Background Oral immunotherapy (OIT) is an effective experimental food allergy treatment that is limited by treatment withdrawal and the frequent reversibility of desensitization if interrupted. Newly ...diagnosed preschool children may have clinical and immunological characteristics more amenable to treatment. Objective We sought to test the safety, effectiveness, and feasibility of early OIT (E-OIT) in the treatment of peanut allergy. Methods We enrolled 40 children aged 9 to 36 months with suspected or known peanut allergy. Qualifying subjects reacted to peanut during an entry food challenge and were block-randomized 1:1 to receive E-OIT at goal maintenance doses of 300 or 3000 mg/d in a double-blinded fashion. The primary end point, sustained unresponsiveness at 4 weeks after stopping early intervention oral immunotherapy (4-SU), was assessed by double-blinded, placebo-controlled food challenge either upon achieving 4 prespecified criteria, or after 3 maintenance years. Peanut-specific immune responses were serially analyzed. Outcomes were compared with 154 matched standard-care controls. Results Of 40 consented subjects, 3 (7.5%) did not qualify. Overall, 29 of 37 (78%) in the intent-to-treat analysis achieved 4-SU (300-mg arm, 17 of 20 85%; 3000 mg, 12 of 17 71%, P = .43) over a median of 29 months. Per-protocol, the overall proportion achieving 4-SU was 29 of 32 (91%). Peanut-specific IgE levels significantly declined in E-OIT-treated children, who were 19 times more likely to successfully consume dietary peanut than matched standard-care controls, in whom peanut-specific IgE levels significantly increased (relative risk, 19.42; 95% CI, 8.7-43.7; P < .001). Allergic side effects during E-OIT were common but all were mild to moderate. Conclusions At both doses tested, E-OIT had an acceptable safety profile and was highly successful in rapidly suppressing allergic immune responses and achieving safe dietary reintroduction.
Background Although peanut oral immunotherapy (OIT) has been conclusively shown to cause desensitization, it is currently unknown whether clinical protection persists after stopping therapy. ...Objective Our primary objective was to determine whether peanut OIT can induce sustained unresponsiveness after withdrawal of OIT. Methods We conducted a pilot clinical trial of peanut OIT at 2 US centers. Subjects age 1 to 16 years were recruited and treated for up to 5 years with peanut OIT. The protocol was modified over time to permit dose increases to a maximum of 4000 mg/d peanut protein. Blood was collected at multiple time points. Clinical end points were measured with 5000-mg double-blinded, placebo-controlled food challenges once specific criteria were met. Results Of the 39 subjects originally enrolled, 24 completed the protocol and had evaluable outcomes. Twelve (50%) of 24 successfully passed a challenge 1 month after stopping OIT and achieved sustained unresponsiveness. Peanut was added to the diet. At baseline and the time of challenge, such subjects had smaller skin test results, as well as lower IgE levels specific for peanut, Ara h 1, and Ara h 2 and lower ratios of peanut-specific IgE/total IgE compared with subjects not passing. There were no differences in peanut IgG4 levels or functional activity at the end of the study. Conclusions This is the first demonstration of sustained unresponsiveness after peanut OIT, occurring in half of subjects treated for up to 5 years. OIT favorably modified the peanut-specific immune response in all subjects completing the protocol. Smaller skin test results and lower allergen-specific IgE levels were predictive of successful outcome.
