Summary of findings 7. Subcutaneous somatotropin compared to placebo for children and adults with SMA types II and III.
| Subcutaneous somatotropin compared to placebo for children and adults with SMA types II and III | |||||||
| Patient or population: children and adults with SMA types II and III Setting: outpatient clinic Intervention: subcutaneous somatotropin Comparison: placebo | |||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | ||
| Risk with placebo | Risk with subcutaneous somatotropin | ||||||
| Change in disability score assessed with: HFMSE Scale: 0–66 Follow‐up: 3 months | The median change in disability score was –1.05 | Median change 0.25 higher (1 lower to 2.5 higher) | — | 19 (1 cross‐over RCT) | ⊕⊝⊝⊝ Very lowa,b | Higher scores on the HFMSE indicate better function. | |
| Change in muscle strength assessed with: MMT with hand‐held myometry from Citec (in Newtons) Follow‐up: 3 months | Upper limbs | The mean change in muscle strength (upper limbs) was 0.30 N | MD 0.08 N lower (3.79 lower to 3.95 higher) | — | 19 (1 cross‐over RCT) | ⊕⊕⊝⊝ Lowb,c | — |
| Lower limbs | The mean change in muscle strength (lower limbs) was 0.95 N | MD 2.23 N higher (2.19 lower to 6.63 higher) | — | 19 (1 cross‐over RCT) | ⊕⊕⊝⊝ Lowb,c | — | |
| Acquiring the ability to stand or walk | Not measured | ||||||
|
Change in quality of life Follow‐up: 40 weeks |
The trial report states that the trial found no significant differences in quality of life between the somatotropin‐treated group and the placebo group. | — | 19 (1 cross‐over RCT) | ⊕⊝⊝⊝ Very lowb,d | |||
| Change in pulmonary function assessed with: FVC (in litres) Follow‐up: 3 months | The mean change in pulmonary function was –0.11 L | MD 0.22 L higher (0.02 lower to 0.4 higher) | — | 19 (1 cross‐over RCT) | ⊕⊕⊝⊝ Lowb,c | — | |
| Time from beginning of treatment until death or full‐time ventilation Follow‐up: mean 40 weeks | No participant died or required full‐time ventilation in either group | — | 19 (1 cross‐over RCT) | ⊕⊕⊝⊝ Lowb,c | — | ||
| Adverse events related to treatment Follow‐up: 40 weeks | 368 per 1000 | 578 per 1000 (278 to 1000) | RR 1.57 (0.78 to 3.17) | 19 (1 cross‐over RCT) | ⊕⊕⊝⊝ Lowc,e | 23 adverse events occurred, 14 during somatotropin treatment and 9 during placebo treatment. Adverse events were systematically, prospectively collected at every study visit. Adverse events included headache, arthralgia, myalgia, oedema, elevated serum thyroid‐stimulating hormone and myalgia. | |
| *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; FVC: forced vital capacity; HFMSE: Hammersmith Functional Motor Score Expanded; MD: mean difference; MFM: Motor Function Measure; MMT: Manual Muscle Testing; RCT: randomised controlled trial; RR: risk ratio; SMA: spinal muscular atrophy. | |||||||
| 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 two levels due to risk of bias. HFMSE ranges were not available and because of the potential carry‐over effect due to the cross‐over design. b Downgraded one level for imprecision because of very small study size. c Downgraded one level because of potential bias from carry‐over effects due to the cross‐over design. d Downgraded two levels due to risk of bias. The report provided no information about how quality of life was measured and did not provide numerical data. There was a potential carry‐over effect due to the cross‐over design. e Downgraded for imprecision because the small sample size is unlikely to have captured uncommon adverse events.