German cockroach subcutaneous immunotherapy: Impact on nasal responses and allergen-specific immunity among urban children with asthma
Background: Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children.Objective: To determine if nasal allergen challenge (NAC) responses to cockroach allergen would improve following one year of SCIT.Methods: Urban children with asthma, cockroach-sensitized (skin prick test [SPT] and serum specific IgE) and reactive on NAC, participated in a yearlong randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean total nasal symptoms scores (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, SPT wheal size, serum allergen-specific antibody production and T-cell responses to cockroach allergen were assessed.Results: Changes in mean NAC TNSS did not differ between SCIT-assigned (n=28) versus placebo-assigned (n=29) participants (p=0.63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach sIgE decreased to a similar extent in both groups, while decreased cockroach SPT wheal size was greater among SCIT participants (p=0.04). A 200-fold increase in cockroach sIgG4 was observed among subjects receiving SCIT (p<0.001) but was unchanged in the placebo group. T-cell interleukin-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (p=0.002), while no effect was observed for interleukin-10 or interferon-gamma.Conclusion: A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum sIgG4 production and down-modulation of allergen stimulated T-cell responses. Overall design: CRITICAL (ClinicalTrials.gov NCT03541187) was a randomized, double-blind, placebo-controlled, multicenter trial of non-standardized aqueous glycerinated German cockroach (Blattella germanica) allergenic extract (Stallergenes Greer USA, Lenoir, NC) or placebo administered by subcutaneous injection completed between July 2018 and June 2022. Children ages 8-17 years, with persistent asthma for at least one year and living in low income areas of 10 large US cities were eligible if sensitized to German cockroach extract by both prick skin test and cockroach-specific IgE = 0.35 kUA/L. A positive graded cockroach NAC, defined as either a Total Nasal Symptom Score (TNSS) = 6 on a 12-point scale or a TNSS sneeze score of 3, was also required.Key exclusion criteria included National Asthma Education and Prevention Program classification of severe persistent asthma at randomization; AIT in the last year or anti-IgE, anti-IL-4R-alpha, anti-IL-5/IL5R therapy within six months of the NAC procedure; nasal polyposis or structural nasal abnormalities; a history of anaphylaxis grade 3 or higher; more than 2 courses of systemic corticosteroids within the 12 months or one course within the last 3 months prior to enrollment; or medication use or medical conditions potentially posing additional risk.