Summary of findings 4. Intrathecal injected nusinersen compared to sham procedure for children with SMA type II.
| Intrathecal injected nusinersen compared to sham procedure for children with SMA type II | |||||||
| Patient or population: children with SMA type II Setting: hospital visits (24 hours' observation at trial site after first procedure, 6 hours' observation after subsequent injections) Intervention: intrathecal injected nusinersen Comparison: sham procedure | |||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | ||
| Risk with sham procedure | Risk with intrathecal injected nusinersen | ||||||
| Change in disability score assessed with: HFMSE Score: 0–66 Follow‐up: mean 15 months | The mean change in HFMSE in the control group was –1.9 points | The mean change in HFMSE in the nusinersen‐treated group was 5.9 points higher than in the sham procedure group (3.7 higher to 8.1 higher) | MD 5.9 (3.7 to 8.1) | 126 (1 RCT) | ⊕⊕⊕⊝ Moderatea | ||
| Change in disability score (3 point‐change) assessed with: HFMSE Follow‐up: mean 15 months | 262 per 1000 | 471 per 1000 (259 to 812) |
RR 1.8 (0.99 to 3.1) |
126 (1 RCT) | ⊕⊕⊕⊝ Moderatea | 11/42 participants in the sham‐controlled group showed a 3‐point change on the HFMSE. 48/84 participants in the nusinersen group showed a 3‐point change on the HFMSE. | |
| Change in muscle strength | Not measured | ||||||
| Acquiring the ability to stand or walk assessed with: WHO Motor Milestone criteria Follow‐up: 15 months | Acquiring the ability to stand | 1/42 children in the sham‐controlled group acquired the ability to stand alone. | 1/84 children treated with nusinersen acquired the ability to stand alone. | RR 0.5 (0.03 to 7.80) | 126 (1 RCT) | ⊕⊕⊝⊝ Lowb | |
| Acquiring the ability to walk | 0/42 children in the sham‐controlled group acquired the ability to walk with assistance. | 1/84 children treated with nusinersen acquired the ability to walk with assistance. | RR 1.5 (0.06 to 36.1) | 126 (1 RCT) | ⊕⊕⊝⊝ Lowb | ||
| Change in quality of life | Not measured | ||||||
| Change in pulmonary function | Not measured | ||||||
| Time from beginning of treatment until death or full‐time ventilation | Not measured | ||||||
| Adverse events related to treatment Follow‐up: mean 15 months | 1000 per 1000 | 900 per 1000 | RR 0.9 (0.9 to 1.0) | 126 (1 RCT) | ⊕⊕⊕⊝ Moderatec | 78/84 (93%) participants treated with nusinersen experienced an adverse event, while 42/42 (100%) participants treated in the sham‐controlled group had any adverse event. Adverse events were systematically, prospectively collected at every study visit. Adverse events included proteinuria, hyponatraemia, transient low platelet counts, vasculitis, pyrexia, headache, vomiting, back pain and epistaxis. |
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| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; HFMSE: Hammersmith Functional Motor Measure Expanded; MD: mean difference; MHFMS: Modified Hammersmith Functional Motor Scale; MMT: manual muscle testing; RCT: randomised controlled trial; RR: risk ratio; SMA: spinal muscular atrophy; WHO: World Health Organization. | |||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | |||||||
a Downgraded one level for imprecision because of the small sample size. b Downgraded two levels for imprecision because of small sample size, low event rate and wide CI. c Downgraded one level for imprecision because the small sample size is unlikely to have captured uncommon adverse events.