Background
Previous studies have shown that direct oral provocation tests, without prior skin testing, in children having delayed onset, benign rashes to beta-lactam antibiotic is safe and effective. Although, this test is useful in confirming drug hypersensitivity reactions, there is no standard protocol recommendation of drug provocation tests. This study aimed to evaluate the safety of the direct oral provocation test, using the Amoxicillin-2-step-challenge without prior skin testing, in children with history of non-immediate reactions to amoxicillin.
Methods
The Amoxicillin-2-step-challenge protocol was performed in children with history of non-immediate reactions to amoxicillin. This protocol is composed of 2 doses of amoxicillin, with a 30-min interval; continued for a total of 5 days. All of the patients had not undergone skin testing before the oral provocation test.
Results
This study included 54 children, having a median age of 6.6 years, with 70.4% being male. Amoxicillin and amoxicillin-clavulanic acid were reported as the culprit drug in 75.9% and 24.1%, respectively. The index reactions were maculopapular (MP) rash in 79.6% and delayed urticarial rash/angioedema in 20.4%. Five patients (9.3%) had a reaction during the provocation test, all of these patients had delayed urticaria and were treated with oral antihistamine. However, 1 patient developed a fever alongside an MP rash. Laboratory investigation for this patient showed increased atypical lymphocytes and liver enzymes elevation.
Conclusions
Direct oral provocation tests, using the Amoxicillin-2-step-challenge, without prior skin testing, revealed good, immediate safety for the diagnosis of amoxicillin hypersensitivity in children with history of non-immediate reactions to amoxicillin.
RATIONALE: A SCIT that is both efficacious and ultra-short course in its administration is an ideal therapy for allergic rhinoconjunctivitis. This combination facilitates adherence, but must not compromise safety. In this study, PQ Birch was increased up to 5.5 fold and investigated with respect to dose-response and adverse events. This is a SCIT with a purified allergen extract, chemically modified to produce an allergoid. It is adsorbed to microcrystalline tyrosine (MCT) and MPLÒ, a TLR-4 agonist as an adjuvant. METHODS: Dose regimens of 5100, 15300, 20100, 27300 SU and placebo were compared using conjunctival provocation test (CPT). All doses were administered by weekly injection over 6 to 8 weeks. 370 patients were treated in 28 sites in Germany and Austria. The primary efficacy analysis was performed on a modified full analysis set. The MCP-Mod methodology (multiple comparison proceduremodelling) tested for a dose-response to describe the shape of the curve. RESULTS: A statistically significant dose-response (p<0.01) was shown, which approached a plateau with the 27300 SU dose. The median effective dose (ED50) was 2600 SU. Systemic reactions were seen in 2.0% (20100 SU group) up to 15.1% (5000 SU group) and in 11.3% of patients in Placebo. Most were mild and all were short-lived. CONCLUSIONS: The 27300 SU dose will be taken into phase III having achieved an increase in efficacy of 50% without incurring a different pattern of adverse events than the lower doses.
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