Safety and feasibility of oral immunotherapy to multiple allergens for food allergy

Philippe Bégin, Lisa C Winterroth, Tina Dominguez, Shruti P Wilson, Liane Bacal, Anjuli Mehrotra, Bethany Kausch, Anthony Trela, Elisabeth Hoyte, Gerri O'Riordan, Scott Seki, Alanna Blakemore, Margie Woch, Robert G Hamilton, Kari C Nadeau, Philippe Bégin, Lisa C Winterroth, Tina Dominguez, Shruti P Wilson, Liane Bacal, Anjuli Mehrotra, Bethany Kausch, Anthony Trela, Elisabeth Hoyte, Gerri O'Riordan, Scott Seki, Alanna Blakemore, Margie Woch, Robert G Hamilton, Kari C Nadeau

Abstract

Background: Thirty percent of children with food allergy are allergic to more than one food. Previous studies on oral immunotherapy (OIT) for food allergy have focused on the administration of a single allergen at the time. This study aimed at evaluating the safety of a modified OIT protocol using multiple foods at one time.

Methods: Participants underwent double-blind placebo-controlled food challenges (DBPCFC) up to a cumulative dose of 182 mg of food protein to peanut followed by other nuts, sesame, dairy or egg. Those meeting inclusion criteria for peanut only were started on single-allergen OIT while those with additional allergies had up to 5 foods included in their OIT mix. Reactions during dose escalations and home dosing were recorded in a symptom diary.

Results: Forty participants met inclusion criteria on peanut DBPCFC. Of these, 15 were mono-allergic to peanut and 25 had additional food allergies. Rates of reaction per dose did not differ significantly between the two groups (median of 3.3% and 3.7% in multi and single OIT group, respectively; p = .31). In both groups, most reactions were mild but two severe reactions requiring epinephrine occurred in each group. Dose escalations progressed similarly in both groups although, per protocol design, those on multiple food took longer to reach equivalent doses per food (median +4 mo.; p < .0001).

Conclusions: Preliminary data show oral immunotherapy using multiple food allergens simultaneously to be feasible and relatively safe when performed in a hospital setting with trained personnel. Additional, larger, randomized studies are required to continue to test safety and efficacy of multi-OIT.

Trial registration: Clinicaltrial.gov NCT01490177.

Figures

Figure 1
Figure 1
OIT trial design including (A) screening and trial flow chart and (B) immunotherapy protocol timeline. Amount of maintenance dose depends on number of allergen in mix (4000 mg per allergen).
Figure 2
Figure 2
Symptom occurrence with (A) initial escalation day, (B) dose escalations and (C) home dosing during OIT to multiple foods.
Figure 3
Figure 3
Kaplan-Meier curves showing time to dose of 300 mg (A), 1000 mg (B), and 4000 mg (C) per allergen in mix. Panel D shows time to reach the dose corresponding to a 10 fold increase from the threshold at which the patient reacted to peanut on initial DBPCFC. P-values from χ2 analysis were calculated using Breslow method.
Figure 4
Figure 4
Comparison of peanut-specific IgE (A) and IgG4 (B) at baseline and after one year of OIT. *p = 0.001; **p = 0.008.

