Trofinetide Use and Treatment Patterns Among Children Aged 2-4 Years with Rett Syndrome in the United States: A Retrospective Specialty Pharmacy Linked Claims Database Analysis.

内容摘要

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. Why was the study done? Rett syndrome is a rare genetic disorder that impacts brain development, primarily in young girls. In March 2023, the drug trofinetide became the first approved treatment for this condition in the United States. While clinical trials showed the drug is safe and effective for young children aged 2 to 4, doctors and families need real-world evidence to see how well children stick with the treatment in everyday life outside of strict trial settings. What did the researchers do and find? We analyzed health insurance and pharmacy data for 159 children aged 2 to 4 with Rett syndrome who started trofinetide between April 2023 and March 2024. We looked at how long they stayed on the medication, their daily dosages, and whether those who stopped eventually restarted. Our study revealed that: Two-thirds of the children (65.4%) successfully stayed on their trofinetide treatment continuously for over a year.Children who stopped taking the medication usually did so around the 4-month mark. However, about 14.5% of those children eventually restarted the drug after a break.Children who stopped the medication had higher rates of other health issues before starting, such as stomach problems and seizures, compared to those who stayed on it. What do these results mean? Real-world data shows most young children with Rett syndrome stay on trofinetide long-term. Since those with more pre-existing health issues often stop treatment, doctors can use this information to closely support high-risk patients.