Allergy treatment

Abstract

The present invention concerns a method of treating peanut allergy in a subject, or a population of subjects, the method comprising administering to said subject or population of subjects a peanut allergen by an oral immunotherapy (OIT) regimen comprising a dose escalation phase in which the peanut allergen is administered in a dose which is increased in increments from an initial dose of the allergen equivalent of 5 mg peanut protein or less to a dose of the allergen equivalent of 200 mg peanut protein or more within 4 to 9 weeks from the administration of the initial dose. The treatment reduces the length of the build-up phase in peanut OIT methods and improves the likelihood or odds of the subject achieving sustained unresponsiveness.

1 . A method of treating peanut allergy in a subject, the method comprising administering to said subject a peanut allergen by an oral immunotherapy regimen comprising a dose escalation phase, wherein the peanut allergen is administered in a dose which is increased in increments from an initial dose of the allergen equivalent of 5 mg peanut protein or less, preferably an initial dose of the allergen equivalent of 2 mg peanut protein or less, to a dose of the allergen equivalent of 200 mg peanut protein or more within 4 to 9 weeks from administration of the initial dose. 
     
     
         2 . The method of  claim 1 , wherein during said dose escalation phase the peanut allergen dose is increased in increments to
 (i) a dose of the allergen equivalent of 400 mg peanut protein or more within 6 to 11 weeks from administration of the initial dose, and/or   (ii) a dose of the allergen equivalent of 800 mg peanut protein or more within 8 to 13 weeks from administration of the initial dose, and/or   (iii) a dose of the allergen equivalent of 2 g peanut protein or more within 16 to 24 weeks from administration of the initial dose.   
     
     
         3 . The method of  claim 1 , wherein the dose escalation phase comprises a series of roughly doubling dose increments from the initial dose to the dose of 200 mg, 400 mg, 800 mg, 2 g or more. 
     
     
         4 . The method of  claim 1 , wherein the dose escalation phase is 8 to 24 weeks and a final dose is reached at the end of the dose escalation phase. 
     
     
         5 . The method of  claim 1 , to wherein a final dose is reached at the end of the dose escalation phase and said treatment further comprises a maintenance phase following completion of the dose escalation phase, in which the peanut allergen is administered at a set maintenance dose which is ±10% of the final dose reached at the end of the dose escalation phase,
 preferably wherein 
 (i) the maintenance dose is the allergen equivalent of at least 200 mg, preferably at least 400 mg, preferably at least 800 mg, particularly preferably at least 2 g, especially preferably about 200 mg, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, 4000, 4100 or 4200 mg peanut protein, and/or 
 (ii) the duration of the maintenance phase is 2 weeks or more following the completion of the dose escalation phase, preferably wherein the duration of the maintenance phase is 20-104 weeks. 
 
     
     
         6 . The method of  claim 1 , wherein:
 the peanut allergen dose is administered at least every 3 days, preferably every 2 days during the dose escalation and/or maintenance phase, preferably wherein the peanut allergen dose is administered every day.   
     
     
         7 . The method of  claim 1 , wherein the dose escalation phase comprises a rush phase in which the peanut allergen is administered in a dose which is increased in increments from the initial dose to a dose of the allergen equivalent of 12 mg peanut protein or more within 1 hour to 1 week from administration of the initial dose, preferably wherein the rush phase is completed in 1 to 12 hours from administration of the initial dose. 
     
     
         8 . The method of  claim 1 , wherein
 (i) the peanut allergen is, or is present in, or derived from, a peanut protein, and/or   (ii) the peanut allergen is provided as peanut protein, preferably as peanut flour or a defatted form thereof, and/or   (iii) the peanut allergen is one or more of Ara h1 to Ara h9 or a modified form thereof, preferably one or more of Ara h1, h2, h3, h6, h8 or h9, preferably Ara h2 or is a modified form thereof.   
     
     
         9 . The method of  claim 1 , wherein the peanut allergen is administered in or on apple sauce, pudding, yoghurt or chocolate. 
     
     
         10 . The method of  claim 1 , wherein the subject is less than 18 years old, preferably less than 10 years old, preferably less than 5 years old, wherein the subject is from 1 month to 12 years old, preferably wherein the subject is less than 6 years old or from 6 to 12 years old or 1 to 5 years old. 
     
