Data from a survey presented at the American Epilepsy Society (AES) 2024 Annual Meeting in Los Angeles, California, suggests that titrating trofinetide (Daybue; Acadia Pharmaceuticals) improves tolerability among treatment-naive patients with Rett syndrome. The survey, which included responses from 22 individuals prescribing trofinetide, indicated that 86% of them found titration to be beneficial in enhancing tolerability.
The survey, sent in May 2024 to 33 prescribers at 18 US Rett syndrome centers of excellence (COEs) designated by the International Rett Syndrome Foundation, featured 22 prescribers from 16 COEs. These prescribers accounted for 38.1% of trofinetide prescriptions in the United States since its approval.
Key Findings on Tolerability
The survey revealed that 86% (n = 19) of participants reported that titrating trofinetide improved tolerability in treatment-naïve patients. Specific improvements observed included decreased diarrhea severity (77%, n = 17), decreased trofinetide discontinuations (73%, n = 16), improved caregiver quality of life (64%, n = 14), and improved patient quality of life (59%, n = 13).
Erin Prange, MSN, CRNP, a nurse practitioner in the Division of Neurology at Children's Hospital of Philadelphia, led the investigation. The survey explored real-world dosing strategies and their impact on tolerability, as diarrhea was identified as the most common adverse event and the leading cause of treatment discontinuation in clinical trials of trofinetide.
Challenges and Discontinuation Rates
Despite the positive impact of titration on tolerability, participants noted that approximately 20% of patients could still discontinue trofinetide treatment due to tolerability issues. Discontinuation due to lack of efficacy was estimated to be between 5% and 8%.
Some prescribers provided additional context. One prescriber noted, "Some patients do not like the taste; another vomits even with 5 mL dose." Another stated, "I think there are patients that it doesn’t matter for, patients it is critical for, and patients that don’t tolerate no matter what we do."
Broader Implications for Prescribing
Alan Percy, MD, Professor of Pediatrics, Neurology, Neurobiology, Genetics, and Psychology at the University of Alabama, Birmingham, previously noted that general pediatricians can play a significant role in prescribing trofinetide. He estimated that up to 50% of children receiving the medication have had it prescribed by their private physician. Percy emphasized that general physicians should feel confident in prescribing trofinetide, with COEs offering guidance and support to bridge any knowledge gaps.
Conclusion
The investigators concluded that prescribers believe trofinetide titration helps with overall tolerability, specifically to decrease diarrhea severity and treatment discontinuations while improving patient and caregiver quality of life. This real-world evidence supports the use of titration strategies to optimize the benefits of trofinetide in treating Rett syndrome.
