FDA report on safety and efficacy of allergen extracts

This month, Slater et al. report the conclusions from the FDA’s internal review of literature supporting the efficacy of nonstandardized allergen extracts (J Allergy Clin Immunol 2012; 129:1014-1019). The FDA commenced this review in 2003, recognizing that 20 years had passed since the last advisory panel had made recommendations. Additionally, the group used additional resources, such as a greater publication base, in order to expand the search for reliable publications, and the review included consultation of the FDA Adverse Events Reporting System (AERS).

Slater et al. present the interesting historical context for their re-evaluation, beginning with the shift of regulatory responsibility for non-standardized allergenic extracts from the NIH to the FDA in 1972. They note that the FDA convened two separate advisory panels – the first from1974 through 1979 and the second from 1982 through1983 – to recommend classifications for non-standardized allergenic extracts.. The second panel was convened to amend certain previous classification recommendations, as required by a change in the regulations framing the classification process.

The authors discuss extensively the findings of the literature review as well as the review of the current nomenclature. The FDA’s internal committee presented the following results from their review of 1269 allergen extracts:

· 480 extracts used in the diagnosis and treatment of allergic disease were addressed in the literature;

· 207 extracts for diagnostic use only were addressed in the literature;

· 565 extracts had minimal or no supportive literature; and

· 17 extracts were associated with potential safety concerns.

The authors report that almost half of the allergen extracts have little or no data that support their use as a diagnostic and/or therapeutic agent. There is, however, no evidence of product-class safety-specific issues. The committee did identify seventeen extracts as having possible safety concerns.

Acetominophen sensitivity in children with asthma linked to decreased glutathione levels

Stephenson et al. present results of their investigation into mechanisms of acetaminophen sensitivity risk in children with moderate to severe asthma in a Letter to the Editor in this issue (J Allergy Clin Immunol 2012;129:863-865.e2). Based on their previous findings of (nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription factor-associated glutathione deficiency in children with severe asthma, the authors report decreased expression of the aryl hydrocarbon receptor (AHR) and AHR nuclear translocator heterodimer genes (ARNT), which regulates toxin metabolism, after ex vivo acetaminophen exposure. Phase II toxin metabolism enzymes, such as dehydrogenases, hydrolases, and kinases were decreased in children with asthma compared to controls. Extracellular glutathione release was unaltered in children with asthma, whereas glutathione was elevated in controls after acetaminophen exposure. Stephenson et al. note that AHR/ARNT regulates Nrf2 signaling, which is consistent with their previous research results.

Preliminary evidence of bed bug allergy

An interesting Letter to the Editor in this month’s issue reports findings from a small study by Price et al (J Allergy Clin Immunol 2012;129:863-865.e2) on IgE levels in individuals that have been bitten by bed bugs. The authors developed an assay to detect specific IgE against whole bed bug (Cimex lectularius) extract as well as against a bed bug salivary protein, nitrophorin (cNP). Out of 30 subjects enrolled, greater than 50% had specific IgE to whole extract and 30% had specific IgE to both whole extract and cNP. Subjects with whole extract IgE only also had dust mite and cockroach specific IgE, which was partially cross-reactive in their assay.