Food Allergen Immunotherapy in the Treatment of Patients with IgE-Mediated Food Allergy
Abstract
:1. Introduction
2. Mechanisms of Food Allergen Immunotherapy
3. Oral Immunotherapy (OIT)
3.1. Efficacy of OIT
3.1.1. Milk OIT
3.1.2. Egg OIT
3.1.3. Peanut OIT
3.1.4. OIT to Other Food Allergens
3.2. Safety of OIT
4. Sublingual Immunotherapy (SLIT)
4.1. Efficacy of SLIT
Author (Year) | Type of Study | Allergen | Participants | Duration | Efficacy | Safety |
---|---|---|---|---|---|---|
Kinaciyan et al. (2018) [68] | Double-blind, placebo-RCT | Apple protein | n = 60 (aged 18–65 y) 1:1:1 = placebo:rMal d 1:rBet v 1 | 16 weeks | rMal d 1 vs placebo and rBet v 1 (p = 0.001 and p = 0.038) SLIT rMal d 1 enhanced IgG4/IgE ratios (p = 0.012). | Mainly local AE to both formulations |
Enrique et al. (2005) [69] | Double-blind placebo-RCT | standardized hazelnut extract | n = 23 (19–53 y) Active group n = 12 Placebo group n = 11 | 12 weeks | Median SCD hazelnut SLIT p = 0.02 50% active group reached highest dose (20 g) | AE Mild; Systemic reactions 0.2% |
Garrido-Fernández et al. (2014) [70] | Double-blind placebo-RCT | peach extract | n = 31 (18–65 y) Treatment group:placebo = 2:1 | 6 months | Median SCD p = 0.002 3-fold improvement in tolerance in active group p = 0.065 | No data. All subjects that started treatment also have finished it |
Keet et al. (2012) [71] | Open- label exploratory RCT | milk | n = 30 (6–17 y) | 60 weeks | 1/10 SLIT/SLIT group, 6/10 SLIT/OITB group, 8/10 SLIT/OITA group—SCD DBPCFC 8-g (p = 0.002, SLIT vs. OIT) End of study: p = 0.09 SLIT vs. OIT | Symptoms 29% of SLIT doses and 23% of OIT doses. no significant differences in the rate of total AE SLIT and OIT p = 0.73, 0.70, and 0.50, respectively Multisystem symptoms OIT vs. SLIT p < 0.001 |
Kim et al. (2011) [72] | Double-blind placebo-RCT | peanut | n = 18 (1–11 y) Peanut SLIT n = 11 Placebo n = 7 | 12 months (6 months build-up and 6 months MD) | Median SCD peanut SLIT vs. placebo p = 0.011 | Transient oropharyngeal itching most common AE 0.26% antihistamine treatment 0.02% doses required albuterol for mild wheezing |
Kim et al. (2019) [73] | Open-label extension RCT | peanut | n = 48 (1–11 y) 2-mg peanut SLIT MD | 5 years | 67% SCD ≥ 750 mg on DBPCFCs. median SCD 1750 mg 25% (12/48) 5000-mg DBPCFC; 10/12 SU after 2 to 4 weeks | AE 4.78%; transient oropharyngeal itching most common Antihistamine use 0.21% No epinephrine |
Kim et al. (2023) [74] | Open-label, prospective RCT | peanut | n = 54 (1–11 y) 4 mg peanut SLIT MD | 48 weeks | Mean SCD (0–48 month) p < 0.0001 36% SCD of 5000 mg 70.2% SCD ≥ 800 mg | Dosing AE 4% of doses |
Fleischer et al. (2013) [75] | Multicenter placebo-RCT | peanut | n = 40 (12–40, median age 15 y) Placebo group n = 20 Intervention group n = 20 | The first phase 44 weeks (68 weeks data) | Week 44: RR intervention group vs placebo p < 0.001 median SCD week 44 vs. baseline in intervention group p < 0.01 Week 68: median SCD week 68 vs. 48 p = 0.05, week 68 vs. baseline p = 0.009 Week 44 Crossover: median SCD p = 0.02 | Week 44: transient oropharyngeal itching most common AE 1.1% of total doses required treatment. Crossover High Dose subjects: 2.9% doses required treatment 1 subject had anaphylaxis |
Burks et al. (2015) [76] | Long-term follow-up RCT | peanut | n = 40 (12–40 y) | From week 68 to 164 | 4/37 (10.8%) of SLIT participants fully desensitized to 10 g of peanut powder and SU | 98% of the doses were tolerated without AE no severe symptoms no epinephrine |
