HP product, seven children experienced adverse events. Risk factors for intolerance to the HP product were higher skin prick test (SPT) histamine equivalent index (HEP) results with CM and the HP product, higher specific IgE levels against Bos d4 and Bos d8 levels and Bos d5 levels. In conclusion, the HP product was tolerated by 72% of the CM allergic children. Outcomes of SPT with CM and the HP product, as well as values of sIgE against caseins, α-lactalbumin, and ß-lactoglobulin may predict the tolerability of the HP product. Larger studies are needed to confirm these conclusions.