Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort.
Infantile spasms (IS) represent a severe epileptic encephalopathy presenting in the first 2 years of life. Recommended first-line therapies (hormonal therapy or vigabatrin) often fail. We evaluated response to second treatment for IS in children in whom the initial therapy failed to produce both clinical remission and electrographic resolution of hypsarhythmia and whether time to treatment was related to outcome.



The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of IS. Children were considered nonresponders to first treatment if there was no clinical remission or persistence of hypsarhythmia. Treatment was evaluated as hormonal therapy (adrenocorticotropic hormone [ACTH] or oral corticosteroids), vigabatrin, or "other." Standard treatments (hormonal and vigabatrin) were compared to all other nonstandard treatments. We compared response rates using chi-square tests and multivariable logistic regression models.



One hundred eighteen infants were included from 19 centers. Overall response rate to a second treatment was 37% (n = 44). Children who received standard medications with differing mechanisms for first and second treatment had higher response rates than other sequences (27/49 [55%] vs. 17/69 [25%], p < 0.001). Children receiving first treatment within 4 weeks of IS onset had a higher response rate to second treatment than those initially treated later (36/82 [44%] vs. 8/34 [24%], p = 0.040).



Greater than one third of children with IS will respond to a second medication. Choosing a standard medication (ACTH, oral corticosteroids, or vigabatrin) that has a different mechanism of action appears to be more effective. Rapid initial treatment increases the likelihood of response to the second treatment.
Department of Pediatrics and Neurology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, U.S.A.
Kelly G
KG
Knupp
Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, U.S.A.
Erin
E
Leister
Departments of Pediatrics and Neurology, School of Medicine, Oregon Health & Sciences University, Portland, Oregon, U.S.A.
Jason
J
Coryell
Departments of Neurology and Pediatrics, Mayo Clinic, Rochester, Minnesota, U.S.A.
Katherine C
KC
Nickels
Division of Neurology, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.
Nicole
N
Ryan
Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, U.S.A.
Elizabeth
E
Juarez-Colunga
Center For Neuroscience, Children's National Health System, Washington, District of Columbia, U.S.A.
William D
WD
Gaillard
Division of Pediatric Neurology, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, U.S.A.
John R
JR
Mytinger
Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, U.S.A.|Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, U.S.A.
Anne T
AT
Berg
Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, U.S.A.|Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, U.S.A.
John
0000-0002-0798-0131
J
Millichap
Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, U.S.A.|Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, U.S.A.
Douglas R
DR
Nordli
Department of Pediatrics & Communicable Diseases (Division of Pediatric Neurology), University of Michigan, Ann Arbor, Michigan, U.S.A.
Sucheta
S
Joshi
Department of Pediatrics & Communicable Diseases (Division of Pediatric Neurology), University of Michigan, Ann Arbor, Michigan, U.S.A.
Renée A
RA
Shellhaas
Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, U.S.A.
Tobias
T
Loddenkemper
Division of Neurology, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.
Dennis
D
Dlugos
Departments of Neurology and Pediatrics, Mayo Clinic, Rochester, Minnesota, U.S.A.
Elaine
E
Wirrell
Departments of Pediatrics and Neurology, University of California San Francisco, San Francisco, California, U.S.A.
Joseph
J
Sullivan
Departments of Neurology and Pediatrics, Johns Hopkins Hospital, Baltimore, Maryland, U.S.A.
Adam L
AL
Hartman
Departments of Neurology and Pediatrics, Johns Hopkins Hospital, Baltimore, Maryland, U.S.A.
Eric H
EH
Kossoff
Departments of Pediatrics and Healthcare Policy & Research, Weill Cornell Medical Center, New York, New York, U.S.A.
Zachary M
ZM
Grinspan
Department of Neurology, University of Washington, Seattle, Washington, U.S.A.
Lorie
L
Hamikawa
D000324:Adrenocorticotropic Hormone / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D013036:Spasms, Infantile / Q000188:drug therapy*; D017211:Treatment Failure; D020888:Vigabatrin / Q000627:therapeutic use*
D000927:Anticonvulsants; D000324:Adrenocorticotropic Hormone; D020888:Vigabatrin
Adrenocorticotropic hormone; Infantile spasms; Second-line treatment; Vigabatrin