Recommendations for the management of diarrhea with trofinetide use in Rett syndrome

ABSTRACT Background Trofinetide is a recently approved treatment for Rett syndrome (RTT), a rare neurodevelopmental disorder with no previously approved therapy. The phase 3 LAVENDER trial showed improvements in efficacy measures compared with placebo, but diarrhea rates were high in trofinetide-treated participants. To manage possible diarrhea, recommendations that can be used by health care providers are needed. Research design and methods Additional analyses were conducted on LAVENDER data to elucidate predictors of trofinetide-associated diarrhea. A panel of advisors was convened to refine a set of practical recommendations for the prevention and management of diarrhea in individuals with RTT treated with trofinetide. Results No examined demographic or treatment factors appeared to influence trofinetide-associated diarrhea. Advisors recommend establishing baseline bowel activity and providing caregivers with diarrhea management information. On initiation of trofinetide, constipation medications should be stopped or reduced, concomitant liquid medications with sugar alcohols should be substituted if possible, and fiber should be initiated. Bowel movements should be tracked and loperamide started following the onset of diarrhea. Dietary and hydration measures are also recommended. Conclusions Trofinetide treatment confers improvements in RTT-related symptoms. With these recommendations, diarrhea associated with trofinetide use can be managed, enhancing the lives of individuals with RTT and caregivers.