4.2. Safety of SLIT
5. Epicutaneous Immunotherapy (EPIT)
5.1. Efficacy of EPIT
Author (Year) | Type of Study | Allergen | Participants | Duration | Efficacy | Safety |
---|---|---|---|---|---|---|
Sampson et al. (2017) [81] VIPES | multicentre double-blind placebo-RCT + 2-year, open-label extension study | peanut | n = 221 (6–55 y) randomization 1:1:1:1 Open Label Extension Study, n = 171 | 12 months + 2-year, open-label extension study | RR month 12 VP250-μg vs placebo p = 0.01; % responders only significant for the VP250 p = 0.04 RR in children VP250 vs. placebo p = 0.008; Open-label Extension study: RR at months 12 and 24 in the overall population 59.7% (89/149) and 64.5% (80/124) | AEs largely local skin reactions |
Jones et al. (2017) [86] CoFAR6 | Multicentre Double-blind placebo-RCT | peanut | n = 74 (4–25 y), median age 8.2 n = 25 placebo nVP100 = 24 or nVP250 = 25 | 52 weeks | Treatment success: VP100 vs. PLB p = 0.005;VP250 vs. PLB p = 0.003; VP100 vs. VP250, p = 0.48 -medium change SCD: Among 3 groups p = 0.003; Placebo vs. VP100 p = 0.014; Placebo vs. VP250 p = 0.003; VP100 vs. VP25 p = 0.41 -success better in younger participants (6–11 y) p = 0.006 | AEs largely mild Non–patch-site AE: 0.2% of placebo and VP100 doses and 0.1% of VP250 doses |
Scurlock et al. (2021) [87] Follow-up CoFAR | Open-label RCT | peanut | n = 74 (4–25 y) | 130 weeks | Desensitization: 5% PLB-VP250, 20.8% VP100-VP250, 36% VP250 median SCD change from baseline of 11.5 mg, 141.5 mg, and 400 mg, respectively. Post-hoc analysis of change in SCD week 52–130: overall p = 0.29, within treatment groups PLB-VP250 p = 0.32; VP100-VP250 p = 0.32; VP250 p = 0.10. | most dosing AE mild |
Fleischer et al. (2019) [88] PEPITES | multicentre Double-blind placebo-RCT | peanut | n = 356 (4–11 y) n = 238 peanut protein 250 μg; n = 118 placebo | 12 months | The percentage difference in responders VP250-μg vs placebo p < 0.001 The lower bound of the 95% CI of the difference 12.4% crossed the prespecified lower limit of 15% | AE mostly mild 4 of 238 participants (1.7%) in the active group discontinued treatment due to AEs. |
Fleischer et al. (2020) [89] PEOPLE | Open-label follow-up RCT | peanut | n = 198 (4–11) | 5 years (4–5 y in progress) | 141 (71%) subjects DBPCFC at month 36 At month 36: 51.8% subjects ED > 1000 mg, At month 12: 40.4%; 75.9% increased ED compared with baseline; 13.5% tolerated DBPCFC of 5444 mg. Median CRD from 144 to 944 mg; SU 14 of 18 subjects | AEs mild or moderate |
Greenhawt et al. (2023) [90] EPITOPE | multicentre Double-blind placebo-RCT | peanut | n = 362 (1–3 y), the median age: 2.5 y intervention: placebo 244:118 ED < 300 mg | 12 months | Intervention group 67.0% vs. placebo group 33.5%, p < 0.001) the mean change in CRD intervention vs placebo group 3.13 (p < 0.001) ED intervention vs placebo group 2.96 (p < 0.001) | AE mostly mild Serious AE 8.6% intervention group 2.5% placebo group; anaphylaxis 7.8% and 3.4%; Serious treatment-related AE 0.4% intervention group, no placebo group. Treatment-related anaphylaxis 1.6% intervention group, none placebo group. |
Dupont et al. (2010) [91] | Double-blind placebo-RCT | Milk | n = 19 (3 months–15 y) n = 10 active group n = 9 placebo group | 3 months | PP population CTD (0–90 day) p = 0.18 | AE mild |
