Almost two thirds of adults completing an oral immunotherapy (OIT) regimen for milk, peanut, sesame, egg, or tree nuts achieved full desensitization in the largest adult OIT cohort to date, researchers from the Shamir Medical Center Allergy Clinic in Zerifin, Israel and the Sackler School of Medicine, Tel Aviv University, reported in a retrospective review published recently in the journal Allergy.
“Our experience from over a decade of oral immunotherapy, treating many adults, shows favorable outcome and safety profile for non-milk allergens,” lead author Na’ama Epstein-Rigbi, MD, told Medscape Medical News, adding, “As for milk oral immunotherapy, this is a more difficult allergen to treat in all populations…in adults, success rates are significantly lower, with a profound amount of severe reactions.”
In the study, a total of 93 adults, median age 23 years, were treated between between April 2010 and December 2020, and compared to 1299 children and 309 adolescents treated during the same period.
The OIT program at Shamir Medical Center is ambulatory and begins with a 3-4 day dose-escalation phase in which the single highest tolerated dose (SHTD) is determined for each patient. This dose is then consumed once daily at home for 24 days, with further up-dosing and home treatment phases in which the dose can be escalated up to fourfold.
This treatment continues until the food-specific target dose for partial or full desensitization is reached. “Partial desensitization target doses (milk 180 mg protein; peanut 300 mg; tree nuts 300 mg; egg, 1500 mg, and sesame 240 mg protein) reflect a significantly increased protection in the case of accidental exposure,” note the authors, “while full desensitization target doses (milk 7200 mg protein; egg 6000 mg; peanut 3000 mg; tree-nuts 3900 mg and sesame 4000 mg protein) enable free consumption.”
More than half of the adult cohort (55.2%) were treated for milk allergy, while 5.2% were treated for egg allergy, 18.8% for peanut, 7.3% for sesame, and 13.5% for tree nuts.
In total, 61.5% of the adults reached full desensitization, 18.8% reached partial desensitization, and 19.8% failed the treatment. In comparison, full, partial, and failed desensitization occurred in 73.4%, 17.2%, and 9.3% of children and 69.6%, 20.7%, and 9.7% of adolescents.
In adults, anaphylactic reactions were found to be the most prevalent reason for both partial desensitization (54%) and treatment failure (70%), with adults having a significantly higher rate of severe adverse reactions requiring epinephrine during in-clinic up-dosing (49% compared with 15.9% of children and 26.5% of adolescents; P < .0001 for both), and similarly during home treatment (22.9% of adults, 17.5% of adolescents, and 12.4% of children).
Milk Most Strongly Associated With Treatment Failure
Multivariate analysis showed that milk allergy was most strongly associated with treatment failure in the entire population (odds ratio [OR], 3.63, P < .001), and that treatment failure rates were significantly higher in milk OIT patients who were adult (28.3%) compared with children (14.3%, P = .015) and adolescents (14.1%, P = .022). Adults treated with milk OIT had a significantly higher rate of reactions requiring epinephrine — both in-clinic and during home treatment — compared with children and adolescents.
Despite the higher rates of treatment failure and adverse reactions among adults, “most of them achieve full desensitization,” note the authors, adding that “the increased rate of adverse reactions and treatment failure is driven by milk OIT. In adult patients undergoing OIT for other foods such as peanut, tree nuts, sesame, and egg, the rates of severe reactions at home and of treatment failure are low and comparable to the rates in younger patients. Importantly, the rate of full desensitization is high in non-milk treated adults, reaching over 80%, and similar to that of children and adolescents.”
“Our main understanding is that unlike non-milk allergens, in which patients can be encouraged to undergo oral immunotherapy at all ages, milk allergic patients should be encouraged to treatment at young ages, to increase success rates,” explained Epstein-Rigbi.
Given the paucity of data on adult OIT, the findings “should be cautiously encouraging to clinicians and adult food allergy patients that OIT may allow them to lead more normal lives,” commented Richard Wasserman, MD, PhD, an authority on the topic who was not involved in the research.
Adding that the Israeli group “has made another valuable contribution” to the field, Wasserman, an allergist/immunologist with Allergy Partners of North Texas in Dallas, noted the important distinction between the study’s two categories of desensitization. “While a goal for some patients is ad lib consumption of the OIT food, so-called ‘free eating’, the primary OIT goal for most patients is the reduction in the risk of a reaction from accidental exposure.”
He also said the higher failure rate with milk OIT is “not surprising. There have been anecdotal comments among experienced OIT allergists that milk OIT has been particularly difficult for their patients.” However, he said, since most patients allergic to milk or egg have outgrown their allergy by age 18, adult patients still allergic to milk or egg “may represent a subpopulation of food-allergic patients representing a unique phenotype.”
But Wasserman cautioned against extrapolating the Israeli findings to North America, “because their dose escalation regimen is very different from that used by most OIT centers in North America, which do dose increases weekly or biweekly until the target dose is reached”.
“I am not sure this impacts our findings,” Epstein-Rigbi responded, adding that although she is not overly familiar with North American protocols, “I do know that one major difference is that our protocol is individualized…[and]…usually preset, non-individualized protocols have better safety profiles than individualized ones.”
No study funding was declared. The authors report no relevant financial relationships. Wasserman is the vice president of Food Allergy Support Team, a charitable organization with the mission of supporting OIT allergists, and he is the investigator for Cour Pharmaceuticals, which has an early-stage treatment for peanut allergy.
Allergy. Published online October 3, 2022. Full text
Kate Johnson is a Montreal-based freelance medical journalist who has been writing for more than 30 years about all areas of medicine.