Table 3.
Summary of safety findings for intra-articular hyaluronic acid (IAHA) compared to placebo in patients with osteoarthritisOrgan Class, TRAEs treatment-related adverse events
| Outcomes | No. of participants (studies), follow-up | Certainty of the evidence (GRADE) | Overall relative effect (95% CI) | Anticipated absolute effects | |
|---|---|---|---|---|---|
| Risk with placebo | Risk difference with IAHA | ||||
| Gastrointestinal adverse events | 1936 (11 RCTs) | ⊕⊕⊕◯ MODERATE |
0.81 (0.52–1.27) | 87 per 1000 | 15 fewer per 1000 (40 fewer to 21 more) |
| Cardiac disorders | 2560 (13 RCTs) | ⊕⊕◯◯ LOWa,b |
1.25 (0.36–4.41) | 3 per 1000 | 1 more per 1000 (2 fewer to 11 more) |
| Vascular disorders | 2560 (13 RCTs) | ⊕⊕◯◯ LOWa,b |
1.70 (0.39–7.29) | 2 per 1000 | 2 more per 1000 (1 fewer to 15 more) |
| Respiratory, thoracic and mediastinal disorders | 2560 (13 RCTs) | ⊕⊕⊕◯ MODERATEa |
1.21 (0.82–1.78) | 42 per 1000 | 8 more per 1000 (7 fewer to 30 more) |
| Nervous system disorders | 2089 (11 RCTs) | ⊕⊕⊕◯ MODERATEa |
1.15 (0.77–1.70) | 54 per 1000 | 8 more per 1000 (12 fewer to 35 more) |
| Skin and subcutaneous tissue disorders | 1173 (8 RCTs) | ⊕⊕◯◯ LOWa,b |
1.71 (0.52–5.63) | 18 per 1000 | 12 more per 1000 (8 fewer to 74 more) |
| Musculoskeletal and connective tissue disorders | 2962 (13 RCTs) | ⊕⊕⊕◯ MODERATEa |
0.99 (0.71–1.39) | 101 per 1000 | 1 fewer per 1000 (27 fewer to 34 more) |
| Renal and urinary disorders | 2560 (13 RCTs) | ⊕⊕⊕◯ MODERATEa |
0.54 (0.21–1.41) | 10 per 1000 | 4 fewer per 1000 (8 fewer to 4 more) |
| Infections and infestations | 2019 (11 RCTs) | ⊕⊕⊕◯ MODERATEa |
0.61 (0.40–0.93) | 65 per 1000 | 24 fewer per 1000 (38 fewer to 4 fewer) |
| Hypersensitivity reaction | 2560 (13 RCTs) | ⊕⊕◯◯ LOWa,b |
0.64 (0.05–7.94) | 15 per 1000 | 5 fewer per 1000 (14 fewer to 94 more) |
| Severe adverse events | 3232 (14 RCTs) | ⊕⊕⊕◯ MODERATEa |
1.08 (0.50–2.31) | 16 per 1000 | 1 more per 1000 (8 fewer to 20 more) |
| Serious adverse events | 3956 (16 RCTs) | ⊕⊕⊕◯ MODERATEa |
1.78 (1.21–2.63) | 22 per 1000 | 17 more per 1000 (5 more to 34 more) |
| Withdrawals due to adverse events | 3540 (15 RCTs) | ⊕⊕⊕◯ MODERATEa |
1.62 (1.04–2.51) | 26 per 1000 | 15 more per 1000 (1 more to 36 more) |
| Any adverse event | 3476 (14 RCTs) | ⊕⊕⊕◯ MODERATEa |
1.09 (0.90–1.31) | 487 per 1000 | 22 more per 1000 (26 fewer to 67 more) |
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
The risk in the intervention group and its 95% CI are based on the assumed risk in the comparison group and the relative effect of the intervention and its 95% CI
CI confidence interval, OR odds ratio, RCT randomized controlled trial
aHigh risk of incomplete outcome data (attrition bias) and selective outcome reporting (reporting bias) found in many of the included studies. Full safety data were provided by authors of manuscripts for only 2 studies
bWide CI because of low number of events