PMID- 37488580 OWN - NLM STAT- MEDLINE DCOM- 20230807 LR - 20230807 IS - 1750-1172 (Electronic) IS - 1750-1172 (Linking) VI - 18 IP - 1 DP - 2023 Jul 24 TI - Safety and tolerability of agalsidase beta infusions shorter than 90 min in patients with Fabry disease: post-hoc analysis of a Japanese post-marketing study. PG - 209 LID - 10.1186/s13023-023-02803-5 [doi] LID - 209 AB - BACKGROUND: Agalsidase beta, an enzyme replacement therapy for Fabry disease, is dosed biweekly at 1 mg/kg body weight, with increasing infusion rates based on tolerability. The US label specifies >/= 90-min infusions for all patients; the US and EU labels require /= 90 min). SAEs were rare (0.6%), and the frequency of all safety events decreased over the treatment course. Little impact of infusion duration on safety outcomes was observed: IARs and AEs were numerically more common when infusion duration was >/= 90 min compared to < 90 min (IARs: 2.0% vs 0.9%; AEs: 2.9% vs 1.4%), while the rate of SAEs was similar (0.4% vs 0.5%). IAR, AE, and SAE frequencies decreased significantly with increasing infusion rates, and this trend was consistent in patients < 30 kg. Safety events tended to be less frequent in patients < 30 kg vs those >/= 30 kg (IARs: 1.8% vs 2.1%; AEs: 2.3% vs 3.6%; SAEs: 0.0% vs 0.6%), although the differences were not statistically significant. IARs occurred in < 1% of all infusions in the < 30 kg group, 84% of which were < 90 min. More anti-agalsidase beta antibody-positive patients experienced IARs (41.9% vs 30.7%; P = 0.0445) and AEs (61.1% vs 49.3%; P = 0.0497) vs antibody-negative patients; however, there was no significant difference in the frequency of SAEs. In patients with available data, no changes in antibody status were observed after infusion durations were reduced to < 90 min. CONCLUSIONS: The results of this post-hoc analysis demonstrated no significant impact of infusion duration on safety outcomes, and no significant difference in outcomes between patients of different weights. These findings suggest that infusion times in patients who are tolerating treatment can, with careful monitoring, be gradually decreased. CI - (c) 2023. The Author(s). FAU - Lee, Chae Sung AU - Lee CS AUID- ORCID: 0000-0003-2853-2896 AD - Sanofi, 450 Water Street, Cambridge, MA, 02141, USA. chase.lee@sanofi.com. FAU - Tsurumi, Mina AU - Tsurumi M AD - Sanofi K. K., Tokyo, Japan. FAU - Eto, Yoshikatsu AU - Eto Y AD - Advanced Clinical Research Center, Southern Tohoku Research Center for Neuroscience, Kanagawa, Japan. LA - eng SI - ClinicalTrials.gov/NCT00233870 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230724 PL - England TA - Orphanet J Rare Dis JT - Orphanet journal of rare diseases JID - 101266602 RN - EC 3.2.1.22 (alpha-Galactosidase) RN - 0 (Antibodies) SB - IM MH - Humans MH - alpha-Galactosidase/administration & dosage/adverse effects/therapeutic use MH - Antibodies MH - East Asian People MH - *Fabry Disease/drug therapy MH - Treatment Outcome MH - Enzyme Replacement Therapy PMC - PMC10367408 OTO - NOTNLM OT - Agalsidase beta OT - Enzyme replacement therapy OT - Fabry disease OT - Infusion time OT - Infusion-associated reaction COIS- Chae Sung Lee and Mina Tsurumi are employed by Sanofi. Yoshikatsu Eto is a paid consultant to Sanofi. EDAT- 2023/07/25 01:09 MHDA- 2023/07/27 06:42 PMCR- 2023/07/24 CRDT- 2023/07/24 23:45 PHST- 2023/02/09 00:00 [received] PHST- 2023/07/05 00:00 [accepted] PHST- 2023/07/27 06:42 [medline] PHST- 2023/07/25 01:09 [pubmed] PHST- 2023/07/24 23:45 [entrez] PHST- 2023/07/24 00:00 [pmc-release] AID - 10.1186/s13023-023-02803-5 [pii] AID - 2803 [pii] AID - 10.1186/s13023-023-02803-5 [doi] PST - epublish SO - Orphanet J Rare Dis. 2023 Jul 24;18(1):209. doi: 10.1186/s13023-023-02803-5.