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

John P. Osborne; Stuart W. Edwards; Fabienne Dietrich Alber; Eleanor Hancock; Anthony L. Johnson; Colin R. Kennedy; Marcus Likeman; Andrew L. Lux; Mark Mackay; Andrew Mallick; Richard W. Newton; Melinda Nolan; Ronit Pressler; Dietz Rating; Bernhard Schmitt; Christopher M. Verity; Finbar J. K. O'Callaghan

doi:10.1016/j.ejpn.2022.12.007

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

John P. Osborne, Stuart W. Edwards, Fabienne Dietrich Alber, Eleanor Hancock, Anthony L. Johnson, Colin R. Kennedy, Marcus Likeman, Andrew L. Lux, Mark Mackay, Andrew Mallick, Richard W. Newton, Melinda Nolan, Ronit Pressler, Dietz Rating, Bernhard Schmitt, Christopher M. Verity, Finbar J. K. O'Callaghan

Department for Health

Research output: Contribution to journal › Article › peer-review

2 Citations (SciVal)

Abstract

Objective: 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). Methods: 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. Results: 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). Significance: With hormone monotherapy, either prednisolone or tetracosactide depot may be recommended for infantile epileptic spasms syndrome.

Original language	English
Pages (from-to)	110-116
Number of pages	7
Journal	European Journal of Paediatric Neurology
Volume	42
Early online date	26 Dec 2022
DOIs	https://doi.org/10.1016/j.ejpn.2022.12.007
Publication status	Published - 31 Jan 2023

Bibliographical note

Funding Information:
Although they have been acknowledged and thanked in earlier publications, we thank again sincerely all those involved in the trials analysed for this study but in particular the parents, the infants and the clinicians who took part in the trials. The clinicians are named in earlier publications – see http://image.thelancet.com/extras/03art11384webappendix.pdf and https://doi.org/10.1016/S1474-4422(16)30294-0 . We must also thank those providing funding, in particular the Bath Unit for Research in Paediatrics, the Castang Foundation, the BRONNER-BENDER Stiftung/Gernsbach, the University Children's Hospital Zurich, Bishopsgate financial management, the Wellcome Trust and Cow and Gate Ltd .

Funding Information:
JPO unsuccessfully approached Aventis for funding of a follow up study to look at visual field defects: he appeared in a promotional video for Aventis: he received income from UCB Pharma. The study sponsor for UKISS and ICISS received funding from Marathon and from UCB Pharma which was used in part to fund the research reported including salaries to JPO and SE. JPO, SE, FJKOC, EH and AL all received IP payments from the sponsor relating to funding from Marathon. AL received funding from Hoechst-Marion-Roussel to attend a conference. No other authors declared a conflict of interest.Although they have been acknowledged and thanked in earlier publications, we thank again sincerely all those involved in the trials analysed for this study but in particular the parents, the infants and the clinicians who took part in the trials. The clinicians are named in earlier publications – see http://image.thelancet.com/extras/03art11384webappendix.pdf and https://doi.org/10.1016/S1474-4422(16)30294-0. We must also thank those providing funding, in particular the Bath Unit for Research in Paediatrics, the Castang Foundation, the BRONNER-BENDER Stiftung/Gernsbach, the University Children's Hospital Zurich, Bishopsgate financial management, the Wellcome Trust and Cow and Gate Ltd.

Funding

Although they have been acknowledged and thanked in earlier publications, we thank again sincerely all those involved in the trials analysed for this study but in particular the parents, the infants and the clinicians who took part in the trials. The clinicians are named in earlier publications – see http://image.thelancet.com/extras/03art11384webappendix.pdf and https://doi.org/10.1016/S1474-4422(16)30294-0 . We must also thank those providing funding, in particular the Bath Unit for Research in Paediatrics, the Castang Foundation, the BRONNER-BENDER Stiftung/Gernsbach, the University Children's Hospital Zurich, Bishopsgate financial management, the Wellcome Trust and Cow and Gate Ltd . JPO unsuccessfully approached Aventis for funding of a follow up study to look at visual field defects: he appeared in a promotional video for Aventis: he received income from UCB Pharma. The study sponsor for UKISS and ICISS received funding from Marathon and from UCB Pharma which was used in part to fund the research reported including salaries to JPO and SE. JPO, SE, FJKOC, EH and AL all received IP payments from the sponsor relating to funding from Marathon. AL received funding from Hoechst-Marion-Roussel to attend a conference. No other authors declared a conflict of interest.Although they have been acknowledged and thanked in earlier publications, we thank again sincerely all those involved in the trials analysed for this study but in particular the parents, the infants and the clinicians who took part in the trials. The clinicians are named in earlier publications – see http://image.thelancet.com/extras/03art11384webappendix.pdf and https://doi.org/10.1016/S1474-4422(16)30294-0. We must also thank those providing funding, in particular the Bath Unit for Research in Paediatrics, the Castang Foundation, the BRONNER-BENDER Stiftung/Gernsbach, the University Children's Hospital Zurich, Bishopsgate financial management, the Wellcome Trust and Cow and Gate Ltd.