Background Though peanut oral immunotherapy (OIT) is a promising investigational therapy, its potential is limited by substantial adverse events (AEs), which are relatively understudied. Objective A ...retrospective analysis was conducted, pooling data from 3 pediatric peanut OIT trials, comprising the largest analysis of peanut OIT safety to date. Methods We pooled data from 104 children with peanut allergy from 3 peanut OIT studies. We catalogued AEs from parental reports, daily symptom diaries, and dose escalations. We included events that were considered likely related to OIT and identified potential baseline predictors of higher AE rates using generalized linear regression models. Results Eighty percent of subjects experienced likely related AEs during OIT (72% during buildup and 47% during maintenance). Of these AEs, over 90% occurred while at home. Approximately 42% of subjects experienced systemic reactions, and 49% experienced gastrointestinal symptoms. Twenty percent of subjects dropped out, with half (10% of the overall group) due to persistent gastrointestinal symptoms. Baseline allergic rhinitis (AR) and peanut SPT wheal size were significant predictors of higher overall AE rates. SPT wheal size predicted increased gastrointestinal AEs, and AR predicted increased systemic reactions. Over the course of OIT, 61% of subjects received treatment for likely related AEs, 59% with antihistamines and 12% with epinephrine. Conclusions Peanut OIT is associated with frequent AEs, with rates declining over time, and most graded mild. However, systemic reactions and intolerable gastrointestinal AEs do occur and are significantly associated with AR and peanut SPT wheal size, respectively. Further study is needed of predictive biomarkers and the overall risks and benefits of OIT.
Background Oral immunotherapy (OIT) offers a promising therapeutic option for peanut allergy. Given that during OIT an allergic patient ingests an allergen that could potentially cause a serious ...reaction, the safety of OIT is of particular concern. Objective The purpose of this study was to examine safety during the initial escalation day, buildup phase, and home dosing phase in subjects enrolled in a peanut OIT study. Methods Skin, upper respiratory tract, chest, and abdominal symptoms were recorded with initial escalation day and buildup phase dosings. Subjects also maintained daily diaries detailing symptoms after each home dosing. A statistical analysis of these data was performed. Results Twenty of 28 patients completed all phases of the study. During the initial escalation day, upper respiratory tract (79%) and abdominal (68%) symptoms were the most likely symptoms experienced. The risk of mild wheezing during the initial escalation day was 18%. The probability of having any symptoms after a buildup phase dose was 46%, with a risk of 29% for upper respiratory tract symptoms and 24% for skin symptoms. The risk of reaction with any home dose was 3.5%. Upper respiratory tract (1.2%) and skin (1.1%) symptoms were the most likely after home doses. Treatment was given with 0.7% of home doses. Two subjects received epinephrine after 1 home dose each. Conclusions Subjects were more likely to have significant allergic symptoms during the initial escalation day when they were in a closely monitored setting than during other phases of the study. Allergic reactions with home doses were rare.
...1 subject had several systemic reactions when menses was coupled with exercise despite no symptoms with daily dosing in the interval between episodes and was eventually withdrawn from the study. ...Age at reaction (mo) Pattern Reaction Dose (mg) Length of time on OIT (mo) Length of time on dose Baseline IgE level (kU/L) IgE level at time of reaction (kU/L) Treatment Recommendations to this subject 1 70 Fever AE, LR 300 12 5 mo 23.6 13.9 H1, E, A Hold dose if ill 2 131 Fever AE, U, LR 1200 19 3 mo >100 136.5 H1, E, CS, A Hold dose if ill 3 38 Asthma LR 300 10 4 mo 22.7 9.3 H1, A Start inhaled CS 4 83 Empty stomach U, LR, G 1800 27 7 mo >100 115 H1, A Take all doses with meal 5 102 Exertion LR 2400 49 2 mo 58.3 4.7 H1, A Avoid exercise for 2 h after dose 6 99 Exertion U, LR 3000 47 2 d 73.1 7.3 H1, CS Avoid exercise for 2 h after dose; decrease dose to 2400 mg 7 145 Menses and exertion AE,U, UR, LR, G 4000 20 9 mo 85.1 59.5 H1, E, CS Discontinued participation in study after second occurrence Table I Examples of reactions during peanut OIT home dosing A, Albuterol; AE, angioedema; CS, corticosteroids; E, epinephrine; G, gastrointestinal; H1, H1 antagonist; LR, lower respiratory; OIT, oral immunotherapy; U, urticaria; UR, upper respiratory.
