High-dose Corticotropin (ACTH) Versus Prednisone for Infantile Spasms: A Prospective, Randomized, Blinded Study

Abstract

Objective. To compare the efficacy of corticotropin (ACTH) (150 U/m2/day) and prednisone (2 mg/kg/day), given for 2 weeks, in suppressing clinical spasms and hypsarrhythmic electroencephalogram (EEG) in infantile spasms (IS). ACTH and prednisone are standard treatments for IS. ACTH at high doses causes severe dose- and duration-dependent side effects, but may be superior to prednisone, based on retrospective or uncontrolled studies. Blinded prospective studies have shown equal efficacy of prednisone and low-dose ACTH, and low versus high-dose ACTH. Design. A prospective, randomized, single-blinded study. Subjects and Methods. Patient population consisted of consecutive infants fulfilling entry criteria, including the presence of clinical spasms, hypsarrhythmia (or variants) during a full sleep cycle video-EEG, and no prior steroid/ACTH treatment. Response required both cessation of spasms and elimination of hypsarrhythmia by the end of the 2-week treatment period, as determined by an investigator "blinded" to treatment. Treatment of responders was tapered off over 12 days; those failing one hormone were crossed-over to the other. Results. Of 34 eligible infants, 29 were enrolled. Median age of patients was 6 months. Twenty-two infants were "symptomatic" with known or suspected cause, and seven were cryptogenic (two normal). Of 15 infants randomized to ACTH, 13 responded by both EEG and clinical criteria (86.6%); seizures stopped in an additional infant, but EEG remained hypsarrhythmic (considered a failure). Four of 14 patients given prednisone responded (28.6%, with complete clinical-EEG correlation), significantly less than with ACTH, (x2 test). Conclusions. Using a prospective, randomized approach, a 2-week course of high-dose ACTH is superior to 2 weeks of prednisone for treatment of IS, as assessed by both clinical and EEG criteria.

Effectiveness of ACTH in Patients with Infantile Spasms

“…In addition, clobazam used in our study might be a potentially effective adjunctive drug for West syndrome [37]. It is worth mentioning that similar results were reached in some old studies in the case of highdose ACTH monotherapy and combination of low-dose ACTH and pyridoxine [23,38]. According to some authors, increasing the dose of ACTH does not necessarily result in better seizures control [39].…”

Hormonal Therapy for Infantile Spasms: A Systematic Review and Meta-Analysis

“…Six RCTs that compared ACTH with oral corticosteroids for the treatment of ISs, with 323 participants included, met our inclusion criteria ( 5 , 7 , 9 , 11 , 12 , 15 ). Three of these RCTs, namely, Hrachovy et al ( 5 ), Baram et al ( 7 ), and Sardar et al ( 15 ), used low-dose corticosteroids (2 mg/kg/day of prednisone or prednisolone). The other three RCTs, namely, Lux et al ( 9 ), Wanigasinghe et al ( 11 ), and Gowda et al ( 12 ), applied high-dose prednisolone (4 mg/kg/day or 40–60 mg/day).…”

“…Six RCTs that compared ACTH with oral corticosteroids for the treatment of ISs, with 323 participants included, met our inclusion criteria (5,7,9,11,12,15). Three of these RCTs, namely, Hrachovy et al 9) was between hormonal therapy and VGB, so the secondary comparison of ACTH and prednisolone might be underpowered.…”

“…However, hormonal therapy is partially effective. The responder rate of hormonal therapy varied from 37 to 87%, and the relapse rate can be up to 66% (5)(6)(7)(8)(9)(10)(11)(12). Therefore, other treatments, including antiepileptic drugs (AEDs) and the ketogenic diet (KD), are also actively investigated.…”

Comparison of Efficacy and Safety of Low- Versus High-Dose Oral Prednisolone in Infantile Spasm (IS): An Open Label Randomized Controlled Trial at the Children’s Hospital & Institute of Child Health, Multan, Pakistan

“…In the present study, overall efficacy in terms of complete response of prednisolone was observed in 43.5% of the total cases. Complete spasm freedom rates have been reported between 28% and 49% by different researchers with various dosage regimens of prednisolone [ 19 , 20 ]. We noted that infants in the high-dose group reported significantly better efficacy when compared to the low-dose group (complete response as 58.1% vs. 29.0%, p=0.0265).…”