Cosyntropin More Effective for Short-Term Outcomes Than Vigabatrin in Infantile Spasms Syndrome


Although findings suggest better efficacy of consyntropin when compared with vigabatrin, the randomized trial was underpowered due to incomplete enrollment.

Kelly G. Knupp, MD, MSCS, FAES, associate professor of pediatrics and neurology, and codirector, neurology research, University of Colorado, Anschutz Campus, in Aurora, Colorado

Kelly G. Knupp, MD, MSCS, FAES

A recently conducted study found that treatment with cosyntropininjectable suspension was more effective than vigabatrin in children with infantile spasms syndrome.However, as the trial was underpowered due to incomplete enrollment resulting from cosyntropinavailability, investigators noted it necessitates an appropriately powered randomized control trial to evaluate combination therapy vs cosyntropin monotherapy.1

A total of 37 children between the age of 2 months and 2 years with new-onset infantile spasms syndrome and hypsarrhythmia were enrolled in the trial. Thirty-four were included in the final efficacy analysis after 1 child withdrew due to prior treatment and 2 children did not return seizure diaries.

Patients were randomized to 1 of 3 treatment arms to receive cosyntropin (n = 12), vigabatrin (n = 9), or a combination of consyntropin and vigabatrin (n = 13). Investigators, led by Kelly G. Knupp, MD, MSCS, FAES, associate professor ofpediatrics and neurology, and codirector, neurology research, University of Colorado, Anschutz Campus, in Aurora, Colorado, found that hypsarrhythmia and clinical spasms were resolved in 9 of 12 children treated with cosyntropin (75%), 1 of 9 treated with vigabatrin (11%), and 5 of 13 treated with combination therapy (38%). There primary comparison of cosyntropin and vigabratinwas statistically significant, with an effect size of 64% (P <.01), but there was no difference observed when comparing combination therapy and consyntropin monotherapy, with an effect size of –27% (P = .33).

“We did not expect to see such a large difference between children treated with vigabatrin and cosyntropin,” Knupp told NeurologyLive®. “We had hoped to see a difference between children treated with combination therapy and cosyntropin monotherapy—but it is important to note that enrollment was not complete, and we therefore need to be very cautious in interpreting these results.”

Children in all 3 treatment arms reported adverse events (AEs), with a total of 31 patients (86%) experiencing an AE, 7 patients (19%) experiencing a serious adverse event (SAE), and 15 patients (42%) experiencing an AE of special interest with no difference between treatment arms. SAEs attributable to treatment were lethargy, hypertension, acute respiratory failure, and sepsis, while SAEs not attributable to treatment were lethargy, vomiting, and bronchial infection. There were no changes in treatment due to AEs, and no deaths were reported in the study.

“These were typical of what has been reported in the literature and enforces that we need to counsel families of what to seek care for when children are on these medications,” Knupp said of the reported safety data.

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The study is the first to compare any formulation of adrenocorticotropic hormone and vigabatrin for treatment of infantile spasms syndrome in the US, including patients from 10 sites across the country. Included patients recorded daily seizures and AEs, and the primary outcome was seizure freedom for a 48-hour period prior to day 14, resolution of hypsarrhythmia on electroencephalogram at day 14, and absence of electrographic infantile spasms.

The study was limited due to the aforementioned incomplete enrollment. Additionally, the study design allowed providers to change management at 2 weeks of treatment, and the secondary endpoint was extended to 6 weeks.

“We would like to a see a study that has enrollment complete enough to assess a difference (or not) between combination therapy and cosyntropin monotherapy,” Knupp said, with investigators concluding that, according to data, the first-line treatment for these patients should be hormone therapy, except in instances where hormone therapy is contraindicated or refused or in patients with tuberous sclerosis complex, where vigabatrin should be used first.

“This study also demonstrated that US multicenter collaboration is possible, which is remarkable given the number of unanswered questions that remain for treatment of infantile spasms,” Knupp et al wrote. “An appropriately powered randomized control trial is needed to evaluate the efficacy and cost effectiveness of combination therapy compared to monotherapy and large, multicenter collaboration is possible to make this happen.”

1. Knupp KG, Coryell J, Singh RK, et al. Comparison of consyntropin, vigabatrin, and combination therapy in new-onset infantile spasms in a prospective randomized trial. Journal of Child Neurology. Published online January 19, 2022. doi:10.1177/08830738211073400

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