Background There is no current active treatment for food allergy. Traditional injection immunotherapy has been proved unsafe, and thus there is a need for other forms of immunotherapy. Objective The ...purpose was to study the safety and immunologic effects of egg oral immunotherapy (OIT). The short-term goal was to desensitize subjects to protect against accidental ingestion reactions. The eventual goal was to induce lasting clinical and immunologic tolerance. Methods Subjects with a history of egg allergy but without a history of anaphylaxis to egg underwent a 24-month egg OIT protocol involving modified rush, build-up, and maintenance phases. Double-blind, placebo-controlled food challenges were performed at study conclusion. Egg-specific IgE and IgG concentrations were followed. Results Seven subjects completed the protocol. Egg-specific IgG concentrations increased significantly, whereas egg-specific IgE concentrations did not significantly change. Three subjects tolerated known or possible accidental egg ingestions while receiving OIT. During double-blind, placebo-controlled food challenges at study conclusion, all tolerated significantly more egg protein than at study onset and than that found in the typical accidental exposure. Two subjects demonstrated oral tolerance. Conclusion This study provides proof of concept that OIT can be safely used for patients with egg allergy without a history of anaphylaxis to egg. Egg OIT does not heighten sensitivity to egg and might protect against reaction on accidental ingestion. Whether OIT will induce clinical oral tolerance cannot be concluded from this initial cohort. Clinical implications Use of allergen-specific OIT to protect subjects with food allergy from reaction on accidental ingestion would represent a significant paradigm change in the treatment of food allergy.
Background Patients with peanut allergy have highly stable pathologic antibody repertoires to the immunodominant B-cell epitopes of the major peanut allergens Ara h 1 to 3. Objective We used a ...peptide microarray technique to analyze the effect of treatment with peanut oral immunotherapy (OIT) on such repertoires. Methods Measurements of total peanut-specific IgE (psIgE) and peanut-specific IgG4 (psIgG4 ) were made with CAP-FEIA. We analyzed sera from 22 patients with OIT and 6 control subjects and measured serum specific IgE and IgG4 binding to epitopes of Ara h 1 to 3 using a high-throughput peptide microarray technique. Antibody affinity was measured by using a competitive peptide microarray, as previously described. Results At baseline, psIgE and psIgG4 diversity was similar between patients and control subjects, and there was broad variation in epitope recognition. After a median of 41 months of OIT, polyclonal psIgG4 levels increased from a median of 0.3 μg/mL (interquartile range 25% to 75%, 0.1-0.43 μg/mL) at baseline to 10.5 μg/mL (interquartile range 25% to 75%, 3.95-45.48 μg/mL; P < .0001) and included de novo specificities. psIgE levels were reduced from a median baseline of 85.45 kUA /L (23.05-101.0 kUA /L) to 7.75 kUA /L (2.58-30.55 kUA /L, P < .0001). Affinity was unaffected. Although the psIgE repertoire contracted in most OIT-treated patients, several subjects generated new IgE specificities, even as the total psIgE level decreased. Global epitope-specific shifts from IgE to IgG4 binding occurred, including at an informative epitope of Ara h 2. Conclusion OIT differentially alters Ara h 1 to 3 binding patterns. These changes are variable between patients, are not observed in control subjects, and include a progressive polyclonal increase in IgG4 levels, with concurrent reduction in IgE amount and diversity.
Eosinophilic esophagitis during peanut oral immunotherapy with omalizumab Burk, Caitlin M; Dellon, Evan S; Steele, Pamela H ...
Journal of allergy and clinical immunology. In practice/The Journal of allergy and clinical immunology. In practice,
03/2017, Letnik:
5, Številka:
2
Journal Article
Rationale Desensitization has been shown with sublingual immunotherapy (SLIT) in children with peanut allergy with a median reaction threshold of 1710 mg of peanut protein after 12 months of therapy ...using a 2 mg maintenance dose.
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