Keywords

Epileptic spasms
Infantile epileptic spasm syndrome
Infantile spasms
International collaborative infantile spasms study
Prednisolone
Randomised controlled trial
Tetracosactide
United Kingdom Infantile spasms study
West syndrome

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Clinical Neurology

Access to Document

10.1016/j.ejpn.2022.12.007Licence: CC BY

Cite this

Osborne, J. P., Edwards, S. W., Alber, F. D., Hancock, E., Johnson, A. L., Kennedy, C. R., Likeman, M., Lux, A. L., Mackay, M., Mallick, A., Newton, R. W., Nolan, M., Pressler, R., Rating, D., Schmitt, B., Verity, C. M., & O'Callaghan, F. J. K. (2023). Prednisolone or tetracosactide depot for infantile epileptic spasms syndrome? A prospective analysis of data embedded within two randomised controlled trials. European Journal of Paediatric Neurology, 42, 110-116. https://doi.org/10.1016/j.ejpn.2022.12.007

Prednisolone or tetracosactide depot for infantile epileptic spasms syndrome? A prospective analysis of data embedded within two randomised controlled trials. / Osborne, John P.; Edwards, Stuart W.; Alber, Fabienne Dietrich et al.
In: European Journal of Paediatric Neurology, Vol. 42, 31.01.2023, p. 110-116.

Research output: Contribution to journal › Article › peer-review

Osborne, JP, Edwards, SW, Alber, FD, Hancock, E, Johnson, AL, Kennedy, CR, Likeman, M, Lux, AL, Mackay, M, Mallick, A, Newton, RW, Nolan, M, Pressler, R, Rating, D, Schmitt, B, Verity, CM & O'Callaghan, FJK 2023, 'Prednisolone or tetracosactide depot for infantile epileptic spasms syndrome? A prospective analysis of data embedded within two randomised controlled trials', European Journal of Paediatric Neurology, vol. 42, pp. 110-116. https://doi.org/10.1016/j.ejpn.2022.12.007

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

abstract = "Objective: 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). Methods: 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. Results: 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). Significance: With hormone monotherapy, either prednisolone or tetracosactide depot may be recommended for infantile epileptic spasms syndrome.",

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author = "Osborne, {John P.} and Edwards, {Stuart W.} and Alber, {Fabienne Dietrich} and Eleanor Hancock and Johnson, {Anthony L.} and Kennedy, {Colin R.} and Marcus Likeman and Lux, {Andrew L.} and Mark Mackay and Andrew Mallick and Newton, {Richard W.} and Melinda Nolan and Ronit Pressler and Dietz Rating and Bernhard Schmitt and Verity, {Christopher M.} and O'Callaghan, {Finbar J. K.}",

note = "Funding Information: Although they have been acknowledged and thanked in earlier publications, we thank again sincerely all those involved in the trials analysed for this study but in particular the parents, the infants and the clinicians who took part in the trials. The clinicians are named in earlier publications – see http://image.thelancet.com/extras/03art11384webappendix.pdf and https://doi.org/10.1016/S1474-4422(16)30294-0 . We must also thank those providing funding, in particular the Bath Unit for Research in Paediatrics, the Castang Foundation, the BRONNER-BENDER Stiftung/Gernsbach, the University Children's Hospital Zurich, Bishopsgate financial management, the Wellcome Trust and Cow and Gate Ltd . Funding Information: JPO unsuccessfully approached Aventis for funding of a follow up study to look at visual field defects: he appeared in a promotional video for Aventis: he received income from UCB Pharma. The study sponsor for UKISS and ICISS received funding from Marathon and from UCB Pharma which was used in part to fund the research reported including salaries to JPO and SE. JPO, SE, FJKOC, EH and AL all received IP payments from the sponsor relating to funding from Marathon. AL received funding from Hoechst-Marion-Roussel to attend a conference. No other authors declared a conflict of interest.Although they have been acknowledged and thanked in earlier publications, we thank again sincerely all those involved in the trials analysed for this study but in particular the parents, the infants and the clinicians who took part in the trials. The clinicians are named in earlier publications – see http://image.thelancet.com/extras/03art11384webappendix.pdf and https://doi.org/10.1016/S1474-4422(16)30294-0. We must also thank those providing funding, in particular the Bath Unit for Research in Paediatrics, the Castang Foundation, the BRONNER-BENDER Stiftung/Gernsbach, the University Children's Hospital Zurich, Bishopsgate financial management, the Wellcome Trust and Cow and Gate Ltd. ",

