Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort

Abstract

Objective 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. Methods 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. Results 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). Significance 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.

Treatment of infantile spasms

“…(1) Even if combination therapy is superior to hormonal monotherapy, is it also superior to sequential therapy (e.g., ACTH or prednisolone × 14 days followed by optional VGB × 14 days) with outcome assessed at day 28? Indeed, limited observational data suggest that substantial response accompanies the use of VGB after hormonal therapy failure, as well as hormonal therapy following VGB failure . Similarly, in the study of Ko and colleagues, initial response to VGB monotherapy was modest, and cumulative response to add‐on high‐dose prednisolone was excellent .…”

Efficacy and tolerability of the ketogenic diet versus high‐dose adrenocorticotropic hormone for infantile spasms: A single‐center parallel‐cohort randomized controlled trial

“…Although epileptic spasms and hypsarrhythmia resolve with time, many children develop other forms of drug-resistant epilepsy syndromes, and severe intellectual disabilities are shown in about 70%. [5][6][7] However, only ACTH treatment has class I evidence; therefore, it is the primary treatment option. Furthermore, the investigated drugs have frequently been started long after disease onset and in combination with or after multiple other antiepileptic drugs (AEDs).…”

Should you Use ACTH or Vigabatrin for Infantile Spasms? Or Why Not Use Both Together?

“…Infants with cryptogenic etiology receiving hormonal treatment had higher developmental scores than those receiving VGB; 3. The NISC studies were not sufficiently powered to detect differences between various nonstandard treatments 3,4 . Published reports suggest that some therapies (ketogenic diet, valproate, topiramate) may be more effective than others such as phenobarbital, oxcarbazepine, or pyridoxine (at least in North America);…”

“…An update to these guidelines may be needed in light of newly published data including the study cited above.The National Infantile Spasms Consortium (NISC) recruited 230 children with infantile spasms from 22 US centers in a prospective study to assess early and sustained response to hormonal treatments (ACTH, oral steroids), VGB, and other treatments designated as nonstandard therapy 3,4 . Unlike the United Kingdom Infantile Spasm Study (UKISS), children with tuberous sclerosis (TS) were not excluded 5 .…”