Real-world Trofinetide Dosing for Rett Syndrome: The LOTUS Study
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical- Pediatric
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Secondary Categories:
- Clinical- Pediatric
Introduction:
Trofinetide is approved by the US Food and Drug Administration for the treatment of Rett syndrome (RTT) in adults and pediatric patients 2 years of age and older. Trofinetide is recommended to be dosed twice a day following weight-banded dosing. Here, we present trofinetide dosing patterns from LOTUS, an observational, prospective, real-world online study of trofinetide in patients with RTT.
Methods:
Caregivers of patients who were prescribed trofinetide under routine clinical care were eligible to participate. Real-world dosing was reported weekly for the first 3 months of the study and then monthly using a caregiver-reported questionnaire.
Results:
In total, 192 respondents were included in this 12-month follow-up. Most participants (>75%) took trofinetide twice daily, while others took it 1 time per day (0—4.7%), 3 times per day (1.9—6.9%) or 4 times per day (0—1.3%). Trofinetide daily dosing (mL/day) increased over follow-up. The median dose (interquartile range [IQR]) reported at Week 1 was 45.0% (20.0—76.0) of target dose in label. By Week 12, the median dose (IQR) was 92.0% (63.3—95.0) of the target dose. Despite different initial trofinetide dosing strategies, the mean trofinetide doses over time converged for the participants who received <75% versus ≥75% of trofinetide target dose as the first recorded dose. The incidence of diarrhea was lower in participants who received <75% versus ≥75% of target dose as first recorded dose at early weeks of treatment, yet most participants did not experience diarrhea regardless of dose. The frequency of diarrhea was similar between participants who received <75% versus ≥75% of target dose as first recorded dose, but the <75% group had fewer clothing changes compared with the ≥75% group over the first 12 weeks of treatment.
Conclusion:
Based on this interim analysis, most patients initiate trofinetide at a lower dose than recommended in the label but increase their dose close to target dose by Week 12 of treatment. Trofinetide dose titration may not influence the overall prevalence of diarrhea but might improve user experience by reducing the incidence in early weeks.
Trofinetide is approved by the US Food and Drug Administration for the treatment of Rett syndrome (RTT) in adults and pediatric patients 2 years of age and older. Trofinetide is recommended to be dosed twice a day following weight-banded dosing. Here, we present trofinetide dosing patterns from LOTUS, an observational, prospective, real-world online study of trofinetide in patients with RTT.
Methods:
Caregivers of patients who were prescribed trofinetide under routine clinical care were eligible to participate. Real-world dosing was reported weekly for the first 3 months of the study and then monthly using a caregiver-reported questionnaire.
Results:
In total, 192 respondents were included in this 12-month follow-up. Most participants (>75%) took trofinetide twice daily, while others took it 1 time per day (0—4.7%), 3 times per day (1.9—6.9%) or 4 times per day (0—1.3%). Trofinetide daily dosing (mL/day) increased over follow-up. The median dose (interquartile range [IQR]) reported at Week 1 was 45.0% (20.0—76.0) of target dose in label. By Week 12, the median dose (IQR) was 92.0% (63.3—95.0) of the target dose. Despite different initial trofinetide dosing strategies, the mean trofinetide doses over time converged for the participants who received <75% versus ≥75% of trofinetide target dose as the first recorded dose. The incidence of diarrhea was lower in participants who received <75% versus ≥75% of target dose as first recorded dose at early weeks of treatment, yet most participants did not experience diarrhea regardless of dose. The frequency of diarrhea was similar between participants who received <75% versus ≥75% of target dose as first recorded dose, but the <75% group had fewer clothing changes compared with the ≥75% group over the first 12 weeks of treatment.
Conclusion:
Based on this interim analysis, most patients initiate trofinetide at a lower dose than recommended in the label but increase their dose close to target dose by Week 12 of treatment. Trofinetide dose titration may not influence the overall prevalence of diarrhea but might improve user experience by reducing the incidence in early weeks.
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