Authors :
David Lieberman, MD – Boston Children's Hospital
Grace Correa, MSN, RN, CPNP – Boston Children's Hospital
Arthur Beisang, MD – Gillette Children's Specialty Healthcare
Robin Ryther, MD, PhD – Washington University School of Medicine
Christopher Beatty, MD, MAS – Nationwide Children's Hospital, The Ohio State University
Emily De Los Reyes, MD – Nationwide Children's Hospital, The Ohio State University College of Medicine
Bernhard Suter, MD – Baylor College of Medicine
Alan Percy, MD – University of Alabama at Birmingham
Amitha Ananth, MD – University of Alabama at Birmingham
Caroline Buchanan, MD – Greenwood Genetic Center
Louise Cosand, PhD – Acadia Pharmaceuticals Inc.
Presenting Author: Alyssa Peckham, PharmD, BCPP – Acadia Pharmaceuticals Inc.
Rationale:
Trofinetide was approved by the US Food and Drug Administration in March 2023 for treating Rett syndrome in patients aged ≥2 years, with twice daily weight-banded dosing. Here, we present real-world examples of alternative dosing strategies.
Methods:
In May 2024, a prescriber experience survey was sent to prescribers at US Rett syndrome centers of excellence (COEs) to collect real-world trofinetide dosing strategies, dosing considerations, and achievable dose.Results:
Overall, 67% (22/33) prescribers from 89% (16/18) COEs participated, accounting for 4.6% of trofinetide prescribers and 38.1% of trofinetide prescriptions nationwide. Most survey respondents (95%, n=21) indicated that they titrate trofinetide in treatment-naïve patients. Most titration strategies included initiating at a lower percentage (50%, n=11) or milliliters (27%, n=6) than target dose. Others individualized starting dose based on baseline conditions, such as diarrhea, constipation, or target dose (14%, n=3). Other dosing strategies included weight-based dosing and three- or four-times daily dosing to address tolerability. In total, 70-75% of patients achieve their weight-banded dose after titration. Of the 25-30% who do not, they achieve an average of 75% of their weight-banded dose. Following titration, survey respondents encourage families to remain on trofinetide for an average of 4-5 months to adequately evaluate efficacy.Conclusions:
Trofinetide dose titration is common at COEs, with several titration strategies available. Titration allows for most patients to reach their weight-banded dose, though some are maintained at a lower dose. Prescribers believe that patients should try trofinetide for 4-5 months at their highest tolerable dose to adequately assess efficacy.
Funding:
Acadia Pharmaceuticals Inc.