Table 3.
GRADE evidence profile.
| Certainty assessment |
Summary of findings |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Participants (studies) follow-up | Risk of bias | Inconsistency | Indirectness | Imprecision | Publication bias | Overall certainty of evidence | Study event rates (%) |
Relative effect (95% CI) | Anticipated absolute effects |
||
| With [placebo] | With [difelikefalin] | Risk with [placebo] | Risk difference with [difelikefalin] | ||||||||
| Mean change from baseline in the weekly NRS score (week 4) | |||||||||||
| 752 (4 RCTs) | Not serious | Not serious | Not serious | Not serious | None | ⊕⊕⊕⊕High | 381 | 371 | – | – | MD 0.98 lower (1.28 lower to 0.68 lower) |
| Mean change from baseline in the weekly NRS score (week 8) | |||||||||||
| 578 (3 RCTs) | Not serious | Not serious | Not serious | Not serious | None | ⊕⊕⊕⊕ High | 292 | 286 | – | – | MD 1 lower (1.39 lower to 0.61 lower) |
| Mean change from baseline in 5-D itch scale total score | |||||||||||
| 749 (4 RCTs) | Not serious | Seriousa | Not serious | Seriousb | None | ⊕⊕◯◯ Low | 379 | 370 | – | – | MD 1.51 lower (2.26 lower to 0.76 lower) |
| Mean change from baseline in Skindex-10 scale total score | |||||||||||
| 467 (2 RCTs) | Not serious | Seriousa | Not serious | Seriousb | None | ⊕⊕◯◯ Low | 234 | 233 | – | – | MD 7.39 lower (12.51 lower to 2.28 lower) |
| ≥3 point improvement from baseline in weekly mean NRS score | |||||||||||
| 602 (3 RCTs) | Not serious | Seriousa | Not serious | Very seriousb | None | ⊕◯◯◯ Very low | 90/309 (29.1%) | 139/293 (47.4%) | RR 1.61 (1.13 to 2.31) | 291 per 1000 | 178 more per 1000 (from 38 more to 382 more) |
| ≥4 point improvement from baseline in weekly mean NRS score | |||||||||||
| 602 (3 RCTs) | Not serious | Seriousa | Not Serious | Very seriousb | None | ⊕◯◯◯ Very low | 60/309 (19.4%) | 109/293 (37.2%) | RR 1.94 (1.21 to 3.11) | 194 per 1000 | 183 more per 1000 (from 41 more to 410 more) |
| Patient global impression of change (PGIC) | |||||||||||
| 381 (3 RCTs) | Not serious | Not serious | Not serious | Seriousc | None | ⊕⊕⊕◯ Moderate | 62/193 (32.1%) | 108/188 (57.4%) | RR 1.79 (1.42 to 2.27) | 321 per 1000 | 254 more per 1000 (from 135 more to 408 more) |
| Adverse events - any adverse events | |||||||||||
| 768 (4 RCTs) | Not serious | Seriousa | Not serious | Seriousb | None | ⊕⊕◯◯ Low | 220/385 (57.1%) | 264/383 (68.9%) | RR 1.26 (1.03 to 1.55) | 571 per 1000 | 149 more per 1000 (from 17 more to 314 more) |
| Adverse events - any serious adverse events | |||||||||||
| 768 (4 RCTs) | Not serious | Not serious | Not serious | Very seriousb | None | ⊕⊕◯◯ Low | 57/385 (14.8%) | 74/383 (19.3%) | RR 1.42 (0.78 to 2.57) | 148 per 1000 | 62 more per 1000 (from 33 fewer to 232 more) |
| Adverse events - adverse events leading to discontinuation | |||||||||||
| 768 (4 RCTs) | Not serious | Not serious | Not serious | Very seriousb | None | ⊕⊕◯◯ Low | 15/385 (3.9%) | 28/383 (7.3%) | RR 1.80 (0.97 to 3.35) | 39 per 1000 | 31 more per 1000 (from 1 fewer to 92 more) |
| Adverse events - death | |||||||||||
| 768 (4 RCTs) | Not serious | Not serious | Not serious | Very seriousb | none | ⊕⊕◯◯ Low | 4/385 (1.0%) | 3/383 (0.8%) | RR 0.81 (0.19 to 3.34) | 10 per 1000 | 2 fewer per 1000 (from 8 fewer to 24 more) |
Note: CI: confidence interval; MD: mean difference; RR: risk ratio. Boldface is used to highlight the most important or statistically significant results/findings.
aI-square >50%.
bWide conference interval & the number of events is less than 300 events.
cThe number of events is less than 300 events.