Summary of findings for the main comparison. Tafamidis compared to placebo for people with transthyretin‐familial amyloid polyneuropathy (TTR‐FAP).
| Tafamidis compared to placebo for people with transthyretin‐familial amyloid polyneuropathy (TTR‐FAP) | ||||||
| Patient or population: people with early‐stage TTR‐FAP Setting: outpatients Intervention: tafamidis 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 tafamidis | |||||
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Disability due to FAP progression Not measured |
‐ | ‐ | ‐ | ‐ | ‐ | Disability due to FAP progression was not measured |
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Severity of peripheral neuropathy (expressed as the change in NIS‐LL) Scale from: 0 (normal) to 88 (total impairment) Follow‐up: 18 monthsa |
The mean baseline NIS‐LL score in the placebo group was 11.44 points. The mean change from baseline in the placebo group was an increase (worsening) of 5.40 points | The mean change in NIS‐LL score in the tafamidis group was 3.21 points lower (better) than in the placebo group (5.63 points lower to 0.79 points lower) | ‐ | 125 (1 RCT)b | ⊕⊕⊝⊝ Lowc | MCID is 2 NIS‐LL points according to a Peripheral Nerve Society consensus group (Dyck 1997). Tafamidis probably slightly reduces the number of people with progression of peripheral neuropathy compared to placebo. |
| Quality of life (expressed as the change in 35‐Item Norfolk QOL‐DN total score) Scale from: ‐2 (best possible quality of life) to 138 (worst possible quality of life) Follow‐up: 18 monthsa | The mean baseline Norfolk QOL score in the placebo group was 30.80 points. The mean change from baseline in the placebo group was an increase (worsening) of 6.90 points | The mean change in Norfolk QOL score in the tafamidis group was 4.50 points lower (better) than in the placebo group (11.27 points lower to 2.27 points higher) | ‐ | 125 (1 RCT)b | ⊕⊝⊝⊝ Very lowd | MCID was not provided nor reported in the literature. Quality of life may decline slightly less with tafamidis than placebo. |
| Number of participants who died during the trial Follow‐up: 18 monthsa | Study population | RR 0.65 (0.11 to 3.74) | 128 (1 RCT)e | ⊕⊝⊝⊝ Very lowf | It is uncertain whether tafamidis had an effect on the number of participants who died during the trial compared to placebo. | |
| 5 per 100 | 3 per 100 (1 to 18) | |||||
| Number of dropouts due to adverse events Follow‐up: 18 monthsa | Study population | RR 1.29 (0.30 to 5.54) | 128 (1 RCT)e | ⊕⊝⊝⊝ Very lowf | It is uncertain whether tafamidis had an effect on the number of dropouts due to adverse events compared to placebo. | |
| 5 per 100 | 6 per 100 (1 to 26) | |||||
| Number of participants experiencing at least one severe adverse event Follow‐up: 18 monthsa | Study population | RR 1.16 (0.37 to 3.62) | 128 (1 RCT)e | ⊕⊝⊝⊝ Very lowf | It is uncertain whether tafamidis had an effect on the number of participants experiencing at least one severe adverse event compared to placebo. | |
| 8 per 100 | 9 per 100 (3 to 29) | |||||
| *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; NIS‐LL: Neuropathy Impairment Score of the lower limbs; QOL‐DN: Quality of Life‐Diabetic Neuropathy Questionnaire; RCT: randomised clinical trial; 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. bIntention‐to‐treat population. cWe downgraded the certainty of evidence by one level for risk of bias (high risk of attrition bias in the single RCT included in this comparison) and by one level for serious imprecision (CI encompassed a clinically important effect and little or no effect). dWe downgraded the certainty of evidence by one level for risk of bias (high risk of attrition bias in the single RCT included in this comparison), by one level for serious imprecision (CI is wide and includes the possibility of both harms and benefits) and by one level for serious indirectness (mechanisms by which this intervention would affect QOL are not direct). eRandomised population (safety population). fWe downgraded the certainty of evidence by one level for risk of bias (high risk of attrition bias in the single RCT included in this comparison), by two levels for very serious imprecision (small event numbers; and CI includes the possibility of both harms and benefits) and by one level for serious indirectness (events collected by a non‐systematic assessment).