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Evaluating the relationship between antidrug antibodies and infusion-related reactions/safety outcomes in patients with Fabry disease receiving enzyme replacement therapy (ERT): A systematic literature review
Abstract   Peer reviewed

Evaluating the relationship between antidrug antibodies and infusion-related reactions/safety outcomes in patients with Fabry disease receiving enzyme replacement therapy (ERT): A systematic literature review

Patricio Aguiar, Derralynn Hughes and John Bernat
Molecular genetics and metabolism, Vol.147(2), 109302
02/2026
DOI: 10.1016/j.ymgme.2025.109302

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Abstract

The impact of antidrug antibodies (ADAs) on safety/tolerability outcomes in patients with Fabry disease (FD) receiving ERTs is not well understood. A systematic literature review was conducted to assess this relationship. Literature searches were conducted in MEDLINE and Embase up to 4-March-2025. Eligible studies reported on the relationship between ADA status and infusion-related reactions (IRRs) and/or safety outcomes in patients with FD receiving ERT. Nine (of 615 screened) publications reported IRRs and/or adverse events (AEs) by ADA status in patients with FD receiving ERT: one randomized controlled trial (RCT) and eight non-randomized studies (NRS). Four studies (RCT: n = 1; NRS: n = 3) reported proportions of patients with ADAs at baseline (range: 7-35 %). Six studies (1 RCT, 5 NRS) reported IRRs by ADA status. Across these studies, the sample-size weighted mean proportion of patients with IRRs was 38 % (range: 24-90 %) in the pooled ADA-positive population (n = 637), compared with 18 % (range: 0-39 %) in the ADA-negative population (n = 682). Three of these studies, plus an additional three studies (n = 6; all NRS), evaluated associations between ADAs and IRRs; four reported statistically significant positive associations and two reported no significant associations. Two NRS assessed severe IRRs and reported significant associations with ADA-positivity (p = 0.033 and p < 0.01). One NRS evaluated any AEs and serious AEs, reporting significant associations with ADA-positivity. Two NRS assessed hypersensitivity reactions (HRs); one reported significantly more HRs and severe HRs in patients with versus without ADAs (HRs: 44 % vs 5 %, p < 0.001; severe HRs: 5 % vs 0 %; p = 0.025) while the other reported no significant association. Most studies reported a positive association between ADA-positivity and increased risk of IRRs/AEs. The interpretation of these findings is limited by small sizes, retrospective study designs, variability in ADA assessment methods/timing, prior ERT exposure, and differences in safety and tolerability outcomes. Additional studies using standardized ADA testing are needed.

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