Infusion-related reactions in donanemab-treated participants with early symptomatic Alzheimer's disease.

INTRODUCTION: Infusion-related reactions (IRRs) and hypersensitivity are adverse events associated with therapeutic antibodies. Characterization of IRRs can lead to improved risk anticipation and management of this event. This post hoc analysis characterizes IRRs in donanemab-treated participants with early symptomatic Alzheimer's disease (AD) from several multicenter studies. METHODS: Data were pooled from the donanemab-treated population from TRAILBLAZER-ALZ, TRAILBLAZER-ALZ 2, a stand-alone open-label addendum to TRAILBLAZER-ALZ 2, TRAILBLAZER-EXT, and TRAILBLAZER-ALZ 4. Descriptive statistics were used to characterize IRRs and related events. A random forest model identified potential association between IRRs and 40 baseline variables. RESULTS: Of 2727 donanemab-treated participants, 225 (8.3%) reported IRRs. Of 216 participants with immediate events, 122 (56.5%) were mild and 83 (38.4%) were moderate. Thirteen (0.5%) participants reported a serious event. Of IRRs occurring on the day of infusion, 87.8% occurred during or within 30 min after infusion. Of donanemab-treated participants with IRRs, 194 (77.0%) reported their first IRR by the fourth infusion. The most common symptoms reported within 24 h of infusion were nausea/vomiting (3.5%), chills (3.3%), and erythema (3.1%). In an exploratory analysis, 11/29 (37.9%) participants with at least one laboratory value taken after IRR and related events, as well as a corresponding baseline value, had elevated tryptase levels after IRR; events were of moderate severity in 82% of these participants versus 44% of those without tryptase elevations. Of donanemab-treated participants who previously experienced an IRR, 164 (65.1%) received a rechallenge infusion. Prophylaxis medication (primarily antihistamines) was used at rechallenge in 38 (23.2%) of rechallenged participants but did not reduce IRR risk. Machine learning models identified previous drug allergy and previous anaphylaxis as significant predictors of IRRs (p < 0.01 for both). DISCUSSION: IRRs are a common occurrence with donanemab treatment. The majority of IRRs among donanemab-treated participants were mild to moderate, and rechallenge was often tolerated. Serious IRRs and anaphylaxis were reported.Trial Registration: NCT03367403; NCT04437511, NCT04640077, NCT05108922.