Two-year placebo-controlled trial of botulinum toxin A for leg spasticity in cerebral palsy

Background: The controlled evidence favoring botulinum toxin A (BtA) treatment for spasticity in cerebral palsy is based on short-term studies. Methods: We conducted a randomized, double-blind, placebo-controlled, parallel-group study of BtA (Dysport) for leg spasticity in 64 children with cerebral palsy. For 2 years, the children received trial injections of up to 30 mu/kg every 3 months if clinically indicated. Results: For the primary endpoints of Gross Motor Function Measure (GMFM) and Pediatric Evaluation of Disability Index (PEDI) scaled scores at 2 years (trough rather than peak effect), there were no differences between the mean change scores of each group. For the GMFM total score, the 95% CI of - 4.81 to 1.90 excluded a 5-point difference in either direction, and a 2-point benefit with 95% confidence. There were no differences in adverse events. Conclusions: There was no evidence of cumulative or persisting benefit from repeated botulinum toxin A (BtA) at the injection cycle troughs at 1 year or 2 years. The dose was not enough to change spasticity measures and thus GMFM in this heterogeneous group. Ceiling effects in GMFM and Pediatric Evaluation of Disability Index (PEDI) may have reduced responsiveness. This finding does not deny the value, individually, of single injection cycles or prove that repeating them is unhelpful. In this regard, BtA treatment can be viewed in the same light as other temporary measures to relieve spasticity, such as oral or intrathecal agents: there is no evidence of continuing benefit if the treatment ceases. The study provides long-term, fully controlled adverse event data and has not revealed any long-term adverse effects.