Desensitisation to cow’s milk, following partially or extensively hydrolysed formulae feeding regimens, in infants with allergy to cow’s milk: the DREAM RCT Synopsis (The DREAM study)

Guibas G, Brayshaw E, Brown M et al.   Efficacy Mech Eval 2026. https://doi.org/10.3310/GJGG7715

Background

Immunoglobulin E-mediated (immediate) cow’s milk allergy is one of the most frequent food allergies in infants, with a significant adverse impact on quality of life. There is no satisfactory treatment for cow’s milk allergy, and guidelines recommend milk avoidance, feeding with ‘hypoallergenic’ formulas (extensively hydrolysed formulas), emergency management of accidental reactions and waiting for the allergy to resolve spontaneously. Currently, the only potentially curative regimen is oral immunotherapy, that is, exposing patients to increasing doses of cow’s milk using a strictly controlled dose schedule. However, milk immunotherapy is not used in clinical practice due to risk of reactions. DREAM’s intention was to explore whether oral immunotherapy with a partially hydrolysed cow’s milk formula would be able to provide a safe and effective means of oral immunotherapy for milk-allergic infants.

Limitations

The trial was affected by a serious breach that led most of the participants to receive partially hydrolysed formula, even if randomised to extensively hydrolysed formula. It also ended prematurely due to unsatisfactory recruitment, and the main outcomes were not reached.

Methods

Trial flow chart. CM, cow’s milk; DBPCFC, double-blind placebo controlled food
challenge; eHF, extensively hydrolysed formula; OIT, oral immunotherapy;
pHF, partially hydrolysed formula; TC, telephone call; V1, visit 1; V2, visit 2.

DREAM was a two-arm, parallel-group, double-blind randomised controlled trial. Eligible patients were infants aged 6–12 months with convincing medical history of immunoglobulin E-mediated allergy to cow’s milk formula. Inclusion criteria included a titre of cow’s milk-specific immunoglobulin E equal or higher to 2 kU/l, or wheal equal or over 5 mm to skin prick test to milk.

Additionally, for the infants to be randomised, they needed to have a positive result to an open oral challenge either to partially hydrolysed formula or to milk. Participants were randomised to extensively hydrolysed formula or partially hydrolysed formula with a 1 : 1 ratio. Following randomisation, participants commenced free-feeding with the blinded product (or strict dose-based oral immunotherapy if they were not tolerant of the blinded product). The main outcome was the result of a double-blind, placebo-controlled food challenge to cow’s milk at the end of 1 year of free-feeding (or of dose-based immunotherapy) to establish if infants had become tolerant. As the trial was discontinued early on account of poor recruitment, no infant progressed to the double-blind, placebo-controlled food challenge.

Results

Out of 16 randomised participants who underwent an initial partially hydrolysed formula challenge, only 1 (6.25%) reacted to it (95% confidence interval 00.0 to 19.6). Hence, 93.75% of the allergic infants randomised in the trial tolerated partially hydrolysed formula. All fifteen infants that were found to be partially hydrolysed formula-tolerant also received partially hydrolysed formula free-feeding at home, on account of the serious breach. As per the trial’s criteria, these infants (and all randomised participants) were shown to be allergic to cow’s milk via either a positive open challenge to it (for the 15 partially hydrolysed formula-tolerant infants) or a positive open challenge to partially hydrolysed formula (for the single partially hydrolysed formula-reactive infant).

Conclusions

Partially hydrolysed formula was tolerated by the majority of well-characterised and confirmed cow’s milk-allergic infants in the DREAM trial.

Future work

Our findings demonstrate that partially hydrolysed formula holds promise as a potential oral immunotherapy medium in free-feeding oral immunotherapy regimens in future research. Further trials designed on the premise of partially hydrolysed formula oral immunotherapy are needed.

Funding

This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme as award number 17/60/44.

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