Rett syndrome and real-world treatment patterns of trofinetide in the United States

BACKGROUND: Trofinetide (TROF) remains the first and only FDA-approved pharmacologic treatment for Rett syndrome (RTT). There is limited real-world evidence on TROF use, restarts, dosing patterns and predictors of non-persistence. This study evaluated long-term treatment patterns and baseline predictors of non-persistence among RTT individuals initiating TROF. METHODS: TROF prescription (RX) between 1 April 2023 and 31 March 2024 with ≥6 months of pre- and post-index continuous enrollment were classified as persistent (gap ≤90 days) and non-persistent. Median (IQR) time on treatment was analyzed, and Kaplan-Meier assessed time to non-persistence. Restarts among non-persistent were examined. Dosing patterns such as mean dose in milligrams (mg) and percentage target daily dose (%TDD) at each RX were evaluated. Predictors of non-persistence were assessed using logistic regression. RESULTS: Among 1,175 TROF initiators, 54.9% were persistent and 45.1% were non-persistent; 7.6% of non-persistent individuals restarted. Mean ± SD age was 14.7 ± 10.8 vs. 16.5 ± 11.6 years and median ± IQR time on TROF was 14.3 ± 4.6 vs. 3.0 ± 3.8 months, respectively. Over 75% remained on treatment beyond 3 months, and more than half continued through study follow-up. Mean twice daily (BID) TROF dose was lower among persistent (7422.0 mg) vs. non-persistent (7850.8 mg) at RX1 and increased to 7953.7 mg vs 8423.4 mg, respectively at RX2. Thereafter, the persistent individuals maintained stable dosing, while the non-persistent showed greater fluctuation over time. Similar patterns were observed for %TDD. Older age and history of infectious disorders were significantly associated with non-persistence. CONCLUSIONS: In this real-world analysis, more than half of RTT individuals remained persistent on TROF for ≥14 months. Stable dosing patterns were observed among persistent individuals, while greater dose variability was observed among non-persistent individuals. Thus, these findings may provide guidance to clinicians about long-term TROF use in real-world practice.