Spergel et al. (2020) [92] SMILEE | pilot double- blind placebo- RCT (+ open-label extension study) | Milk | n = 20 (Age: 4–11 y) n = 15 active group, n = 5 placebo group | 11 months + 11 months open label | VM500 group mean eos/hpf 50.1 ± 43.97 vs. the placebo group 48.20 ± 56.98 eos/hpf VM500 group lower mean eos/hpf count p = 0.038 Open label phase: 47% response mean values of fewer than 15 eos/hpf | Improvement in endoscopy scores in treatment group AE mild |
Pongracic et al. (2022) [93] REALISE | multicentre Double-blind placebo-RCT + ongoing open-label active treatment | peanut | n = 393, (4–11 y) 3:1 = VP250:placebo for 6 months. 72.3% participants with history of peanut anaphylaxis | 3 years (6 months double blind placebo control) | REALISE was without a DBPCFC and therefore had no efficacy assessment. | 82.7% mild AE; 36.9% moderate AE 1.3% severe AE overall |
5.2. Safety of EPIT
6. Food Allergen Immunotherapy and Biologics
7. Discussion
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Reference | Design | Sample | Participants Characteristic | Form of Allergen | Duration | Maintenance Dose | Efficacy | Safety |
---|---|---|---|---|---|---|---|---|
milk | ||||||||
Skripak et al. (2008) [40] | Double-blind, placebo-RCT | n = 20 (6–17 y) OIT: n = 12 Placebo: n = 7 | Positive DBPCFC to 2.5 g MP. Baseline median threshold: 40 mg MP | Milk powder | 5–6 months | 500 mg MP (15 mL of milk) | Median threshold after OIT: OIT: 5140 mg Placebo: 40 mg (p = 0.003) | AE/total doses: OIT 45.4%, placebo: 11.2% AE/each participant: OIT 35%, placebo group 1%. AAR: OIT 1%, placebo 0% |
Narisety et al. (2009) [41] | Extension of previous p study [40] | n = 15 (6–16 y) | Negative DBPCFC to 2.5 g MP | Dairy products | 3–17 months | Daily diary intake at home | OFC to 16 g MP: Negative for 33% | AE/total doses: 17% Epinephrine: 0.2% reaction |
Inuo et al. (2018) [46] | Double-blind, placebo-RCT, 2 phase: 8 weeks pHF or eHF, then 8 weeks all on eHF | n= 25 (1–9 y) 2 group: active: pHF-pHF (n = 13) placebo: eHF-eHF (n = 12) | History of systemic reactions to milk. Positive OFC to 20 mL rCMF | pHF | 16 weeks | 0.5–20 mL of pHF | OFC with rCMF: Threshold at the end of first phase: Significantly elevated in pHF.pHF (p = 0.048) | AE: not severe reaction 2 participants in active group mild reaction |
Nagakura et al. (2021) [44] | Open-label RCT | n = 33, >5 y HM-OIT: (n = 17) UM-OIT (n = 16) | Positive DBPCFC on 3-mL HM, History of milk anaphylaxis | HM vs. UM | 1 year | 3 mL milk | Desensitization to 3 mL and 25 mL: HM-OIT: 35%, 18% UM-OIT; 50%, 31% (p = 0.34, p = 0.43) | AE at home dose: HM: OIT: 8.1%; UM-OIT: 9.6% AE moderate/severe at home: HM-OIT: 0.7%; UM-OIT: 1.4% (p = 0.0002) |
Maeda et al. (2021) [42] | Open-label RCT | n = 28, 3–12 y OIT: n = 14 Control: n = 14 | Positive OFC to 10 mL milk | Liquid milk | 1 year | 100 mL milk | OFC to 100 mL milk: OIT: 50% Control: 0% (p < 0.01) | AE requiring adrenaline: OIT: 43% participants Control: 0% participants |
Van Boven et al. (2023) [45] | RCT follow-up study | n = 18 (6–36 months) OIT: n = 11 control: n = 7 | Milk allergy diagnosed by allergist) | iAGE | 24 months | 5% total protein intake/day | DBPCFC (4.3 g MP): OIT vs. placebo: T1 (8 months); 73 vs. 57% T3 (24 months): 82 vs. 71% | AE: no product related |
Reference | Design | Sample | Participants Characteristic | Form of Allergen | Duration | Maintenance Dose | Efficacy | Safety |
---|---|---|---|---|---|---|---|---|
