Trofinetide Use and Treatment Patterns Among Children Aged 2-4 Years with Rett Syndrome in the United States: A...

Rett syndrome (RTT) is a rare, X-linked neurodevelopmental disorder that primarily affects females. Trofinetide (TROF) was approved for RTT in individuals aged ≥2 years. Although the DAFFODIL trial examined TROF efficacy in children aged 2-4 years, real-world evidence in this age group remains limited.

A retrospective cohort study was conducted using linked medical and pharmacy claims from 01/01/2021-09/30/2024 (study period). Individuals aged 2-4 years with RTT who initiated TROF during 04/01/2023-03/31/2024 (identification period) were included (index date=first TROF RX). Outcomes included baseline characteristics, prescriber specialty, TROF persistence (≤90-day allowable gap), dosing patterns based on shipped/dispensed RXs (BID, mg; % target daily dose [%TDD]), time on treatment, and restarts among non-persistent individuals. Variables were summarized descriptively. Kaplan-Meier analyses assessed the time to treatment non-persistence.

Among 159 individuals, 65.4% were persistent and 34.6% were non-persistent; 14.5% of non-persistent individuals restarted TROF. Mean±SD age was 3.2±0.8 vs 3.3±0.7 years in persistent vs non-persistent groups. Females comprised 95.2% vs 87.3%, respectively. Child neurology was the most common prescriber specialty (54.8% vs 63.6%). Non-persistent individuals had higher rates of dysphagia (34.5% vs 16.3%), gastrostomy (20.0% vs 3.8%), and breathing irregularities (16.4% vs 1.9%). Mean BID dose and %TDD were similar between groups across shipments. Median (IQR) time on treatment was 13.3 (6.1-17.2) months in the persistent group vs 4.4 (0.8-12.6) months in the non-persistent group. Kaplan-Meier analysis showed >87.5% remained on TROF beyond 3 months and >65.0% remained on TROF through end of available follow-up.

In routine US practice, approximately two-thirds of children aged 2-4 years initiating TROF remained persistent during available follow-up, with sustained use beyond 1 year and a subset (14.5% of non-persistent children) restarting after discontinuation. Non-persistent children had significantly higher baseline rates of dysphagia, gastrostomy, and breathing irregularities, suggesting that early disease-related multisystem complications may be associated with reduced treatment continuity. These findings complement DAFFODIL and provide early real-world evidence on TROF persistence, restarts, and dosing patterns in this young RTT population.