Table 3. Representative milk oral immunotherapy clinical trials.
| Design & reference | Sample: size & age | Protocol: duration & daily maintenance dose | Outcome (by ITT) and other significant findings | Notable adverse events |
|---|---|---|---|---|
| Milk OIT, open-label in highly sensitized | 21 subjects | 6 months | Milk OIT induced desensitization to daily 200 ml dose in 71% of subjects considered to have severe cow milk allergy | No reported EAI 14% developed moderate symptoms on first dose 14% had dose-limiting symptoms during build-up |
| Meglio et al. 2004 | 5–10 years | 200 mL | ||
| Milk and egg OIT vs avoidance in young children, RCT | 14 milk 11 egg 20 avoidance |
Mean 21 months | 64% of OIT subjects were able to integrate allergenic food into the diet, compared to 35% of avoidance group (P=0.05); 36% of OIT group demonstrated 2-month SU | No severe AE. No EAI 9 AE-related withdrawals All active had AE, 4 with moderate AE. Among controls, 5 had moderate symptoms on accidental exposures |
| Staden et al. 2007 | Median 2.5 years (range 1-12 years) | 100 mL cow milk 1.6 g egg |
||
| Milk OIT vs placebo, RCT | 12 active 7 placebo |
6 months | Milk OIT induced desensitization, with median eliciting dose in active subject 5,140 mg compared to 40 mg in placebo (P<0.001) | 1% of active doses elicited multi-system AE, vs 0 in placebo (P=0.01); 1 of 12 active withdrew due to AE |
| Skripak et al. 2008 | 6–17 years | 15 mL | ||
| Milk OIT, Open-label follow up of Skripak 2008. | 15 subjects, tolerant of 75 mL after above OIT | Median 4 months open-label following 6 months blinded | Milk OIT induced desensitization to between 90 and 480 mL in 87%, with safety concerns | EoE in 1 subject. 6 EAI in 4 subjects. Multi-system reaction decreased from 11% in first 3 months to 4.8% in subsequent month |
| Narisety et al. 2009 | 15 mL | |||
| Milk OIT with gradual build-up vs placebo, RCT | 15 active 15 placebo |
4.5 mo | Milk OIT with gradual outpatient build-up induced desensitization in 66% of active, vs 0 in placebo, with safety concerns | Among active group, 3 patients experienced severe AE with 2 EAI; 7 mild AE; 3 had no AE |
| Pajno et al. 2010 | 4-10 years | 200 mL | ||
| Milk OIT vs placebo, RCT in young children | 30 active 30 placebo |
1 year | Among young subjects, milk OIT induced 200 mL-desensitization in 90% on active, vs 23% in placebo, with safety concerns | 2 EAI. 37% of subjects experienced multi-system reaction. 2 AE-related withdrawals |
| Martorell et al. 2011 | 2-3 years | 200 mL | ||
| Low-dose OIT vs avoidance, in highly sensitized | 12 active 25 avoidance |
1 year, with 5-day inpatient build-up | In a highly sensitized group, low-dose OIT protocol induced 3 mL-desensitization in 58% of active and 14% of controls (P=0.018); and 25 mL-desensitization in 33% of active vs 0 of controls (P=0.007), with good safety profile | 1 EAI after home dose, given for cough; no AE-related withdrawals |
| Yanagida et al. 2015 | 6-13 years | 3 mL |
AE, adverse event; EoE, eosinophilic esophagitis; EAI, epinephrine auto-injector; ITT, intention to treat; OIT, oral immunotherapy; RCT, randomized controlled trial; SU, sustained unresponsiveness.