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T1 - Prednisolone or tetracosactide depot for infantile epileptic spasms syndrome? A prospective analysis of data embedded within two randomised controlled trials

AU - Osborne, John P.

AU - Edwards, Stuart W.

AU - Alber, Fabienne Dietrich

AU - Hancock, Eleanor

AU - Johnson, Anthony L.

AU - Kennedy, Colin R.

AU - Likeman, Marcus

AU - Lux, Andrew L.

AU - Mackay, Mark

AU - Mallick, Andrew

AU - Newton, Richard W.

AU - Nolan, Melinda

AU - Pressler, Ronit

AU - Rating, Dietz

AU - Schmitt, Bernhard

AU - Verity, Christopher M.

AU - O'Callaghan, Finbar J. K.

N1 - Funding Information: Although they have been acknowledged and thanked in earlier publications, we thank again sincerely all those involved in the trials analysed for this study but in particular the parents, the infants and the clinicians who took part in the trials. The clinicians are named in earlier publications – see http://image.thelancet.com/extras/03art11384webappendix.pdf and https://doi.org/10.1016/S1474-4422(16)30294-0 . We must also thank those providing funding, in particular the Bath Unit for Research in Paediatrics, the Castang Foundation, the BRONNER-BENDER Stiftung/Gernsbach, the University Children's Hospital Zurich, Bishopsgate financial management, the Wellcome Trust and Cow and Gate Ltd . Funding Information: JPO unsuccessfully approached Aventis for funding of a follow up study to look at visual field defects: he appeared in a promotional video for Aventis: he received income from UCB Pharma. The study sponsor for UKISS and ICISS received funding from Marathon and from UCB Pharma which was used in part to fund the research reported including salaries to JPO and SE. JPO, SE, FJKOC, EH and AL all received IP payments from the sponsor relating to funding from Marathon. AL received funding from Hoechst-Marion-Roussel to attend a conference. No other authors declared a conflict of interest.Although they have been acknowledged and thanked in earlier publications, we thank again sincerely all those involved in the trials analysed for this study but in particular the parents, the infants and the clinicians who took part in the trials. The clinicians are named in earlier publications – see http://image.thelancet.com/extras/03art11384webappendix.pdf and https://doi.org/10.1016/S1474-4422(16)30294-0. We must also thank those providing funding, in particular the Bath Unit for Research in Paediatrics, the Castang Foundation, the BRONNER-BENDER Stiftung/Gernsbach, the University Children's Hospital Zurich, Bishopsgate financial management, the Wellcome Trust and Cow and Gate Ltd.

PY - 2023/1/31

Y1 - 2023/1/31

N2 - Objective: 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). Methods: 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. Results: 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). Significance: With hormone monotherapy, either prednisolone or tetracosactide depot may be recommended for infantile epileptic spasms syndrome.

AB - Objective: 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). Methods: 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. Results: 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). Significance: With hormone monotherapy, either prednisolone or tetracosactide depot may be recommended for infantile epileptic spasms syndrome.

KW - Epileptic spasms

KW - Infantile epileptic spasm syndrome

KW - Infantile spasms

KW - International collaborative infantile spasms study

KW - Prednisolone

KW - Randomised controlled trial

KW - Tetracosactide

KW - United Kingdom Infantile spasms study

KW - West syndrome

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DO - 10.1016/j.ejpn.2022.12.007

M3 - Article

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AN - SCOPUS:85145994807

SN - 1090-3798

VL - 42

SP - 110

EP - 116

JO - European Journal of Paediatric Neurology

JF - European Journal of Paediatric Neurology

ER -

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

Abstract

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