Burks et al. (2012) [47] | Double-blind, placebo-RCT | n = 55 (5–11 y) OIT: 40 Placebo: 15 | Clinical history of egg-allergy | EWP | 24 months | 2 g EWP | At 10 and 22 months: Desensitization to 5 and 10 g of EPW: OIT: 55% and 75% Placebo: 0% and 0% (p < 0.00, p < 0.0011) At 24 months: SU to 10 g EPW + whole cooked egg: OIT: 11%, placebo: 0% (p < 0.03) | AE: % participants OIT: 78%; Placebo: 20% (p < 0.01) Severe AE: no |
Jones et al. (2016) [7] | Extension of previous study [47] at 4 y | n = 55 (5–11 y) OIT: 40 Placebo: 15 | Clinical history of egg-allergy | EWP | 2 y | 2 g EWP | SU to 10 g EPW + whole cooked egg by 3 and 4 y: OIT: 45% and 50% | AE during OIT dosing: 54% OIT participants, mostly mild symptoms |
Itoh-Nogato et al. (2018) [50] | Randomized, parallel-group, delayed-start study. 1st stage: early start group on rush OIT. 2nd stage: all participants on OIT | n = 45 (5–15 y) early start: n = 23 (received rush OIT for 3 months) late-group: n = 22 (continue egg elimination for 3 months before OIT) | positive DBPCFC to ≤500 mg dried raw EPW | EWP | 1 y | 60 g of cooked egg ~1 medium size egg or 1 g EWP | Desensitization to 1000 mg EPW after 3 months: Early star: 87% Late start: 22% (p < 0.001). | AE during first stage: Early start: 80% Late-star: 0% AE requiring adrenaline; 11.6% |
Kim et al. (2020) [48] | Extension of previous published study [47] at 5 y | n = 55 (5–11 y) OIT: 40 Placebo: 15 | Clinical history of egg-allergy, Completed previous OIT study | 1 y | Unlimited consumption all form of egg | Ingestion all form of egg: SU-OIT: 100% Desensitized OIT: 43% Non-desensitized OIT: 17% Placebo: 36% | AE: no OIT participants reported symptoms to any baked egg consumption | |
Kim et al. (2020) [6] | Open label randomized trial | n = 50 (3–36 y) BE-R: n = 27 OIT-R: n = 23. OIT-assigned (OIT-A) comparison: 39 | Negative DBPCFC to BE Positive DBPCFC to unbaked egg (1444 mg of EWP) | BE vs. EWP | 2 y | 2000 mg egg white protein | SU to 7444 mg white egg protein: BE-R = 11.1% OIT-R: 43.15% OIT-A 17.9% | AE: % participants: BE-R: 2.8% OIT-R: 3.9% OIT-A: 12.6% Severe AE: only in OIT groups |
Palosuo et al. (2021) [49] | Open-label randomized trial | n = 50 (6–17 y) OIT: 32 Control: 18 | Positive DBPCFC to heated egg white | EWP | 8 months | 1 g egg-white protein | Desensitization to 1 g of egg white protein: OIT: 44% Control: 4.8% | AE: 82% participants during build-up phase No severe reactions |
Reference | Design | Sample | Participants Characteristic | Form of Allergen | Duration | Maintenance Dose | Efficacy | Safety |
---|---|---|---|---|---|---|---|---|
Varshney et al. (2011) [56] | Double-blind placebo RCT | n = 25 (1–16 y) OIT = 16 Placebo = 9 | Clinical history of reaction to peanut (<60 min after ingestion) | Peanut flour | 1 y | 4000 mg PP ~15–16 peanuts | Desensitization to 5 g PP: OFC: 100%, placebo: 0% | AE/dose: 1.2% in OIT participants during build-up phase Epinephrine: no |
Anagnostou et al. (2014) [57] | Crossover 2-phase-RCT (STOP II) | n = 85 (7–16 y) OIT: 46 Control: 39 2.phase: Control -> OIT | Immediate reaction after peanut ingestion, positive DBPCFC | Peanut flour | 6 months | 800 mg PP | Desensitization to 1400 mg PP: First phase: OIT: 62%, control: 0% (p < 0.001) Second phase: Control after OIT: 54% | AE per OIT dose: 6.3%- mild reaction Adrenaline: 0.01% dose |
Vickery et al. (2017) [58] | Double-blind placebo RCT | n = 37 (9–36 months) Low dose (LD): 20 High dose (HD): 17 | Positive OFC to 4 g PP | Peanut-flour | 22–36 months | PP: LD: 300 mg HD: 3000 mg | SU to 5 g PP: 29/37 (78%) LD: 85%; HD: 71%, p = 0.43 Control: 4% | AE: % participants: LD: 90%, HD 100% |
