Direct Oral Penicillin PEN-FAST Challenge: Safe and Effective Approach to Assess Low-Risk Allergies to penicillin

Recent study published in JAMA Internal Medicine suggests that a direct oral penicillin challenge is a safe and efficacious method for evaluating patients with low-risk allergies to penicillin. This approach could potentially replace the conventional method of penicillin skin testing followed by an oral challenge.

The study, led by Ana Maria Copaescu, MD, from the Department of Medicine’s Division of Allergy and Clinical Immunology at McGill University Health Centre in Montreal, examined whether risk-stratified direct oral penicillin challenges were noninferior to the traditional penicillin skin testing followed by an oral challenge for patients with low-risk penicillin allergies (PEN-FAST score <3).

Key Findings and Background:

● PEN-FAST Score: The PEN-FAST clinically-validated decision rule provides point-of-care risk assessment for individuals with reported penicillin allergies. A score under 3 is associated with a low risk of allergies, with a negative predictive value of 96.3%.

● Study Design: The research employed a parallel design with two groups to determine if a direct oral penicillin challenge could be as effective as the standard protocol. The study involved six specialized centers across North America (US and Canada) and Australia and was conducted openly from June 2021 to December 2022.

● Participants: A total of 382 individuals were recruited, with 377 included in the analysis. The median age of participants was 51 years, with 65.5% of them being female. Most patients had PEN-FAST scores of 0 or 1.

● Intervention and Control Arms: Participants were randomly assigned to either the intervention arm (direct oral penicillin challenge) or the control arm (penicillin skin testing followed by an oral challenge).

● Primary Outcome: The primary outcome of the study was the confirmation of a positive immune-mediated oral challenge by a clinician within one hour following the intervention.

● Results: Only one participant in each arm experienced the primary outcome. The risk difference was 0.0084 percentage points with a 90% confidence interval (CI) ranging from -1.22 to 1.24 points, demonstrating noninferiority.

● Adverse Events: During the five-day follow-up after the oral challenge, there were a total of 9 immune-mediated adverse events in the intervention arm and 10 in the control arm, with no serious adverse events reported.

The study's findings suggest that a direct oral penicillin challenge is a less resource-intensive, cost-effective, and scalable approach for assessing low-risk, unverified penicillin allergies. This method could potentially be implemented in various treatment settings, reducing the need for specialist allergy evaluations and providing a more accessible option for patients.

Reference:

Copaescu AM, Vogrin S, James F, et al. Efficacy of a Clinical Decision Rule to Enable Direct Oral Challenge in Patients With Low-Risk Penicillin Allergy: The PALACE Randomized Clinical Trial. JAMA Intern Med. 2023;183(9):944–952. doi:10.1001/jamainternmed.2023.2986.