Do we always need to treat patients with spinal muscular atrophy? A personal view and experience

Abstract

Background We report the clinical outcomes observed in our patients with SMA type 1 or 2 receiving nusinersen, and we comment on the ethical implications of this treatment, in line with our results and those reported by Audic et al. in their analysis published in the Orphanet Journal of Rare Diseases. Methods We analyzed records of all children with a genetically diagnosed SMA and clinically confirmed diagnosis of SMA Type 1 or 2 to whom nusinersen was offered. Follow-up lasted 30 months. Results Among the 17 children with SMA type 1, 6 interrupted treatment with nusinersen due to adverse events or lack of efficacy. Of the remaining 11 patients, 9 are responding to therapy, though multidisciplinary complex care is still required. All those children started nusinersen at a very early age. Eighteen patients with SMA type 2 received nusinersen; five required treatment interruption. The other 13 patients are still on nusinersen therapy, and 6 are responders. Among the seven non-responders, only two met the inclusion criteria of the pivotal trial. Conclusions Our analysis further supports the findings reported in the study by Audic et al. We believe that a wider use of nusinersen in clinical practice would require a comprehensive assessment of its actual benefits weighed against the discomfort caused to patients, as well as the identification of the patients who may obtain the best benefits from this treatment.

Quality of Life Outcomes According to Differential Nusinersen Exposure in Pediatric Spinal Muscular Atrophy

“…Further, concerns persisted that nusinersen could not be approved or that the child could be excluded due to an insufficient treatment response” [ 26 ]. While medical teams may consider nusinersen generally well tolerated and efficacious, parents depict worry about their child not responding to nusinersen, requiring treatment interruptions, and experiencing complications [ 39 ].…”

How children and caregivers viewed the change from nusinersen to risdiplam for treating spinal muscular atrophy

“…It has been very difficult to manage the high expectations that patients and families have had for nusinersen, and this has led to disappointment, frustration and discontinued treatment. 3 We provided extensive information about the possibility of switching to enteral treatment for patients with symptomatic disease, who had undergone spine surgery, had difficulty with how nusinersen was administered or had not responded to treatment. Parental and patient questionnaires were produced, based on Streiner and Norman's guidelines, 4 to optimise our support.…”

“…It has been very difficult to manage the high expectations that patients and families have had for nusinersen, and this has led to disappointment, frustration and discontinued treatment 3 …”

Ethical aspects of the changing landscape for spinal muscular atrophy management in Australia

“…The long-term effects and outcomes of novel therapies for SMA remain uncertain. 3,14,[24][25][26] While they may prevent further decline, disease-modifying therapies are not a cure for SMA, and children who commence treatment after symptom onset might continue to live with impairment. 27 It is important to manage parental optimism and hope, and ensure that benefits are not overestimated while possible harms are underplayed.…”