Phase 2, randomized multi oral immunotherapy with omalizumab ‘real life’ study

Abstract

Background: Oral immunotherapy (OIT) is frequently discontinued due to adverse events (AEs) and current data suggests that lowering OIT doses can minimize severity and frequency of AEs. However, the minimum daily dose that can enable desensitization and induce immune responses in multi-food OIT (mOIT) is unknown.Methods: Participants aged 2-25 years with multi-food allergies were pretreated with fixed-dose omalizumab (150 mg, 3 doses, every 4 weeks), and randomized 1:1 to receive mOIT to a total maintenance dose of either 300 or 1200 mg total protein, (total dose includes at least two and up to a max of five allergens) and then transitioned to real-food protein equivalents after 18 weeks of treatment. The primary endpoint was the proportion of subjects with increases in IgG4/IgE ratio of at least 2 allergens by ≥25% from baseline after 18 weeks of therapy. The primary efficacy and safety analyses were done in the intention-to-treat population.Results: Sixty participants were enrolled across two sites. Seventy percent of participants in both arms showed changes in sIgG4/sIgE ratio in at least 2 allergens with no difference between the treatment groups (OR [95% CI] = 1.00 [0.29, 3.49]). Overall, there were no differences in AEs between the 300 and 1200 mg groups (19% vs. 17%, p = .69), respectively. Conclusions:Our data suggest that plasma marker changes are induced early, even at a total protein dose of 300 mg inclusive of multiple allergens when mOIT is combined with fixed-dose omalizumab. Identification of optimal mOIT dosing with adjunct omalizumab is needed for the long-term success of OIT.

Combination of omalizumab with allergen immunotherapy versus immunotherapy alone for allergic diseases: A meta‐analysis of randomized controlled trials

“…A total of 474 results were filtered out of electronic databases (Figure 1). Forty‐two full‐text 22–32,35–65 publications were assessed for eligibility, and 31 articles 33,40–69 were excluded. Among the excluded, one registered Cochrane trial 69 was unfinished; twelve conference abstracts 56–67 had no full details; ten trials 33,40–48 met no inclusion criteria, in which the study by Takahashi et al 33 .…”

“…Forty-two full-text [22][23][24][25][26][27][28][29][30][31][32] publications were assessed for eligibility, and 31 articles 33, were excluded. Among the excluded, one registered Cochrane trial 69 was unfinished; twelve conference abstracts [56][57][58][59][60][61][62][63][64][65][66][67] had no full details; ten trials 33,[40][41][42][43][44][45][46][47][48] met no inclusion criteria, in which the study by Takahashi et al 33 was deleted from meta-analysis because no untreated children passed the double-blind placebo-controlled food challenge from the start of the study. Therefore, the trial did not pass ethical approval and was changed into an unblinded trial, 33 which might have artificially increased TMD and SU to allergens.…”

The origins and longevity of IgE responses as indicated by serological and cellular studies in mice and humans

“…Allergies likely to persist into adulthood are associated with higher amounts of serum IgE, with distinctive and diverse IgE‐binding epitope patterns on allergen, more diverse allergen recognition, and different V gene use of B cells relative to individuals that are tolerant to allergen or regularly ingesting it 67–73 . An allergy to one protein is also likely to copresent with allergies to others 28,60,74,75 . For example, egg allergic individuals are more likely to develop a peanut allergy, and cockroach‐sensitized individuals are often cosensitized to house dust mite 57,60 .…”

Food allergy, mechanisms, diagnosis and treatment: Innovation through a multi‐targeted approach

“…By selectively inhibiting specific mediators of the allergic pathway, these adjunct therapies are proposed to transiently reduce the likelihood of allergic reaction (Figure 3). The most studied biologic, omalizumab, an anti‐IgE antibody, has proven to be safe and effective as an adjunct to multi‐allergen OIT, 77,97 achieving desensitization to amounts of allergen beyond accidental ingestion (1–2 g protein per food) 98‐100 . Compared to placebo, participants receiving adjunct omalizumab prior to and during multifood OIT experienced reductions in the severity of AEs and a lower median per‐participant percentage of their OIT doses associated with any AE (68% vs 27%; p = 0·0082), with GI events reported as the most common AE in both groups 98,101 .…”

“…Recent years have witnessed significant developments in the pursuit of safe and effective treatment options for those with FA 76‐78 (Table 1). Landmark studies demonstrating the safety, efficacy of desensitization, and improvements in patient quality of life with oral immunotherapy (OIT) for food allergens led to the approval of peanut ( Arachis hypogaea ) Allergen Powder‐dnfp, the first oral peanut agent approved by the FDA and EMA for use in FA 9,78‐81 .…”