66% of kids grow out cow’s milk allergy, even if they completely avoid it. But rate rises to nearly 90% if baked milk introduced. And less restrictive diet good for everyone, of course.

Salmivesi RCT from Finland 2012 – n=28, age 6-14. 81% using daily milk 6400mg protein at 12 months. First dose milk 0.06mg – 8 further observed doses (0.12mg day 8; 0.24mg day 15; 2.0mg day 36 [big jump!]; 4.0mg day 38 [2 days later!?]; 8.0mg day 42; 40mg [big jump again!] day 57; 80mg day 64; and 160mg on day 78) with other dose increases done at home. Monitored for 2hr in clinic. Final dose of 6400mg (=200ml) was given at home (!) on day 162.

Oral immunotherapy (OIT) for severe milk allergy (IgE >85 or low eliciting dose):  at 1yr 36% tolerated 150ml, 54% 5-150ml (good enough for accidental exposure). 10% could not complete protocol. [reference?]

DRACMA update on milk immunotherapy (2021) mostly fresh milk used in research. Randomized trials looked at kids aged 2-14, mean 8. Non randomized had wider range. 67% tolerated 150ml (cf 2.2% of controls), 78% tolerated 5-150ml (=swig protection) (cf 3.3% of controls). Anaphylaxis rate of 5.5 per person-years (although not always defined, and not always usual definition). 63% used IM adrenaline!?

6.9% developed EOE but rarely biopsy confirmed. No deaths.

2–8 weeks after discontinuation of successful OIT, tolerance of cow’s milk persisted in only 36% (20%–91%). So you have to persevere life long, probably.

Quality of life badly reported – only 5 studies. 1 study found parents reported better QOL in 37%, worse in 26%, and unchanged in 38%! 2 conference abstracts reported improved QOL or at least reduced anxiety in general and reduced fear of unexpected reaction. Some studies found worse QOL! Certainty of evidence overall v low…

Only 1 trial and 2 non randomized studies of baked milk OIT! In the 1 RCT of baked milk, 73% achieved tolerance at 12 months (cf none of control group) – other studies did not find evidence of effectiveness however (meta-analysis of Anagnostou. Tolerance to heated or baked milk may be temporary and diminish within a few years. Dantzer. 20% required adrenaline! Only some children assessed for QOL, with evidence of benefit – of the parents studied, no improvement in QOL! [Dantzer and Dunlop 2021]. Low desensitization rate for unheated milk means persisting concern about exposure in real life despite less frequent adverse reactions (8%–33%).

Other studies did not find this relationship, which is consistent with the meta-analysis results of Anagnostou et al. (41). Tolerance to heated or baked milk may be temporary and diminish within a few years. Dantzer et al. found that a protocol involving gradually increasing doses of baked milk was effective in promoting desensitization (73% achieved end dose of 4000mg cf 0% of controls).  Mean age 11. “This suggests that the initial dose [and then building] may influence the efficacy of desensitization.” [Yan Wang, China – Front. Immunol., 04 June 2025]

4% rate of biopsy proven EOE – note EoE typically emerges approximately 2.8 years after initiating the maintenance phase so many studies will miss…

Longer duration better. None of the studies reported on sustained unresponsiveness.

Only Dantzer study reported quality of life! 

Highlights “a dire need for a standardization in outcome assessment and reporting,” and that successful completion of OFC needs to be validated as a predictor of “real world” success. [Natasha trial will hopefully clarify further…]

Separate article on OIT recommendations – apart from balancing risks and benefits, recommends using omalizumab (monoclonal anti-IgE) in advance and in initial stages of oral immunotherapy with unheated cow’s milk. Inferring from limited evidence (use in other food allergies, mostly) that risk of anaphylaxis reduced (RR0.34 but not significant!). Not really any downside? (But costs at least £256 per dose, maybe double? Lasts a month?). Plus, does not recommend baked milk OIT as very low certainty of benefit. More evidence on effect, risks, QOL benefit obviously required.  

Sublingual/epicutaneous immunotherapy (SLIT) for milk? Not much evidence – low rate of success and high rate of relapse.

[EGPHAN 2023, Frontiers in Pediatrics 2019; BMJ cmpa article sept 2013]

Rush study from Japan used microwaved milk – microwaved for 100s at 550W (!). Dosing was 2–4 times a day in hospital for several days (frequent adverse events) aiming for 200 mL dose (total daily, I assume). If not achieved, dose increases changed to 1ml per day. At 200ml, dosing changed to once a day. After 2 months of maintenance, length of time in the microwave gradually reduced.

Another Japanese study looked at using heated milk powder (3 mins at 125degC) vs unheated milk. Rush protocol (5 days in hospital) up to maintenance of just 3ml daily. At 1 year, 35% and 18% in the HM group and 50% and 31% in UM group passed the 3 and 25 mL OFCs, respectively, so not great efficacy. Rates of moderate or severe symptoms significantly lower (halved) in the heated milk group however.

Natasha Trial is looking at Peanut or cow’s milk OIT in UK – groups are Peanut age 6-23yrs, Peanut age 2-3yrs, Cow’s milk age 3-23yrs. Using everyday food products. Final results expected 2027.

Outcome

In small Korean study of kids aged 3-10, 83% has sustained unresponsiveness (stopped cow’s milk for 4 weeks, following 12 months of maintenance.

In a study of OIT plus omalizumab, about half had sustained unresponsiveness.

Duration of treatment appears to be key – in Japanese study, 2 years treatment had significantly more SU cf 1 yr treatment. Review here.