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Comparative Effectiveness of Initial Treatment for Infantile Spasms in a Contemporary US Cohort
Zachary M Grinspan1, Kelly G Knupp2, Anup D Patel2
1From Weill Cornell Medicine (Z.M.G.), New York, NY; University of Colorado Anschutz Medical Campus (K.G.K.), Aurora; Nationwide Children's Hospital (A.D.P., J.R.M.), Ohio State University, Columbus; Montefiore Medicine (E.G.Y.), Bronx, NY; Stanford University (C.J.W.), Palo Alto, CA; Mayo Clinic (E.W.), Rochester, MN; Drexel University College of Medicine (I.V.), Philadelphia, PA; University of California San Francisco (N.S.S.); University of Chicago Medicine (D.R.N.), IL; Children's Hospital of Los Angeles (W.M.), CA; Cook Children's Hospital (C.G.K.), Fort Worth, TX; Boston Children's Hospital (T.L., C.H., I.S.F.), MA; University of California Los Angeles (S.A.H.); Children's National Hospital (W.D.G.), Washington, DC; Oregon Health Services University (J.C.), Portland; Massachusetts General Hospital (C.J.C.), Boston; Lurie Children's Hospital (A.T.B.), Chicago, IL; and University of Michigan (R.A.S.), Ann Arbor. zag9005@med.cornell.edu.
Insights
Adrenocorticotropic hormone (ACTH) and oral steroids are more effective initial treatments for infantile spasms than nonstandard therapies. Vigabatrin showed intermediate effectiveness, particularly in children with tuberous sclerosis complex (TSC).
Area of Science:
- Pediatric Neurology
- Clinical Pharmacology
- Evidence-Based Medicine
Background:
- Infantile spasms (IS) are a severe epilepsy syndrome in infants.
- Optimal initial treatment strategies for IS remain a critical clinical question.
- Early effective treatment is crucial to prevent developmental impairment.
Purpose of the Study:
- To compare the effectiveness of different initial treatments for new-onset infantile spasms.
- To provide evidence to guide clinical decision-making for IS management.
Main Methods:
- Prospective cohort study of children with new-onset IS (age 2-24 months) across 23 US centers (2012-2018).
- Freedom from treatment failure at 60 days defined as no second treatment and no clinical spasms after 30 days.
- Propensity score weighting and generalized estimating equations used to manage treatment selection bias.
Main Results:
- Freedom from treatment failure rates: ACTH 46%, oral steroids 44%, vigabatrin 37%, nonstandard therapy 8%.
- ACTH and oral steroids demonstrated superior effectiveness compared to nonstandard therapies.
- Vigabatrin's effectiveness was intermediate; it showed higher response rates in children with TSC (62% vs. 29%).
Conclusions:
- Adrenocorticotropic hormone (ACTH) and oral steroids are superior initial treatments for infantile spasms compared to nonstandard therapies.
- Vigabatrin's effectiveness is between that of ACTH/oral steroids and nonstandard therapies, though the study was underpowered for definitive conclusions.
- Vigabatrin is most effective in patients with tuberous sclerosis complex (TSC).
Objective:
To compare the effectiveness of initial treatment for infantile spasms.
Methods:
The National Infantile Spasms Consortium prospectively followed up children with new-onset infantile spasms that began at age 2 to 24 months at 23 US centers (2012-2018). Freedom from treatment failure at 60 days required no second treatment for infantile spasms and no clinical spasms after 30 days of treatment initiation. We managed treatment selection bias with propensity score weighting and within-center correlation with generalized estimating equations.
Results:
Freedom from treatment failure rates were as follows: adrenocorticotropic hormone (ACTH) 88 of 190 (46%), oral steroids 42 of 95 (44%), vigabatrin 32 of 87 (37%), and nonstandard therapy 4 of 51 (8%). Changing from oral steroids to ACTH was not estimated to affect response (observed 44% estimated to change to 44% [95% confidence interval 34%-54%]). Changing from nonstandard therapy to ACTH would improve response from 8% to 39% (17%-67%), and changing to oral steroids would improve response from 8% to 38% (15%-68%). There were large but not statistically significant estimated effects of changing from vigabatrin to ACTH (29% to 42% [15%-75%]), from vigabatrin to oral steroids (29% to 42% [28%-57%]), and from nonstandard therapy to vigabatrin (8% to 20% [6%-50%]). Among children treated with vigabatrin, those with tuberous sclerosis complex (TSC) responded more often than others (62% vs 29%; p < 0.05).
Discussion:
Compared to nonstandard therapy, ACTH and oral steroids are superior for initial treatment of infantile spasms. The estimated effectiveness of vigabatrin is between that of ACTH/oral steroids and nonstandard therapy, although the sample was underpowered for statistical confidence. When used, vigabatrin worked best for TSC.
Classification Of Evidence:
This study provides Class III evidence that for children with new-onset infantile spasms, ACTH or oral steroids were superior to nonstandard therapies.
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