Inexpensive Steroid 'Reasonable' Option for Infantile Spasms

Pauline Anderson

December 05, 2012

San Diego, California — A higher dose of an inexpensive and widely available steroid might be just as effective as a much more costly hormonal therapy for treating infantile spasms (IS), a small study suggests.

Results suggest that most babies with IS respond to a high dose of prednisolone, about 8 mg/kg/day to a maximum of about 60 mg. Although a larger study is needed to confirm this, organizing such a study might be something of an uphill battle, the researchers say.

"In the absence of a definitive trial, the treatment protocol presented here is a reasonable option," they conclude. Findings were presented here at the American Epilepsy Society (AES) 66th Annual Meeting.

Typically characterized by electrical abnormalities called hypsarrhythmia, with "subtle" seizure episodes often lasting only seconds and occurring in clusters, IS can be devastating if not adequately treated, study author Shaun Hussain, MD, assistant professor, pediatric neurology, Mattel Children's Hospital at the University of California, Los Angeles, told Medscape Medical News.

"These kids can be normal and then within a few months they're mentally retarded," said Dr. Hussain. He emphasized that he wants to use the phrase "mental retardation," defined by an IQ of 2 standard deviations below the mean, because it highlights the potential devastation linked to IS.

Drug Debate

Every year in the US, doctors see 2000 to 3000 new cases of IS, most of which occur in babies aged 4 to 8 months.

Specialists are divided on which drug best treats this condition — some believe that prednisolone, a generic drug prescribed for allergies and as an immunosuppressant, is preferable, whereas others lean toward adrenocorticotropin hormone (ACTH; Acthar, Questcor), now used to treat IS. The correct dosage for both drugs is also debatable.

Whereas prednisolone is widely available and taken in palatable liquid form, they point out, ACTH is a gel administered intramuscularly. A course of prednisolone costs about $200 compared with $125,000 for ACTH.

The new study included 30 babies with IS confirmed by overnight video electroencephalography (EEG), which captures the subtle seizures. The median age at IS onset was 6.5 months, and the median time to follow-up was 12.2 months.

The children were all treated with very-high-dose (8 mg/kg/day) prednisolone for 2 weeks. The response rate was 60%, a rate that, according to Dr. Hussain, is significantly higher than in previous studies using traditional doses of prednisolone (2 mg/kg/day).

Babies were considered to have responded if they had no electrical abnormalities or spasms. This was confirmed through another session of video EEG.

All or None

"We think it's an all or none phenomenon, that you have to have a complete response to give these kids a chance for good development," said Dr. Hussain.

Nonresponders to this prednisolone regimen were given ACTH (150 IU/m2/day), and of these, 42% responded.

"That suggests either than ACTH is better, or maybe you just need some form of hormonal therapy for a course longer than 2 weeks," said Dr. Hussain. "We need a big study to figure that out; otherwise, we may be wasting a lot of money on ACTH or we might not be giving kids a chance with ACTH."

Such a trial might be difficult to organize without the input from the drug manufacturer. "But in the interests of patients and healthcare spending and the health system in general, I think this study has to be done," said Dr. Hussain.

In this current study, the relapse rate was 11% after initial prednisolone response and 40% after ACTH initial response.

Both drugs are associated with an array of adverse events. "Kids are routinely irritable and they gain weight," he noted. ACTH injections can also be painful, said Dr. Hussain. Because both agents suppress the immune system, serious infections are also a concern.

IS, which can be caused by a tumor, stoke, genetic disorder, or structural malformation, is often missed by healthcare professionals: The subtle eye movements of babies are often attributed to something else.

Dr. Hussain has served on the advisory board for Questcor and has received a small grant from a competing company (which manufactures vigabatrin [Sabril]).

American Epilepsy Society (AES) 66th Annual Meeting. Abstract 1.247. Presented December 3, 2012.