     
         11 . The method of  claim 1 , wherein reducing time to reach maintenance dose compared to time taken to reach a maintenance dose in an oral immunotherapy regimen using a longer dose escalation phase to reach a same maintenance dose improves the likelihood or the odds of the subject achieving sustained unresponsiveness, wherein preferably reaching the maintenance dose in 8 to 24 weeks improves the likelihood or the odds of the subject achieving sustained unresponsiveness compared to oral immunotherapy regimens using a longer dose escalation phase to reach the same maintenance dose. 
     
     
         12 . A method of treating peanut allergy in a population of subjects, the method comprising administering to a populations of subjects a peanut allergen by an oral immunotherapy regimen comprising a dose escalation phase in which the peanut allergen is administered in a dose which is increased in increments from an initial dose of the allergen equivalent of 5 mg peanut protein or less to a dose of the allergen equivalent of 200 mg peanut protein or more within 4 to 9 weeks from administration of the initial dose and wherein preferably said peanut allergen, subject and/or oral immunotherapy regimen is as defined in  claim 1 , preferably wherein:
 a) said dose escalation from the allergen equivalent of 5 mg peanut protein or less to the allergen equivalent of 200 mg peanut protein or more is achieved within 4 to 9 weeks from administration of the initial dose in more than 75% of the population; or   b) the median time to achieve said dose escalation from the allergen equivalent of 5 mg peanut protein or less to the allergen equivalent of 200 mg peanut protein or more is 4 to 9 weeks from administration of the initial dose.   
     
     
         13 . The method of  claim 1  or  claim 12  further comprising administration of a probiotic orally at least once every week during said peanut dose escalation phase, preferably at a dose of 1×10 8  cfu to 2×10 10  cfu. 
     
     
         14 . The method of  claim 13  wherein the probiotic is administered at least every three days, preferably wherein the probiotic is to be administered daily. 
     
     
         15 . The method of  claim 14 , wherein the dose escalation phase comprises a rush phase in which the peanut allergen is administered in a dose which is increased in increments from the initial dose to a dose of the allergen equivalent of 12 mg peanut protein or more within 1 hour to 1 week from administration of the initial dose, preferably wherein the rush phase is completed in 1 to 12 hours from administration of the initial dose, wherein the probiotic is administered at least once during the rush phase and at least once every week thereafter, preferably at a dose of 1×10 8  cfu to 2×10 10  cfu. 
     
     
         16 . The method of  claim 13 , wherein the probiotic is capable of inducing an increased number of tolerogenic dendritic cells after in vivo administration, preferably wherein the tolerogenic dendritic cells are plasmacytoid dendritic cells (pDCs). 
     
     
         17 . The method of  claim 13 , wherein the probiotic is a species of  Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Escherichia  or  Bacillus , preferably wherein
 i) the probiotic is a species of  Lactobacillus , selected from the list of  Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus johnsonii, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus salivarius  and  Lactobacillus helveticus , preferably wherein the probiotic is  Lactobacillus rhamnosus , or   ii) the probiotic is  Lactobacillus rhamnosus  GG,  Bifidobacterium lactis, Saccharomyces boulardii, Escherichia coli  Nissle 1917,  Streptococcus thermophilus  or  Bifidobacterium breve.      
     
     
         18 . The method of  claim 13 , wherein for each administration of peanut allergen, the probiotic and peanut allergen are administered simultaneously, separately or sequentially, preferably simultaneously in a single or separate compositions, preferably wherein for each administration of peanut allergen, the peanut allergen is administered one minute, two minutes, three minutes, four minutes, five minutes, ten minutes, 30 minutes, 1 hour, or 2 hours or more up to 12 hours before the probiotic, or, the probiotic is administered one minute, two minutes, three minutes, four minutes, five minutes or ten minutes, 30 minutes, 1 hour, or 2 hours or more up to 12 hours before the peanut allergen. 
     
     
         19 . The method of  claim 13 , wherein for each administration of peanut allergen, the peanut allergen and probiotic are administered separately up to 7 days apart, preferably up to 1, 2, 3, 4, 5 or 6 days apart. 
     
     
         20 . The method of  claim 13 , wherein the probiotic is administered in water, cow's milk, soy milk, or other milk or drink.