Bird et al. (2017) [60] | Double-blind placebo RCT Phase 2 (ARC001) | n = 55 (4–26 y) AR101: 29 Placebo: 26 | Positive DBPCFC to 143 mg PP | AR101-comercial product | 20–34 weeks | 300 mg PP | Desensitization to 300 mg PP AR101: 79%, placebo: 19% (p < 0.001) Desensitization to 600 mg PP: AR101: 62%, placebo: 0% (p < 0.001) | AE: % participants during treatment: AR101: 93%, placebo: 46%. No severe AE |
Vickery et al. (2018) [61] | Double-blind placebo-RCT Phase 3 (PALISADE) | n = 496 (4–17 y) AR101: 372 Placebo: 124 | Positive DBPCFC to 100 mg PP (1/3 peanut) | AR101-comercial product | 1 y | 300 mg PP | Desensitization to 600 mg PP: AR101: 67.2%, placebo: 4% (p < 0.001) | AE: % participants: AR101: 98.7%, placebo: 95.2% Severe AR: AR101: 4.3%, placebo: 0.8% |
Chintrajah et al. (2019) [33] | Double-blind placebo-RCT 2 phase study Peanut-0: no peanut after OIT Peanut-300: 300 mg PP daily after OIT Placebo: received placebo (POISED study) | n = 120 (7–55 y) Peanut-0: 60 Peanut-300: 35 placebo: 25 | Positive DBPCFC to 500 mg PP | Peanut flour | 3 y | 4 mg od PP | Negative DBPCFC to 4 g PP at week 104 (desensitization) and 117 (SU): Peanut-0: 85%, 35% Peanut-300: 83%, 54% Placebo: 4%, 4% SU to 4 g PP at week 156: Peanut-0: 13 Peanut-300: 37% | AE: % participants through 1st to 3rd years: Peanut-0: 95–2% Peanut-300: 91–20% Placebo: 64–5% |
Vickery et al. (2020) [62] | Open-label follow-on study of previous study [61] (ARC004) PTAH = formerly AR101 | n = 358 (4–17 y) PTAH: 256 (A) PTAH: daily dosing: 300 mg daily (B) PTAH: non- daily dosing 300 mg (e.g., biweekly) (C) PTAH-naive: 102 | PTAH: negative DBPCFC to 300 mg PP PTAH naïve: placebo arm from PALISADE | PTAH (Palforzia commercial product) | 1–2 y | 300 mg of PTAH | Desensitization to 2 g PP Daily dosing > non-daily dosing | AE: almost all PTAH participants Daily dosing < non-daily dosing |
Jones et al. (2022) [59] | Double-blind placebo RCT (IMPACT trial) | n = 146 (12–48 months) OIT: 96 Placebo = 50 | Positive DBPCFC to 500 mg PP | Peanut flour | 160 weeks | 2000 mg PP | Desensitization to 5 g PP OIT: 71%, placebo: 2% (p < 0.0001) SU to 5 g PP: OIT: 21%, placebo: 2% (p = 0.0021) | AE: % participants: OIT: 98%, placebo: 80% Epinephrine: OIT 22%, placebo 0% |
Fernandez-Rivas et al. (2022) [63] | Open label follow-on study of previous study [62] | n = 130 (4–17 y) A: 104 (1.5 y) B: 26 (2 y) | negative DBPCFC to 300 mg PP | PTAH (Palforzia- commercial product) | 1.5–2 y | 300 mg of PTAH | DBPCFC to 2 g PP: A: 48.1%; B: 80.8% | AE: decreased throughout the intervention period in both groups |
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Turkalj, M.; Miletić Gospić, A.; Višekruna Džidić, I.; Banić, I. Food Allergen Immunotherapy in the Treatment of Patients with IgE-Mediated Food Allergy. Medicina 2024, 60, 121. https://doi.org/10.3390/medicina60010121
Turkalj M, Miletić Gospić A, Višekruna Džidić I, Banić I. Food Allergen Immunotherapy in the Treatment of Patients with IgE-Mediated Food Allergy. Medicina. 2024; 60(1):121. https://doi.org/10.3390/medicina60010121
Chicago/Turabian StyleTurkalj, Mirjana, Adrijana Miletić Gospić, Ivona Višekruna Džidić, and Ivana Banić. 2024. "Food Allergen Immunotherapy in the Treatment of Patients with IgE-Mediated Food Allergy" Medicina 60, no. 1: 121. https://doi.org/10.3390/medicina60010121