Adrenocorticotropic hormone, oral steroids superior for new-onset infantile spasms

Adrenocorticotropic hormone and oral steroids demonstrated superiority compared with non-standard therapy for the initial treatment of infantile spams in a prospective, multicenter observational cohort study published in Neurology.

“There are three recommended first treatments for infantile spasms: oral corticosteroids (typically prednisolone in the United States), adrenocorticotropic hormone (ACTH) and vigabatrin. Each medication has a different proposed mechanism of action,” the researchers wrote. “Our published analysis of a rigorous prospective multicentered observational study of infants with infantile spasms (the National Infantile Spasms Consortium; NISC) suggested the superiority of ACTH over other treatments. However, our findings were based on a preliminary analysis of an active registry and did not fully account for treatment selection bias and center-to-center variations.”

The researchers also pointed to other concerns about the analysis, including poor inter-rater reliability with a primary outcome as well as the possibility that responses rates “may not be appreciably different between ACTH (or tetracosactide) and oral steroids,” which provided additional support for a reanalysis.

Zachary M. Grinspan, MD, MS, interim chief of child neurology and director of the pediatric epilepsy program at Weill Cornell Medicine and NewYork-Presbyterian Komansky Children's Hospital at Weill Cornell Medical Center and assistant professor of pediatrics and population health sciences, and colleagues aimed to compare the efficacy of initial treatment for infantile spasms. The researchers used data from the NISC, which prospectively followed children at 23 U.S. centers with new-onset infantile spasms that started between ages 2 months and 24 months between 2012 and 2018.

Outcomes focused on seizures, where infants were considered free from treatment failure at 60 days if no second prescription within 60 days was required and freedom from infantile spams started within 30 days of treatment initiation. The researchers reported how frequently children required a second treatment and how often they were free from infantile spasms regardless of the use of additional treatments.

The analysis cohort included 423 infants. Most infants (n = 190) received ACTH. The rest of the infants in the analysis received oral steroids (prednisolone, n = 73; prednisone, n = 22), vigabatrin (n = 87) and nonstandard therapies (n = 51). Nonstandard treatments included topiramate (n = 29), levetiracetam (n = 8), clobazam (n = 5), zonisamide (n =3), dietary therapies (n = 3), rufinamide (n = 2) and oxcarbazepine (n = 1).

Study results demonstrated that rates of freedom from treatment failure were 46% with ACTH (88/190), 44% with oral steroids (42/95), 37% with vigabatrin (32/87) and 8% with non-standard therapy (4/51). The researchers found that switching from oral steroids to ACTH was not estimated to impact response (observed 44% estimated to change to 44%; 95% CI, 34-54). Shifting from non-standard therapy to ACTH would increase response from 8% to 39% (95% CI, 17-67) and from 8% to 38% (95% CI, 15-68) for a switch to oral steroids.

Grinspan and colleagues observed large, but not statistically significant, estimated effects of switching from vigabatrin to ACTCH (29% to 42%; 95% CI, 15-75), vigabatrin to oral steroids (29% to 42%; 95% CI, 28-57) and non-standard therapy to vigabatrin (8% to 20%; 95% CI, 6-50). Among children who received vigabatrin, those with tuberous sclerosis complex responded more frequently than other children (62% vs. 29%; P < .05).

“We provide real-world head-to-head comparisons of different treatments for infantile spams. Among children with infantile spasms, treatment with anything other than the three recommended therapies resulted in a dismal response: Only 4 of 51 were free from treatment failure,” Grinspan and colleagues wrote. “By our estimates, ACTH would have led to freedom from failure in 20 of the 51 and oral steroids would have led to freedom from failure in 19 of the 51. The E-values were high (9.2 and 9), suggesting that unmeasured confounding is unlikely to explain away these findings.”

The results also provided additional support for the American Academy of Neurology quality measure that recommends ACTH, prednisolone or vigabatrin as first-line therapy for infantile spasms, according to the researchers.

“Recent trial data suggest combination therapy (vigabatrin plus hormonal therapy) may improve short-term response rate compared to hormonal therapy alone, though with uncertain effect on developmental outcomes. Additional studies are needed to clarify the role of combination therapy,” Grinspan and colleagues wrote. “The observation that ACTH may resolve hypsarrhythmia more quickly than oral steroids also merits additional study.”