Real-world benefits and tolerability of trofinetide for the treatment of Rett syndrome: The LOTUS study

Aim: To describe the real-world effects of trofinetide in individuals with Rett syndrome (RTT) using the 18-month follow-up analysis of the LOTUS study. Method: Caregivers of any patients who were prescribed trofinetide under routine clinical care were eligible to participate. Assessments included the Behavioral Improvement Questionnaire (BIQ), the Quality of Life Inventory-Disability (QI-Disability) questionnaire, the Gastrointestinal Health Questionnaire, and safety monitoring. Data are reported to 12 months since the initiation of trofinetide. Results: Overall, 227 caregivers participated in this follow-up. The median trofinetide dose at week 1 was 36.0% of the target dose and increased to over 80% by week 10 onwards; 55.2% of patients took the full trofinetide recommended daily dose. Caregivers (71%–90%) reported behavioral improvements across months 1 to 12 with the BIQ, including non-verbal communication (48%–71%), alertness (44%–70%), and social interaction and connectedness (33%–58%). The median QI-Disability total score change from baseline ranged from 4.7 to 4.6 in months 1 to 12. The incidence of diarrhea varied from weeks 1 to 12 (23%–50%) and months 4 to 12 (26%–38%); most reports of diarrhea were contained inside the patient's diaper. Safety reports were consistent with previous trofinetide clinical trials. Interpretation: Results from the LOTUS study show improvements in the symptoms of RTT, with early insights into managing gastrointestinal symptoms in the context of real-world patient care.