References

    1. Muraro A, Roberts G, Clark A, Eigenmann PA, Halken S, Lack G, Moneret-Vautrin A, Niggemann B, Rance F. The management of anaphylaxis in childhood: position paper of the European academy of allergology and clinical immunology. Allergy. 2007;62(8):857–871. doi: 10.1111/j.1398-9995.2007.01421.x.
    1. Hompes S, Kohli A, Nemat K, Scherer K, Lange L, Rueff F, Rietschel E, Reese T, Szepfalusi Z, Schwerk N. et al.Provoking allergens and treatment of anaphylaxis in children and adolescents–data from the anaphylaxis registry of German-speaking countries. Pediatr Allergy Immunol. 2011;22(6):568–574. doi: 10.1111/j.1399-3038.2011.01154.x.
    1. Huang F, Chawla K, Jarvinen KM, Nowak-Wegrzyn A. Anaphylaxis in a New York city pediatric emergency department: triggers, treatments, and outcomes. J Allergy Clin Immunol. 2012;129(1):162–168. doi: 10.1016/j.jaci.2011.09.018. e161-163.
    1. Fleischer DM, Perry TT, Atkins D, Wood RA, Burks AW, Jones SM, Henning AK, Stablein D, Sampson HA, Sicherer SH. Allergic reactions to foods in preschool-aged children in a prospective observational food allergy study. Pediatrics. 2012;130(1):e25–e32. doi: 10.1542/peds.2011-1762.
    1. Pajno GB, Caminiti L, Ruggeri P, De Luca R, Vita D, La Rosa M, Passalacqua G. Oral immunotherapy for cow’s milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study. Ann Allergy Asthma Immunol. 2010;105(5):376–381. doi: 10.1016/j.anai.2010.03.015.
    1. de Boissieu D, Dupont C. Sublingual immunotherapy for cow’s milk protein allergy: a preliminary report. Allergy. 2006;61(10):1238–1239. doi: 10.1111/j.1398-9995.2006.01196.x.
    1. Longo G, Barbi E, Berti I, Meneghetti R, Pittalis A, Ronfani L, Ventura A. Specific oral tolerance induction in children with very severe cow’s milk-induced reactions. J Allergy Clin Immunol. 2008;121(2):343–347. doi: 10.1016/j.jaci.2007.10.029.
    1. Skripak JM, Nash SD, Rowley H, Brereton NH, Oh S, Hamilton RG, Matsui EC, Burks AW, Wood RA. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow’s milk allergy. J Allergy Clin Immunol. 2008;122(6):1154–1160. doi: 10.1016/j.jaci.2008.09.030.
    1. Meglio P, Bartone E, Plantamura M, Arabito E, Giampietro PG. A protocol for oral desensitization in children with IgE-mediated cow’s milk allergy. Allergy. 2004;59(9):980–987. doi: 10.1111/j.1398-9995.2004.00542.x.
    1. Fisher HR, du Toit G, Lack G. Specific oral tolerance induction in food allergic children: is oral desensitisation more effective than allergen avoidance?: a meta-analysis of published RCTs. Arch Dis Child. 2011;96(3):259–264. doi: 10.1136/adc.2009.172460.
    1. Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy. 2007;62(11):1261–1269. doi: 10.1111/j.1398-9995.2007.01501.x.
    1. Dello Iacono I, Tripodi S, Calvani M, Panetta V, Verga MC, Miceli Sopo S. Specific oral tolerance induction with raw hen’s egg in children with very severe egg allergy: a randomized controlled trial. Pediatr Allergy Immunol. 2013;24(1):66–74. doi: 10.1111/j.1399-3038.2012.01349.x.
    1. Burks AW, Jones SM, Wood RA, Fleischer DM, Sicherer SH, Lindblad RW, Stablein D, Henning AK, Vickery BP, Liu AH. et al.Oral immunotherapy for treatment of egg allergy in children. N Engl J Med. 2012;367(3):233–243. doi: 10.1056/NEJMoa1200435.
    1. Garcia Rodriguez R, Urra JM, Feo-Brito F, Galindo PA, Borja J, Gomez E, Lara P, Guerra F. Oral rush desensitization to egg: efficacy and safety. Clin Exp Allergy. 2011;41(9):1289–1296. doi: 10.1111/j.1365-2222.2011.03722.x.
    1. Hofmann AM, Scurlock AM, Jones SM, Palmer KP, Lokhnygina Y, Steele PH, Kamilaris J, Burks AW. Safety of a peanut oral immunotherapy protocol in children with peanut allergy. J Allergy Clin Immunol. 2009;124(2):286–291. doi: 10.1016/j.jaci.2009.03.045. 291 e281-286.
    1. Blumchen K, Ulbricht H, Staden U, Dobberstein K, Beschorner J, de Oliveira LC, Shreffler WG, Sampson HA, Niggemann B, Wahn U. et al.Oral peanut immunotherapy in children with peanut anaphylaxis. J Allergy Clin Immunol. 2010;126(1):83–91. doi: 10.1016/j.jaci.2010.04.030. e81.
