Multi OIT with Omalizumab
In 2014 Begin et al.19 first described a rush OIT protocol for up to five foods using omalizumab in 25 children. Cashew was included in 14 children, walnut in 9, pecan in 7, hazelnut in 3, and almond in 6. All children reached a 10-fold increase in their ED by two months on OIT and the maintenance dose (4000gm per food allergen) by nine months. During IED 13 children developed mild reactions. At hospital escalations, 13 mild reactions occurred per 227 doses. At-home dosing, 401 reactions were reported per 7530 doses, of which 385 were mild, 15 were moderate, and 1 was severe and required epinephrine. Home reactions occurred more frequently in the first months of therapy.
In a subsequent follow-up 27, 34 children were followed for over five years. After reaching maintenance with 2g protein for each food, the dose was reduced to 300mg for some participants based on a team-based decision. Participants were followed every 6-12 months, up to 62 months, through standard oral food challenges (OFCs), SPTs, and blood tests. Of the 18 children with cashew in OIT, 17 reduced the maintenance dose to 300mg. The corresponding numbers for walnut and hazelnut were 8/10 and 6/7 respectively. All children with pecan in their OIT continued the high dose, and all six children with almond in OIT changed to the low dose. At the end of the follow-up, each child was able to tolerate at least 2g protein during an OFC of their respective allergens, independent of the high or low dose. During the study, 1126 reactions were recorded. Of those most were mild, 40 were moderate, and 5 were severe. All severe reactions occurred in the high dose within the first 19 months of maintenance and involved skin and nasal symptoms. There were no serious adverse events or anaphylactic reactions. Epinephrine was used for mild-moderate reactions. The number of allergic reactions decreased over time. Safety did not differ between the low and the high-dose groups.
In a RDBPC multi-OIT study by Andorf et al.12, cashew was included in the OIT of 36 children, walnut in 25, hazelnut in 24, and almond in 7. After 36 weeks of OIT, a DBPCFC to implicated food was performed. In the omalizumab group, the proportion of children who passed a 2gr food protein per allergen was 20/25 for cashew, 17/20 for walnut, 16/17 for hazelnut, and 4/6 for almond. The corresponding numbers for the placebo group were 4/11 for cashew, 0/5 for walnut, 3/7 for hazelnut, and 0/1 for almond. Maintenance was achieved at 12 weeks in the omalizumab group versus 20 weeks in the placebo group. Throughout the study, there were no serious or severe adverse events. All patients in both groups experienced at least one adverse reaction during weeks 8-16. The omalizumab group had a significantly lower median per-participant percentage of OIT doses associated with any adverse events and a significantly lower median per-participant percentage of OIT doses associated with gastrointestinal and respiratory adverse events. There were 11 epinephrine uses, 5 in the omalizumab group and 6 in the placebo group.
Subsequently, the same group compared the efficacy of alternative maintenance dosing for six weeks on SU13. Having completed 30 months of omalizumab-facilitated multi-OIT and passed an OFC to at least 2gr per allergen, 60 participants were randomized to blindly receive 1g, 300mg, or 0mg per allergen as the maintenance dose for six weeks, followed by OFC to at least 2gr per allergen. In the 1gr group, desensitization was documented for 9/10 participants treated for cashew, 11/ 11 for walnut, 6/7 for hazelnut, and 2/2 for almond. The corresponding numbers for the 300mg group were 12/13 for cashew, 9/9 for walnut, 3/4 for hazelnut, and 1/1 for almond. During weeks 8-16, where OIT was co-administered with omalizumab, 42 participants reported at least one adverse event. Thereafter, all 60 participants had at least one adverse event, all but one classified as grade 1 or 2. Epinephrine was used eight times by six participants. No cases of life-threatening anaphylaxis or EoE were reported.