Healthcare utilisation in children with SMA type 1 treated with nusinersen: a single centre retrospective review

Abstract

BackgroundNusinersen has been used to treat spinal muscular atrophy type 1 (SMA1) in the UK since 2017. While initial trials showed neuromuscular benefit from treating SMA1, there is little information on the respiratory effects of nusinersen. We aimed to look at the respiratory care, hospital utilisation and associated costs in newly treated SMA1.MethodsWe reviewed the medical records of all children within the West Midlands with SMA1 treated with nusinersen at Royal Stoke University Hospital. Baseline demographics and hospital admission data were collected including: the reason for admission, total hospital days, days of critical care, days intubated, discharge diagnosis, doses of nusinersen and treatment complications.Results11 children (six girls) received nusinersen between May 2017 and April 2019. Their median (range) age was 29 (7–97) months. The median (range) number of nusinersen doses per child was 6 (4–8). All children were receiving long-term ventilatory support; this was mask ventilation in nine and tracheostomy ventilation in two. The total number of hospital days since diagnosis was 1101 with a median (range) of 118 (7–235) days per child. This included general paediatric ward days 0 (0–63), High Dependency Unit 79 (7–173) days and Paediatric Intensive Care Unit 13 (0–109) days per child. This equated to a median (range) of 20 (2–72) % of their life in hospital. The estimated cost of this care was £2.2M.ConclusionPatients with SMA1 treated with nusinersen initially spend a considerable proportion of their early life in hospital. Parents should be counselled accordingly. These data suggest that for every 10 children started on nusinersen an extra HDU bed is required. This has a significant cost implication.

Systematic Literature Review to Assess the Cost and Resource Use Associated with Spinal Muscular Atrophy Management

“…The publications comprised data from 14 countries, including the USA (n = 20) [48-50, 53, 54, 56, 57, 60, 63, 70, 74, 77, 80, 84-86, 88, 91-93], UK (n = 5) [52,68,81,89,98], Italy (n = 2) [59,83], Australia (n = 2) [64,71], Canada (n = 1) [75], Germany (n = 1) [55], Croatia (n = 1) [87], Korea (n = 1) [65], Japan (n = 1) [66], France (n = 1) [79], Spain (n = 4) [58,72,73,78], Sweden (n = 1) [61], Russia (n = 2) [94,97] and Turkey (n = 1) [96]. Seven studies reported multi-national data [62,67,69,76,82,90,95].…”

“…b Covering 49 unique studies; two full publications and two conference abstracts were linked studies; both have been retained in the current report as they each report unique relevant data. EBM evidence-based medicine reviews, SLR systematic literature review frequently reported separately for individuals with Type 1 (n = 11) [48,54,57,63,65,66,68,81,84,91,93]; Types 1-3 SMA (n = 11; each type reported separately [52,55,58,59,67,69,71,75,76,96,98]; Type 3 SMA including subgroups (n = 1) [82]; and adult patients with SMA (n = 1) [74] or were reported for a mixed population of individuals with SMA: infantile-onset and other SMA (excluding Type 4 SMA; n = 1) [79]; infantile-onset (≤ 7 years) and later-onset (2-12 years) SMA (n = 1) [61]; Type 1 SMA and other SMA (including Type 4 SMA; n = 2) [50,97]; early-onset SMA (patients with Types 1, 2 and 3 SMA aged ≤ 3 years); and other SMA (later-onset Types 2 and 3 SMA in addition to Type 4 SMA) [n = 1] [60]-reported separately for infantile-onset, childhood-onset and juvenile-onset SMA (n = 1) [70]; reported separately for patients with infantile-onset, childhood-onset and late-onset SMA (n = 1) [77]; a mixed population with Types 1, 2 and 3 SMA (n = 1) [95]; a mixed population with Types 2 and 3 SMA (n = 1) [64]; a mixed population with Types 2 and 3 SMA including subgroups (n = 1) [62]; a mixed population with Types 2 and 3 and unreported SMA type (n = 1) [88]; a mixed population with Types 1, 2, 3 and 4 SMA (n = 1) [73]; and a mixed population with SMA in whi...…”

“…Of the 51 publications included in the SLR, 12 included data that examined the use of DMTs nusinersen and onasemnogene abeparvovec; four were full-text publications [50,61,63,68], whereas eight were abstracts [48,49,51,81,88,90,91,93]. Because of earlier approval in the USA and Europe for nusinersen, most of the 12 publications examined nusinersen only [50,51,61,68,81,88,90,93], whereas three publications compared treatment with onasemnogene abeparvovec vs nusinersen [48,49,63], and one publication examined onasemnogene abeparvovec [91]. No data are currently available for the effect of treatment with risdiplam on cost and resource use as a result of the recent approval of risdiplam in the USA and Europe.…”

“…However, a sensitivity analysis to test the robustness of findings was rarely conducted. Limitations of individual studies included: (1) small sample sizes because of the rarity of the disease (n = 11) [50, 58-60, 62, 64, 65, 68, 69, 76, 77]; (2) potential biases and inability to adjust for confounding factors in retrospective and cross-sectional study designs (n = 5) [55,58,65,68,76]; (3) potential underestimation of costs due to consideration of indirect costs only or restriction of costs to a particular setting, such as a hospital (n = 7) [50,53,54,59,68,74,77]; (4) inherent limitations of claims databases including the potential for coding errors and other inaccuracies (n = 9) [50,53,56,60,70,72,73,77,78]; (5) limited generalisability of results beyond study settings, i.e. to different countries and healthcare systems (n = 5) [50,53,64,70,77], ( 6) reliance of self-reported data, which may lead to potential recall or response bias (n = 4) [52,58,69,75]; (7) potential selection bias due to recruitment of patients via advocacy groups or organisations (n = 4) [52,55,58,76]; and (8) estimates calculated before approval of nusinersen; therefore, estimates may not be reflective of patients treated with this DMT (n = 1) [54].…”

SMN-deficiency disrupts SERCA2 expression and intracellular Ca2+ signaling in cardiomyocytes from SMA mice and patient-derived iPSCs

“…SMA patients with more than two copies of SMN2, as a result of duplication, tend to have less severe forms of the disease. Recently, therapeutic breakthroughs, genereplacement therapy using viral delivery [3] and altering SMN2 splicing using antisense oligonucleotides [4], have remarkably improved motor function and survival of SMA patients, but patients remain prone to cardiopulmonary complications leading to opportunistic upper respiratory tract infections [5].…”