Elizabeth Phillips

Rationale
Antibiotic allergy labels (AAL) to first-line antibiotics such as penicillin, cephalosporins, and trimethoprim-sulfamethoxazole, lead to the use of alternative antibiotics with inferior outcomes. For low-risk penicillin (PAL), cephalosporin (CAL), and trimethoprim-sulfamethoxazole allergy (SAL) labels, direct oral challenge (DOC) without skin testing is now standard but associated with the burden of multiple repeat visits. We aimed to improve patient convenience, adherence and delabeling efficacy through Multiple Antibiotic Allergy Evaluation Strategy (MAAES-DOC).
Methods
We evaluated the safety and efficacy of MAAES-DOC, defined as two or more first-line DOC in a single visit. From January 2020-April 2024, 421 adult patients with at least two of PAL, CAL or SAL underwent risk assessment to identify low-risk patients. DOCs were done in low-risk patients after shared decision-making with tolerance confirmed post-observation period and nursing follow-up.
Results
Of 421 patients, 103 (24.5%) qualified for MAAES-DOC (median age 58 [IQR 39–72]); 82.5% female). A total of 214 AALs underwent DOCs: 85 (39.7%) PAL, 54 (25.2%) CAL, and 75 (35%) SAL. Delabeling succeeded in 102/103 (99%); 95 (92.2%) completed in a single visit, and 7 in two, with a median of 2 labels removed per patient. In combination groups, 27/28 (96.4%) had PAL+CAL delabeled, 48/49 (97.9%) PAL+SAL, 16/18 (88.9%) CAL+ SAL, and 8/8 (100%) had all three removed.
Conclusions
MAAES-DOC is a safe and effective “real-world” approach for delabeling multiple low-risk antibiotic allergies through multiple DOC in a single visit. This strategy streamlines care by safely and efficaciously removing first-line AAL, reducing clinic visits while maintaining high success and patient adherence.

Rationale
Over one third of patients have drug allergy labels and the incidence is rising. Emerging data suggest multiple drug allergy labels may be associated with anxiety and depression. We aimed to evaluate whether anxiety or depression were associated with having multiple drug allergy labels using validated screening tools.
Methods
This cross-sectional analysis of adult patients in the United States Drug Allergy Registry (USDAR) (1/9/2019-8/4/2025) collected drug allergy labels (DALs), depression (PHQ-9) and anxiety (GAD-7) scores. We assessed the association of clinically significant depression (PHQ-9 ≥10) and anxiety (GAD-7 ≥10) with number of DALs, overall and stratified by sex.
Results
Among 2048 participants from 6 sites, 1302 (64%) had 1DAL and 746 (36%) had ≥2DALs. Majority were women (1556, 76%), white (1753, 86%) and non-Hispanic (1934, 94%). The mean age was 51±17. Clinically significant depression and anxiety were noted in 141 (7%) and 150 (7%) patients respectively. Compared to those reporting no or mild symptoms, patients with clinically significant depression were more likely to report ≥2DALs (RR 1.29, p=0.009), and those with clinically significant anxiety were more likely to ≥2DALs (RR 1.33, p=0.002). Men with clinically significant depression (RR 1.76, p=0.021) or anxiety (RR 2.28, p=<0.001) were more likely to report ≥2DALs.
Conclusions
Patients with clinically significant anxiety or depression were more likely to report multiple DALs across a multi-site prospective sample. These findings support the need to incorporate mental health screening into drug allergy evaluations.

Background: IrAEs are prevalent in patients treated with immune checkpoint inhibitors (ICI) and mimic classical autoimmune diseases. IrAE risk prediction could improve clinical decision making and patient safety for ICI-treated patients. Classical autoimmune diseases show strong associations with germline polymorphisms and with Human Leukocyte Antigen (HLA) variants, though it is unclear if these same genetic risk factors predispose to irAEs. To identify both tolerant and irAE patients, we mined Vanderbilt University Medical Center (VUMC) BioVU, a biorepository of >300K DNA samples linked to de-identified medical records and evaluated genome-wide and imputed HLA class I and II associations with irAE risk. Methods: We identified 1,472 ICI-treated BioVU subjects: 428 with ≥ 1 irAE, and 1044 with no irAEs ≤ 6 months from last ICI treatment. Genotyping was performed by Illumina MEGAEX array. Records were screened for use of irAE therapies (e.g. systemic corticosteroids, infliximab, levothyroxine) after ICI treatment, with chart adjudication. Association tests were performed using Firth’s logistic regression adjusting for age, sex, ICI regimen, and 3 principal components to assess 1) HLA Class I and II alleles; 2) HLA evolutionary divergence; and 3) GWAS to evaluate total irAEs, organ-specific irAEs, or other specific irAEs (sample size permitting). Endocrine irAEs were excluded to be presented in a separate focused study. Results: In GWAS analyses, 53 SNPs and 23 SNPs were identified significantly (nominal p ≤ 5e-8) associated with GI and neuro-toxicity, respectively. We did not identify any significant HLA class I or II associations with irAE or organ-grouped irAEs, including most evolutionary divergence association tests. We noted marginal association (FDR=0.12, OR=6.85) of rheumatic irAEs with HLA-DRB1*10:01, an HLA class II allele with RA-specific epitope motif. Patients experiencing lung irAEs were more likely to have a high HLA class I and II evolutionary divergence sum (p = 0.013 and p=0.046, respectively). Assessment of associations with specific irAEs, validation of known associations with irAEs or autoimmune disorders, including polygenic risk scores, are underway. Conclusions: We had several SNP-irAE associations, though appropriate classification schemas to maximize power and detect genetic variation remain challenging. We will soon expand with 1,800 additional ICI-treated patients (n=~3,300 in toto), creating a robust resource for irAE genetic associations.