To characterize the real-world benefits and tolerability of trofinetide in the treatment of Rett syndrome (RTT) using the 12-month follow-up of the ongoing LOTUS study.

Trofinetide is approved for the treatment of RTT in patients aged ≥2 years in the United States and patients aged ≥2 years weighing at least 9 kg in Canada. Results from quantitative measures from trofinetide clinical trials have generated interest among clinicians and caregivers in practical, real-world outcomes associated with trofinetide treatment.

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. Due to ongoing enrollment, data are reported to 9 months since the initiation of trofinetide.

In total, 192 patients were included in this follow-up. The median dose reported at week 1 was 45.0% of the target weight-banded label dose; by week 9 onwards, the median dose was at least 80.0% of the target weight-banded label dose. Behavioral improvements reported with the BIQ were nonverbal communication (49–62%), alertness (43–62%), and social interaction/connectedness (32–52%). The QI-Disability Questionnaire median total scores indicated overall improvement in patient quality of life (QoL) with trofinetide. Caregivers reported that patients were most likely to void normal stools over the follow-up; most reports of diarrhea were contained inside the patient’s diaper. Response patterns to trofinetide were similar among pediatric and adult patients, suggesting that trofinetide responses do not clearly differ across age groups.

Caregivers of patients with RTT in LOTUS reported behavioral improvements of RTT symptoms and improvement in patients’ QoL.