    1. Clark AT, Islam S, King Y, Deighton J, Anagnostou K, Ewan PW. Successful oral tolerance induction in severe peanut allergy. Allergy. 2009;64(8):1218–1220. doi: 10.1111/j.1398-9995.2009.01982.x.
    1. Jones SM, Pons L, Roberts JL, Scurlock AM, Perry TT, Kulis M, Shreffler WG, Steele P, Henry KA, Adair M. et al.Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. 2009;124(2):292–300. doi: 10.1016/j.jaci.2009.05.022. 300 e291-297.
    1. Yu GP, Weldon B, Neale-May S, Nadeau KC. The safety of peanut oral immunotherapy in peanut-allergic subjects in a single-center trial. Int Arch Allergy Immunol. 2012;159(2):179–182. doi: 10.1159/000336391.
    1. Fleischer DM, Burks AW, Vickery BP, Scurlock AM, Wood RA, Jones SM, Sicherer SH, Liu AH, Stablein D, Henning AK. et al.Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial. J Allergy Clin Immunol. 2013;131(1):119–127. doi: 10.1016/j.jaci.2012.11.011. e111-117.
    1. Enrique E, Pineda F, Malek T, Bartra J, Basagana M, Tella R, Castello JV, Alonso R, de Mateo JA, Cerda-Trias T. et al.Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. J Allergy Clin Immunol. 2005;116(5):1073–1079. doi: 10.1016/j.jaci.2005.08.027.
    1. Gupta RS, Springston EE, Warrier MR, Smith B, Kumar R, Pongracic J, Holl JL. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011;128(1):e9–e17. doi: 10.1542/peds.2011-0204.
    1. Wang J, Visness CM, Sampson HA. Food allergen sensitization in inner-city children with asthma. J Allergy Clin Immunol. 2005;115(5):1076–1080. doi: 10.1016/j.jaci.2005.02.014.
    1. Wang J. Management of the patient with multiple food allergies. Curr Allergy Asthma Rep. 2010;10(4):271–277. doi: 10.1007/s11882-010-0116-0.
    1. Park JH, Ahn SS, Sicherer SH. Prevalence of allergy to multiple versus single foods in a pediatric food allergy referral practice. J Allergy Clin Immunol. 2010;125:AB216. doi: 10.1016/j.jaci.2009.07.002.
    1. Sicherer SH, Noone SA, Munoz-Furlong A. The impact of childhood food allergy on quality of life. Ann Allergy Asthma Immunol. 2001;87(6):461–464. doi: 10.1016/S1081-1206(10)62258-2.
    1. Christie L, Hine RJ, Parker JG, Burks W. Food allergies in children affect nutrient intake and growth. J Am Diet Assoc. 2002;102(11):1648–1651. doi: 10.1016/S0002-8223(02)90351-2.
    1. Savage JH, Matsui EC, Skripak JM, Wood RA. The natural history of egg allergy. J Allergy Clin Immunol. 2007;120(6):1413–1417. doi: 10.1016/j.jaci.2007.09.040.
    1. MacGlashan DW Jr. IgE-dependent signaling as a therapeutic target for allergies. Trends Pharmacol Sci. 2012;33(9):502–509. doi: 10.1016/j.tips.2012.06.002.
    1. Bock SA, Sampson HA, Atkins FM, Zeiger RS, Lehrer S, Sachs M, Bush RK, Metcalfe DD. Double-blind, placebo-controlled food challenge (DBPCFC) as an office procedure: a manual. J Allergy Clin Immunol. 1988;82(6):986–997. doi: 10.1016/0091-6749(88)90135-2.
    1. Calderon MA, Gerth Van Wijk R, Eichler I, Matricardi PM, Varga EM, Kopp MV, Eng P, Niggemann B, Nieto A, Valovirta E. et al.Perspectives on allergen-specific immunotherapy in childhood: an EAACI position statement. Pediatr Allergy Immunol. 2012;23(4):300–306. doi: 10.1111/j.1399-3038.2012.01313.x.
    1. Varshney P, Jones SM, Scurlock AM, Perry TT, Kemper A, Steele P, Hiegel A, Kamilaris J, Carlisle S, Yue X. et al.A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol. 2011;127(3):654–660. doi: 10.1016/j.jaci.2010.12.1111.
    1. Johannsen H, Nolan R, Pascoe EM, Cuthbert P, Noble V, Corderoy T. et al.Skin prick testing and peanut-specific IgE can predict peanut challenge outcomes in preschool children with peanut sensitization. Clin Exp Allergy. 2011;41(7):994–1000. doi: 10.1111/j.1365-2222.2011.03717.x.
    1. Simons FE, Ardusso LR, Bilò MB, Dimov V, Ebisawa M, El-Gamal YM. et al.2012 update: world allergy organization guidelines for the assessment and management of anaphylaxis. Curr Opin Allergy clin Immunol. 2012;12(4):389–399. doi: 10.1097/ACI.0b013e328355b7e4.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe