Editors' Note: Nusinersen in Adult Patients With Spinal Muscular Atrophy: Observations From a Single Center

Abstract

In “Nusinersen in Adult Patients With Spinal Muscular Atrophy: Observations From a Single Center,” Moshe-Lilie et al. compared 10 adult patients with spinal muscular atrophy (SMA) treated with nusinersen for 6–24 months with 12 untreated patients. They found that although half of the treated patients endorsed subjective improvement, there was no evidence of objective improvement, and half of the treated patients experienced side effects. The authors concluded that decision making about the use of nusinersen in adult patients with SMA requires careful consideration because the benefit is unclear; there is a risk of side effects, some of which can be serious; and the cost is substantial. Hagenacker et al. believed that this conclusion was premature given (1) the small size of this study; (2) the methods included evaluation of strength using the Medical Research Council (MRC) scores, which they felt were antiquated and no longer considered an acceptable way to assess muscle function in such patients; (3) the number of serious adverse events experienced by patients in this study was unusually high; and (4) larger studies demonstrated the benefit of nusinersen on motor function in this patient population. Karam et al. responded that (1) the MRC scores were the only tool used consistently in this retrospective study; (2) clinical improvement, which should be evident on any scale, was not seen in their patients; (3) the side effects their patients experienced have been described elsewhere; and (4) larger studies were not published before their article was submitted. Furthermore, they noted that an important weakness of the existing larger studies is the lack of a placebo group and emphasized the need for a randomized double-blind placebo control trial to more clearly evaluate the benefits and risks of nusinersen in adults with SMA. In “Nusinersen in Adult Patients With Spinal Muscular Atrophy: Observations From a Single Center,” Moshe-Lilie et al. compared 10 adult patients with spinal muscular atrophy (SMA) treated with nusinersen for 6–24 months with 12 untreated patients. They found that although half of the treated patients endorsed subjective improvement, there was no evidence of objective improvement, and half of the treated patients experienced side effects. The authors concluded that decision making about the use of nusinersen in adult patients with SMA requires careful consideration because the benefit is unclear; there is a risk of side effects, some of which can be serious; and the cost is substantial. Hagenacker et al. believed that this conclusion was premature given (1) the small size of this study; (2) the methods included evaluation of strength using the Medical Research Council (MRC) scores, which they felt were antiquated and no longer considered an acceptable way to assess muscle function in such patients; (3) the number of serious adverse events experienced by patients in this study was unusually high; and (4) larger studies demonstrated the benefit of nusinersen on motor function in this patient population. Karam et al. responded that (1) the MRC scores were the only tool used consistently in this retrospective study; (2) clinical improvement, which should be evident on any scale, was not seen in their patients; (3) the side effects their patients experienced have been described elsewhere; and (4) larger studies were not published before their article was submitted. Furthermore, they noted that an important weakness of the existing larger studies is the lack of a placebo group and emphasized the need for a randomized double-blind placebo control trial to more clearly evaluate the benefits and risks of nusinersen in adults with SMA.