Efficacy and safety of trofinetide in patients with Rett syndrome: a systematic literature review

Abstract

Introduction Rett syndrome (RTT) is a rare neurodevelopmental disorder with limited treatment options. Trofinetide has emerged as a potential therapeutic agent due to its neuroprotective and anti-inflammatory properties. This systematic review evaluates the efficacy and safety of trofinetide in patients with Rett syndrome. Methods We identified 44 articles from two databases (PubMed and Scopus). After removing duplicates, we applied the inclusion criteria, which were restricted to systematic reviews and meta-analyses of randomized controlled trials (RCTs) published within the last 5 years, available in English, and reporting efficacy outcomes measured with validated tools such as the Rett Syndrome Behavior Questionnaire (RSBQ) and the Clinical Global Impression-Improvement (CGI-I). Non-randomized trials and studies with insufficient data were excluded. Results This review included three studies with 916 patients on trofinetide for Rett syndrome. Trofinetide showed significant improvements in RSBQ (MD: -3.40 to -3.53) and CGI-I scores (MD: -0.34 to -0.35). Common side effects were diarrhea and vomiting, but no severe adverse events were reported. Conclusions This systematic review supports the efficacy of trofinetide in improving behavioral and functional outcomes in Rett syndrome. The treatment demonstrated significant reductions in symptom severity, particularly in communication and motor skills, as measured by the Rett Syndrome Behavior Questionnaire (RSBQ) and Clinical Global Impression-Improvement (CGI-I). While trofinetide was generally well-tolerated, common side effects like diarrhea and vomiting were reported. Further research with longer follow-up periods is needed to confirm the long-term efficacy and safety of trofinetide in RTT patients.