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Response to sequential treatment with prednisolone and vigabatrin in infantile spasms
Winston Dzau1, Sally Cheng2, Penny Snell3
1Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
Insights
Prednisolone is more effective than vigabatrin for infantile spasms (IS) initial treatment. The UKISS sequence shows high response rates, with subsequent treatments offering similar benefits for non-responders.
Area of Science:
- Pediatric Neurology
- Neonatology
- Clinical Pharmacology
Background:
- Infantile spasms (IS) is a severe epilepsy syndrome in infants.
- Early treatment is crucial for optimal neurodevelopmental outcomes.
- Treatment guidelines recommend specific sequences, but real-world effectiveness varies.
Purpose of the Study:
- To evaluate the effectiveness of first-line treatments for infantile spasms (IS).
- To assess the incremental benefit of prednisolone and vigabatrin in the UKISS treatment sequence.
- To identify potential treatment gaps in IS management.
Main Methods:
- Retrospective analysis of 151 infants with IS.
- Comparison of prednisolone, vigabatrin, and nonstandard treatments as first-line therapy.
- Evaluation of response to sequential treatments within the UKISS protocol.
Main Results:
- Prednisolone achieved significantly higher spasm cessation rates (63%) compared to vigabatrin (28%) or nonstandard treatments (5.9%) as first-line therapy.
- In the UKISS sequence, 63% responded to initial prednisolone (40 mg/day).
- Subsequent treatments showed similar response rates: 41% for higher-dose prednisolone (60 mg/day) and 45% for vigabatrin in non-responders.
Conclusions:
- Initial prednisolone treatment demonstrates superior efficacy for infantile spasms compared to vigabatrin or nonstandard therapies.
- A significant proportion of infants do not receive prednisolone as first-line treatment, indicating a treatment gap.
- The UKISS treatment sequence is highly effective, with subsequent prednisolone or vigabatrin providing comparable benefits for non-responders.
Aim:
To report response to first treatment in infants with infantile spasms (IS), including incremental benefit of prednisolone 60 mg/day and vigabatrin following prednisolone 40 mg/day failure in infants commenced on the United Kingdom Infantile Spasms Study (UKISS) treatment sequence.
Methods:
In this retrospective analysis, we compared effectiveness of prednisolone, vigabatrin and nonstandard treatments as first treatment for IS. In infants who commenced the UKISS treatment sequence, we evaluated response to each step. Primary outcome was spasm cessation after 42 days. Secondary outcomes were severe side effects and spasm relapse after 42 days.
Results:
Treatment response data were available for 151 infants. First treatment was prednisolone in 99 infants, vigabatrin in 18 and nonstandard treatment in 34. The rate of spasm cessation with first treatment was significantly higher with prednisolone (62/99, 63%) than vigabatrin (5/18, 28%, P = 0.01) or nonstandard treatment (2/34, 5.9%, P < 0.01). Of 112 infants who commenced the UKISS treatment sequence, 71/112 (63%) responded to prednisolone 40 mg/day. Among non-responders, 12/29 (41%) subsequently responded to prednisolone 60 mg/day, and 10/22 (45%) to vigabatrin. Severe side effects and spasm relapse were not significantly different between each treatment.
Conclusion:
We confirm higher rates of spasm cessation with initial treatment with prednisolone than vigabatrin and nonstandard therapy. Non-use of prednisolone as first treatment in over one third of infants highlights a concerning treatment gap. The UKISS treatment sequence has high overall treatment response (total 93/112; 83%), with similar benefit of subsequent prednisolone 60 mg/day and vigabatrin in prednisolone 40 mg/day non-responders.
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