Trofinetide treatment of Rett syndrome during routine health care: a plain language summary of the LOTUS study

Plain Language SummaryWhat is this summary about?This is a plain language summary of an article published in Developmental Medicine and Child Neurology in 2025. The article describes the results of the LOTUS study. LOTUS involved caregivers of people living with Rett syndrome, a rare genetic condition that affects the way the brain develops. Rett syndrome mainly affects girls, causing them to lose skills like speaking, walking and using their hands in early childhood. Even more rarely, Rett syndrome can affect boys.What happened in the LOTUS study?In this study, researchers looked at how well trofinetide worked in people with Rett syndrome in the United States who were taking trofinetide as part of their normal health care. Caregivers filled in online questionnaires about their loved one’s symptoms and quality of life at regular intervals for 12 months after they started taking trofinetide.What were the results and what do they mean?Overall, 227 caregivers of adults and children with Rett syndrome took part in the study. At the start of the study participants took 36% of the recommended daily dose of trofinetide. After 6 months, on average the dose increased to 92% of the recommended daily dose. In total, 90% of caregivers reported behavioral improvements after 12 months of trofinetide treatment, with improvements in non-verbal communication, alertness, and social interaction/connectedness being reported most often. People with Rett syndrome also showed some improvement in their quality of life after 12 months of taking trofinetide. Most caregivers (79%) reported diarrhea at some point during the first 3 months of trofinetide treatment. However, most diarrhea episodes were contained by the person’s diaper and normal stools were common during the study. About one-quarter (26.4%) of people with Rett syndrome had a side effect while taking trofinetide. The most common side effects were diarrhea, vomiting and constipation. The results of the LOTUS study show that trofinetide improved symptoms in people with Rett syndrome who were taking the treatment as part of their routine health care.How to say (download PDF and double click sound icon to play sound)…DAYBUE: DAY-byooPlacebo: pluh-SEE-boStereotypies: STEH-ree-oh-TIE-peesTrofinetide: troh-FIN-uh-tideThis is an abstract of the Plain Language Summary of Publication article.