OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of hydroxyurea (HU) in spinal muscular atrophy (SMA) in a randomized, double-blind, placebo-controlled trial. METHODS:Twenty-eight patients with type 2 SMA and 29 patients with type3 SMA were randomly assigned (2:1) to receive HU or matching placebo for 18 months. HU was initiated at 10 mg/kg/day with an 8-week titration to 20 mg/kg/day. Subjects were assessed at baseline (T0) and monthly for the first 2 months (T1-T2) and then every 2 months throughout treatment (T3-T10) and posttreatment periods (T11-T13). The primary outcome measures were the Gross Motor Function Measure (GMFM), Manual Muscle Test (MMT), and serum full-length survivor motor neuron (flSMN) mRNA. The secondary outcome measures were Modified Hammersmith Functional Motor Scale and forced vital capacity (FVC). RESULTS:Fifty-five patients completed this trial, which lasted from March 2007 to June 2009. Except for neutropenia, we found no differences in adverse events between the 2 groups. Compared with the placebo group, the HU group had -1.88 for GMFM (p = 0.11), -0.55 for MMT (p = 0.49), and 2.17 for flSMN mRNA (p = 0.13). Similarly, we found no difference in mean improvement of the secondary endpoints. Both groups had a trend toward a decline in FVC with little change in strength and motor function. CONCLUSION: Under the current regimen and schedule, HU brought about no improvement in patients with type 2 and 3 SMA, and its main side effect was neutropenia. CLASSIFICATION OF EVIDENCE: This trial provides Class I evidence that HU 20 mg/kg/day does not effectively treat SMA.
RCT Entities:
OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of hydroxyurea (HU) in spinal muscular atrophy (SMA) in a randomized, double-blind, placebo-controlled trial. METHODS: Twenty-eight patients with type 2 SMA and 29 patients with type 3 SMA were randomly assigned (2:1) to receive HU or matching placebo for 18 months. HU was initiated at 10 mg/kg/day with an 8-week titration to 20 mg/kg/day. Subjects were assessed at baseline (T0) and monthly for the first 2 months (T1-T2) and then every 2 months throughout treatment (T3-T10) and posttreatment periods (T11-T13). The primary outcome measures were the Gross Motor Function Measure (GMFM), Manual Muscle Test (MMT), and serum full-length survivor motor neuron (flSMN) mRNA. The secondary outcome measures were Modified Hammersmith Functional Motor Scale and forced vital capacity (FVC). RESULTS: Fifty-five patients completed this trial, which lasted from March 2007 to June 2009. Except for neutropenia, we found no differences in adverse events between the 2 groups. Compared with the placebo group, the HU group had -1.88 for GMFM (p = 0.11), -0.55 for MMT (p = 0.49), and 2.17 for flSMN mRNA (p = 0.13). Similarly, we found no difference in mean improvement of the secondary endpoints. Both groups had a trend toward a decline in FVC with little change in strength and motor function. CONCLUSION: Under the current regimen and schedule, HU brought about no improvement in patients with type 2 and 3 SMA, and its main side effect was neutropenia. CLASSIFICATION OF EVIDENCE: This trial provides Class I evidence that HU 20 mg/kg/day does not effectively treat SMA.
Authors: Renske I Wadman; W Ludo van der Pol; Wendy Mj Bosboom; Fay-Lynn Asselman; Leonard H van den Berg; Susan T Iannaccone; Alexander Fje Vrancken Journal: Cochrane Database Syst Rev Date: 2020-01-06
Authors: Petra Kaufmann; Michael P McDermott; Basil T Darras; Richard S Finkel; Douglas M Sproule; Peter B Kang; Maryam Oskoui; Andrei Constantinescu; Clifton L Gooch; A Reghan Foley; Michele L Yang; Rabi Tawil; Wendy K Chung; William B Martens; Jacqueline Montes; Vanessa Battista; Jessica O'Hagen; Sally Dunaway; Jean Flickinger; Janet Quigley; Susan Riley; Allan M Glanzman; Maryjane Benton; Patricia A Ryan; Mark Punyanitya; Megan J Montgomery; Jonathan Marra; Benjamin Koo; Darryl C De Vivo Journal: Neurology Date: 2012-10-17 Impact factor: 9.910