Prednisolone or tetracosactide depot for infantile epileptic spasms syndrome? A prospective analysis of data embedded within two randomised controlled trials

• Published in: European journal of paediatric neurology Vol. 42; pp. 110 - 116
• Main Authors: Osborne, John P., Edwards, Stuart W., Alber, Fabienne Dietrich, Hancock, Eleanor, Johnson, Anthony L., Kennedy, Colin R., Likeman, Marcus, Lux, Andrew L., Mackay, Mark, Mallick, Andrew, Newton, Richard W., Nolan, Melinda, Pressler, Ronit, Rating, Dietz, Schmitt, Bernhard, Verity, Christopher M., O'Callaghan, FinbarJ.K.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2023
• Subjects: Anticonvulsants - therapeutic use; Cosyntropin - therapeutic use; Epilepsy - drug therapy; Epileptic spasms; Humans; Infant; Infantile epileptic spasm syndrome; Infantile spasms; International collaborative infantile spasms study; Prednisolone; Prednisolone - therapeutic use; Randomised controlled trial; Randomized Controlled Trials as Topic; Spasm; Spasms, Infantile - drug therapy; Syndrome; Tetracosactide; Treatment Outcome; United Kingdom Infantile spasms study; Vigabatrin - therapeutic use; West syndrome; West syndrome; Infantile spasms; Randomised controlled trial; Infantile epileptic spasm syndrome; Tetracosactide; United Kingdom Infantile spasms study; International collaborative infantile spasms study; Epileptic spasms; Prednisolone
• ISSN: 1090-3798; 1532-2130
• DOI: 10.1016/j.ejpn.2022.12.007

To report a prospectively planned analysis of two randomised controlled trials with embedded comparisons of prednisolone versus tetracosactide depot for the treatment of infantile epileptic spasms syndrome (IESS). Individual patient data from patients randomly allocated to prednisolone or tetracosactide depot were analysed from two trials (UKISS, ICISS). The comparison was embedded within trials in which some patients also received vigabatrin but only patients receiving monotherapy with randomly allocated hormonal treatments are included in this analysis. The main outcome was cessation of spasms (Days 13–14 after randomisation). Lead time to treatment and underlying aetiology were taken into account. Cessation of spasms on Days 14–42 inclusive, electroclinical response (EEG Day 14), plus developmental and epilepsy outcomes (at 14 months in UKISS and 18 months in ICISS) are also reported. Minimum treatment was prednisolone 40 mg per day for two weeks or tetracosactide depot 0·5 mg IM on alternate days for two weeks, all followed by a reducing dose of prednisolone over two weeks. 126 infants were included in this study. On tetracosactide depot, 47 of 62 (76%) were free of spasms on Days 13–14 compared to 43 of 64 (67%) on prednisolone (difference 9%, 95% CI -7·2% to +25·2%, chi square 1·15, p = 0·28). For Day 14–42 cessation of spasms, on tetracosactide depot, 41 of 61 (67%) were free of spasms compared to 35 of 62 (56%) on prednisolone (difference 11%, 95% CI -6·4% to +28·4%, chi square 1·51, p = 0·22). There was no significant difference in mean VABS score between infants who received prednisolone compared with those who received tetracosactide depot (74·8 (SD 18·3) versus 78·0 (SD 20·2) t = −0·91 p = 0·36). The proportion with ongoing epilepsy at the time of developmental assessment was 20 of 61 (33%) in the tetracosactide group compared with 26 out of 63 (41%) in the prednisolone group (difference 8%, 95% CI -9·2% to +25·2%, Chi [2] 0·95, p = 0·33). With hormone monotherapy, either prednisolone or tetracosactide depot may be recommended for infantile epileptic spasms syndrome. •Embedding a second randomisation in trials effectively provides additional information about trial treatments.•There was no significant difference between prednisolone and tetracosactide depot in those achieving early spasm cessation.•There was no significant difference between trial treatments in those free of epileptic seizures at 14 and 18 months.•Developmental outcome was similar in both treatment groups.•Either prednisolone or tetracosactide depot can be recommended when using hormonal treatment as monotherapy.