Real-World Benefits and Tolerability of Trofinetide for the Treatment of Adults With Rett Syndrome: the LOTUS Study

Background: Trofinetide is approved for the treatment of Rett syndrome (RTT). The trofinetide clinical trial program limited enrollment to patients with RTT aged 2-20 years. Here, we characterize the real-world benefits and tolerability of trofinetide in the treatment of adults with RTT using the results of the LOTUS study.

Methods: LOTUS is an ongoing, prospective study of patients with RTT prescribed trofinetide in real-world clinical practice. Caregivers of patients who are prescribed trofinetide under routine clinical care are eligible to participate. Assessments include the Behavioral Improvement Questionnaire (BIQ), the Quality-of-Life Inventory-Disability (QI-Disability) Questionnaire, and the Gastrointestinal Health Questionnaire. This analysis is focused on adult patients aged 20 years or older. Data are reported to 12 months since the initiation of trofinetide.

Results: Overall, 77 adult patients with RTT, aged 21-60 years, were included in this analysis. The median dose reported at week 1 was 50.3% of the target weight-banded label dose; dosing ranged from 50.0-66.9% of the target weight-banded label dose between week 5 and month 12. Behavioral improvements reported with the BIQ included nonverbal communication (48–58%), alertness (39–58%), and social interaction/connectedness (32–38%). Modest improvements in patient quality of life were reported. Adult patients were most likely constipated or voided formed/normal stools. The highest incidence of diarrhea was reported at week 2 of treatment (60.0%); most reports were contained inside the patient’s diaper.

Conclusion: The real-world benefits and tolerability of trofinetide in adults with RTT in LOTUS followed similar trends to the overall LOTUS population.