Response to sequential treatment with prednisolone and vigabatrin in infantile spasms

Abstract

Aim: To report response to first treatment in infants with infantile spasms (IS), including incremental benefit of prednisolone 60 mg/day and vigabatrin following prednisolone 40 mg/day failure in infants commenced on the United Kingdom Infantile Spasms Study (UKISS) treatment sequence. Methods: In this retrospective analysis, we compared effectiveness of prednisolone, vigabatrin and nonstandard treatments as first treatment for IS. In infants who commenced the UKISS treatment sequence, we evaluated response to each step. Primary outcome was spasm cessation after 42 days. Secondary outcomes were severe side effects and spasm relapse after 42 days. Results: Treatment response data were available for 151 infants. First treatment was prednisolone in 99 infants, vigabatrin in 18 and nonstandard treatment in 34. The rate of spasm cessation with first treatment was significantly higher with prednisolone (62/99, 63%) than vigabatrin (5/18, 28%, P = 0.01) or nonstandard treatment (2/34, 5.9%, P < 0.01). Of 112 infants who commenced the UKISS treatment sequence, 71/112 (63%) responded to prednisolone 40 mg/day. Among non-responders, 12/29 (41%) subsequently responded to prednisolone 60 mg/day, and 10/22 (45%) to vigabatrin. Severe side effects and spasm relapse were not significantly different between each treatment. Conclusion: We confirm higher rates of spasm cessation with initial treatment with prednisolone than vigabatrin and nonstandard therapy. Non-use of prednisolone as first treatment in over one third of infants highlights a concerning treatment gap. The UKISS treatment sequence has high overall treatment response (total 93/112; 83%), with similar benefit of subsequent prednisolone 60 mg/day and vigabatrin in prednisolone 40 mg/day non-responders.

Efficacy of vigabatrin in the treatment of infantile epileptic spasms syndrome: A systematic review and meta‐analysis

“…Meta‐analysis of the nine OSs 21,26,28–30,32–34,40 also revealed that hormonal therapy was more effective than VGB for IESS (OR = 0.61, 95% CI = 0.43‐0.85, P = 0.0037), with low heterogeneity ( I 2 = 13%) between these studies (Figure 2B). The sensitivity analysis suggested that excluding either study did not change the original result (Figure 3B).…”

“…So we excluded three of the trials and included the latest study by Yuskaitis et al 21 with the largest number of patients. Finally, 20 studies 21,26–44 . appropriately covered the topics, met the eligibility criteria, and were included in this review.…”

“…The details of the 20 included articles are listed in Tables 1 and 2. Six RCTs and 14 OSs, including 2225 patients (1261 males, 56.7%), were published between 1996 and 2022 21,26–44 . Fourteen trials (five RCTs and nine OSs) 21,26–30,32–37,40,43 compared the efficacy of VGB vs hormonal monotherapy for IESS.…”

“…Finally, 20 studies. 21,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] appropriately covered the topics, met the eligibility criteria, and were included in this review.…”

“…Six RCTs and 14 OSs, including 2225 patients (1261 males, 56.7%), were published between 1996 and 2022. 21,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] Fourteen trials (five RCTs and nine OSs) 21,[26][27][28][29][30][32][33][34][35][36][37]40,43 compared the efficacy of VGB vs hormonal monotherapy for IESS. The five RCTs 27,[35][36][37]43 comparing the efficacy of VGB vs hormonal monotherapy involved 211 patients, of whom 106 were treated with VGB and 105 with hormonal therapy.…”