Efficacy of risdiplam in spinal muscular atrophy: A systematic review and meta‐analysis

Abstract

ObjectivesThis systematic review and meta‐analysis aimed to assess the efficacy and safety of risdiplam on motor and respiratory function in spinal muscular atrophy (SMA).MethodsWe systematically searched Medline, Scopus, Web of Science, and the Cochrane Library from inception to March 2023. We included pre‐post studies that determined the effect of risdiplam on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP‐INTEND), the 32‐item Motor Function Measure (MFM32), the Revised upper limb module (RULM), the Hammersmith Functional Motor Scale ‐ Expanded (HFMSE), respiratory function, and the proportion of risdiplam‐related adverse events in a population with SMA (phenotypes 1 and 2/3). Meta‐analyses were also performed where possible.ResultsEleven studies were included. After 12 months of treatment, 57% of participants with SMA1 achieved a CHOP‐INTEND score ≥40 points, and more than half were able to feed orally and had head control. In SMA2/3, MFM32, RULM, and HFMSE increased by 2.09 (1.17, 3.01), 1.73 (1.25, 2.20), and 1.00 (0.40, 1.59) points, respectively. Efficacy on respiratory function in SMA2/3 was inconsistent. Finally, 16% of participants experienced adverse events, but serious adverse events could not be quantified due to a lack of cases.ConclusionThe limited available evidence suggests that risdiplam is an effective and safe drug for the treatment of SMA. In addition, long‐term clinical benefit may be partly determined by the stage of disease at which treatment is initiated.

Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy

“… 81 A more recent publication of a systematic review and metanalysis study reported that after 12 months of treatment with risdiplam, 57% of participants with SMA type 1 achieved a CHOP-INTEND score ≥ 40 points, and more than half were able to feed orally and had head control. 85 In SMA types 2 and 3, MFM32, RULM, and HFMSE increased by 2.09, 1.73, and 1.00 points, respectively. 85 …”

“… 85 In SMA types 2 and 3, MFM32, RULM, and HFMSE increased by 2.09, 1.73, and 1.00 points, respectively. 85 …”

Multidisciplinary team meetings in treatment of spinal muscular atrophy adult patients: a real-life observatory for innovative treatments

“…In a monocentric longitudinal cohort study, HFMSE and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores increased in parallel with increases of CMAP amplitudes in both median nerves in 18 adult patients with SMA type 2 or 3 treated with risdiplam during a 10-month treatment period [ 23 ]. Observational studies, meta-analysis and real life will likely define its therapeutic effect in adult patients [ 24 – 26 ].…”

Gene-based therapies for neuromuscular disorders

“…48 Real-world experience with risdiplam has also been published and further supported its beneficial effects on motor function in patients with SMA. 49 RAINBOWFISH is an ongoing, multicenter, open-label, single-arm study to assess the efficacy and safety of risdiplam in pre-symptomatic SMA. Preliminary data showed that most infants treated with risdiplam could sit independently, and many were standing and walking as assessed by the HINE-2 at month 12.…”

“… 48 Real-world experience with risdiplam has also been published and further supported its beneficial effects on motor function in patients with SMA. 49 …”