Zachary M Grinspan1, Kelly G Knupp2, Anup D Patel3, Elissa G Yozawitz4, Courtney J Wusthoff5, Elaine Wirrell6, Ignacio Valencia7, Nilika S Singhal8, Douglas R Nordli9, John R Mytinger3, Wendy Mitchell10, Cynthia G Keator11, Tobias Loddenkemper12, Shaun A Hussain13, Chellamani Harini12, William D Gaillard14, Ivan S Fernandez12, Jason Coryell15, Catherine J Chu16, Anne T Berg17, Renee A Shellhaas18. 1. Weill Cornell Medicine, New York, NY zag9005@med.cornell.edu. 2. University of Colorado Anschutz Medical Campus, Aurora, CO. 3. Nationwide Children's Hospital, Ohio State University, Columbus, OH. 4. Montefiore Medicine, Bronx, NY. 5. Stanford University, Palo Alto, CA. 6. Mayo Clinic, Rochester, MN. 7. Drexel University College of Medicine, Philadelphia, PA. 8. University of California San Francisco, San Francisco, CA. 9. University of Chicago Medicine, Chicago, IL. 10. Children's Hospital of Los Angeles, Los Angeles, CA. 11. Cook Children's Hospital, Fort Worth, TX. 12. Boston Children's Hospital, Boston, MA. 13. University of California Los Angeles, Los Angeles, CA. 14. Children's National Hospital, Washington, DC. 15. Oregon Health Services University, Portland, OR. 16. Massachusetts General Hospital, Boston, MA. 17. Lurie Children's Hospital, Chicago, IL. 18. University of Michigan, Ann Arbor, MI.
Abstract
OBJECTIVE: Compare the effectiveness of initial treatment for infantile spasms. METHODS: The National Infantile Spasms Consortium prospectively followed children with new onset infantile spasms that began at age 2-24 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: ACTH 88/190 (46%), oral steroids 42/95 (44%), vigabatrin 32/87 (37%), and non-standard therapy 4/51 (8%). Changing from oral steroids to ACTH was not estimated to affect response (observed 44% estimated to change to 44% [95% CI 34-54]). Changing from non-standard therapy to ACTH would improve response from 8% to 39 [17-67]%, and to oral steroids 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]%), vigabatrin to oral steroids (29% to 42 [28-57]%), and non-standard 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) CONCLUSION: Compared to non-standard therapy, ACTH and oral steroids are superior for initial treatment of infantile spasms. The estimated effectiveness of vigabatrin is between ACTH / oral steroids and non-standard therapy, though 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 non-standard therapies.
OBJECTIVE: Compare the effectiveness of initial treatment for infantile spasms. METHODS: The National Infantile Spasms Consortium prospectively followed children with new onset infantile spasms that began at age 2-24 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: ACTH 88/190 (46%), oral steroids 42/95 (44%), vigabatrin 32/87 (37%), and non-standard therapy 4/51 (8%). Changing from oral steroids to ACTH was not estimated to affect response (observed 44% estimated to change to 44% [95% CI 34-54]). Changing from non-standard therapy to ACTH would improve response from 8% to 39 [17-67]%, and to oral steroids 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]%), vigabatrin to oral steroids (29% to 42 [28-57]%), and non-standard 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) CONCLUSION: Compared to non-standard therapy, ACTH and oral steroids are superior for initial treatment of infantile spasms. The estimated effectiveness of vigabatrin is between ACTH / oral steroids and non-standard therapy, though 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 non-standard therapies.
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