Summary of findings 3. Patisiran compared to placebo for people with transthyretin‐familial amyloid polyneuropathy (TTR‐FAP).
| Patisiran compared to placebo for people with transthyretin‐familial amyloid polyneuropathy (TTR‐FAP) | ||||||
| Patient or population: people with TTR‐FAP Setting: outpatient Intervention: patisiran 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 patisiran | |||||
|
Disability due to FAP progression (expressed as the change in R‐ODS) Scale from: 0 (worst disability) to 48 (normal) Follow‐up: 18 monthsa |
The mean baseline R‐ODS score in the placebo group was 29.8 points. The mean change from baseline in the placebo group was a decrease (worsening) of 8.9 points.b |
The mean change in R‐ODS score in the patisiran group was 8.90 points higher (better) than in the placebo group (7.00 points higher to 10.80 points higher).b | ‐ | 225 (1 RCT) | ⊕⊕⊕⊝ Moderatec | MCID not provided nor reported in the literature. Patisiran probably decreases disability due to FAP progression compared to placebo. |
|
Severity of peripheral neuropathy
(expressed as the change in mNIS+7ALN) Scale from: 0 (normal) to 304 (total impairment) Follow‐up: 18 monthsa |
The mean baseline mNIS+7ALN score in the placebo group was 74.6 points. The mean change from baseline in the placebo group was an increase (worsening) of 27.96 points.b |
The mean change in mNIS+7ALN score in the patisiran group was 33.99 points lower (better) than in the placebo group (39.86 points lower to 28.13 points lower).b | ‐ | 225 (1 RCT) | ⊕⊕⊕⊝ Moderatec | MCID not available for this modified NIS+7 scores. Patisiran probably slightly reduces the worsening of peripheral neuropathy compared to placebo. |
|
Quality of life
(expressed as the change in 35‐Item Norfolk QOL‐DN total score) Scale from: ‐4 (best possible quality of life) to 136 (worst possible quality of life) Follow‐up: 18 monthsa |
The mean baseline Norfolk QOL score in the placebo group was 55.5 points. The mean change from baseline in the placebo group was an increase (worsening) of 14.4 pointsb | The mean change in Norfolk QOL score in the patisiran group was 21.10 points lower (better) than in the placebo group (27.20 points lower to 15.00 points lower).b | ‐ | 225 (1 RCT) | ⊕⊕⊝⊝ Lowd | MCID not provided nor reported in the literature. Quality of life may decline slightly less with patisiran than placebo. |
| Number of participants who died during the trial Follow‐up: 18 monthsa | Study population | RR 0.61 (0.21 to 1.74) | 225 (1 RCT) | ⊕⊕⊝⊝ Lowe | There may be no clear difference between the patisiran group and the placebo group in the number of participants who died during the trial. | |
| 8 per 100 | 5 per 100 (2 to 14) | |||||
| Number of dropouts due to adverse events Follow‐up: 18 monthsa | Study population | RR 0.33 (0.13 to 0.82) | 225 (1 RCT) | ⊕⊕⊝⊝ Lowf | There may be little or no difference between the patisiran group and the placebo group in the number of dropouts due to adverse events. | |
| 13 per 100 | 5 per 100 (2 to 12) | |||||
| Number of participants experiencing at least one severe adverse event Follow‐up: 18 monthsa | Study population | RR 0.91 (0.64 to 1.28) | 225 (1 RCT) | ⊕⊕⊝⊝ Lowe | There may be little or no difference between the patisiran group and the placebo group in the number of participants with at least one severe adverse event. | |
| 40 per 100 | 37 per 100 (26 to 52) | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval;FAP: familial amyloid polyneuropathy;MCID: minimum clinically important difference; mNIS+7ALN: modified Neuropathy Impairment Score plus 7 nerves test (Alnylam);QOL‐DN: Quality of Life‐Diabetic Neuropathy Questionnaire; RCT: randomised clinical trial;ROD‐S: Rasch‐built Overall Disability Scale; RR: risk ratio; TTR: transthyretin. | ||||||
| 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. | ||||||
aEnd of the study. bMeans change from baseline and mean differences between groups refer to least‐squares means and least‐squares mean differences, respectively. cWe downgraded the certainty of evidence by one level for serious imprecision. dWe downgraded the certainty of evidence by one level for serious imprecision and by one level for serious indirectness (mechanisms by which this intervention would affect QOL are not direct). eWe downgraded the certainty of evidence by two levels for very serious imprecision (small event numbers and CI includes the possibility of both harms and benefits). fWe downgraded the certainty of evidence by two levels for very serious imprecision (small event numbers and wide CI).