Efficacy and Safety of Trofinetide in Patients with Rett Syndrome: A Systematic Review and Meta-analysis
Mohamed Abo Zeid1, Amr Elrosasy2, Elarbi Goufa3, Alina Ghazou4, Nourhan Hassan 5, Rashad Gamal Mohamed6, Ahmed Negida7
1Faculty of Medicine Tanta University, 2Faculty Of Medicine, Cairo University, Cairo, Egypt, 35. Faculty of Medicine, University of Oran 1 - Ahmed Ben Bella, Algeria, 44. Faculty of Medicine, Jordan University of Science and Technology., 56. Faculty of Medicine, Zagazig University, Egypt., 63. Mansoura Manchester Program for Medical Education, Faculty of Medicine, Mansoura University, Egypt., 7Virginia Commonwealth University
Objective:

The purpose of this meta-analysis is to evaluate the efficacy and safety of trofinetide in treating Rett syndrome patients.

Background:
Rett syndrome (RTT) is an uncommon inherited neurological and developmental disorder that has an impact on brain development, mostly in females. It results from a gene mutation in the long chain (q) of the X chromosome. Trofinetide is a recently developed drug that has a neuroprotective effect on neurons and was found to improve respiratory and cardiac functions as well in patients with Rett syndrome. 
Design/Methods:

We followed the PRISMA guidelines to conduct this meta-analysis. We searched databases to identify randomized controlled trials (RCTs) related to the use of trofinetide in patients with Rett syndrome until 13 August 2023. The methodological quality of randomized controlled trials (RCTs) was evaluated using the Cochrane risk-of-bias tool for randomized trials (RoB-2). Our primary outcomes are the Clinical Global Impression-Improvement (CGI) and the Rett syndrome Behavior Questionnaire (RSBQ). Whereas adverse events (AEs) are secondary outcomes.

Results:

Three RCTs with a total of 325 patients were included with a follow-up duration ranging from one month to three months. One hundred and eighty-seven (187) patients received the intervention drug (Trofinetide) and 138 received the placebo. Trofinetide was found to reduce CGI and RSBQ significantly more than placebo (MD = -0.35, 95% CI [-0.52 to -0.18], P 0.0001), (MD = -3.40, 95% CI [-3.69 to -3.12], P 0.00001) respectively. Most adverse events did not show any statistical difference between Trofinetide and the placebo.

Conclusions:

Trofinetide is a potential effective therapy for Rett syndrome, with improvements seen on both CGI and RSBQ assessments.

10.1212/WNL.0000000000205608