Study | Comparison | Follow-up | Outcomes | Effect estimate | Comments |
Knee osteoarthritis | |||||
Bannuru et al4 | HA vs PBO | 4–52 weeks | Any AEs | No between group differences (vs PBO) | NMA specifically aimed at analysing safety. Comparisons are between PBO and all RCTs of individual HA products. No pooled analysis of HA as a group was carried on. |
Local reactions | Analyses favoured PBO for 2/17 products assessed | ||||
Withdrawal due to AEs | Analyses favoured PBO for 1/11 products assessed | ||||
Bannuru et al5 | HA vs PBO HA vs IAGC IAGC vs PBO | 2–6 months | Any AE | HA vs PBO: 16 (54.6) vs 21.7 (56.0) | No pooled analysis was carried on. Results are median (IQR) of event rates, % |
HA vs IAGC: 0.0 (64.6) vs 5.5 (57.2) | |||||
IAGC vs PBO: No data | |||||
SAEs | HA vs PBO: 0 (0.9) vs 0 (0) | ||||
HA vs IAGC: 0.0 (2.0) vs 0.0 (4.3) | |||||
IAGC vs PBO: No data | |||||
Withdrawal due to AEs | HA vs PBO: 0.9 (3.9) vs 1.0 (2.6) | ||||
HA vs IAGC: 1.9 (3.7) vs 2.7 (6.0) | |||||
IAGC vs PBO: 0.0 (3.5) vs 0.0 (1.7) | |||||
Local reactions | HA vs PBO: 8.4 (14.4) vs 4.7 (16.1) | ||||
HA vs IAGC: 2.2 (21.8) vs 3.0 (9.1) | |||||
IAGC vs PBO: 3.3 (17.9) vs 6.9 (8.0) | |||||
Septic joint | HA vs PBO: 0 (0) vs 0 (0) | ||||
HA vs IAGC: 0 (0) vs 0 (0) | |||||
IAGC vs PBO: 0 (0) vs 0 (0) | |||||
Newberry et al22 | HA vs PBO | 1–12 months | Local reactions | OR 0.70 (0.48 to 1.03). No between-group difference | |
Joint pain | OR 0.83 (0.60 to 1.15). No between-group difference | ||||
Serious join reactions | OR 0.77 (0.25 to 2.31). No between-group difference | ||||
Other AE | OR 1.26 (0.94 to 1.68). No between-group difference | ||||
Other SAE | OR 0.62 (0.23 to 1.57). No between-group difference | ||||
Trojian et al30 | HA vs PBO | 2–6 months | Joint pain | 1 RCT—HA vs IAGC —17% vs 3.2%, p<0.05 | Some RCTs did not report data on withdrawal due to AE |
IAGC vs PBO | 10 RCT—no between-group difference | ||||
HA vs IAGC | Any AE | 11 RCTs—no between-group difference | |||
SAEs | 11 RCTs—no between-group differences | ||||
Withdrawal due to AEs | 4 RCTs—no between-group differences | ||||
Rutjes et al7 | HA vs sham or no intervention | 3 months | Local reactions | RR=1.34 (1.13 to 1.60) | †RR for SAE resulted from pooling 14 RCTs. ¥RR for withdrawals resulted from pooling 23 RCTs. The effect was not maintained when pooling large unblinded RCTs. |
Any AE | RR=1.04 (0.99 to 1.09). No between-group differences | ||||
SAEs† | Overall, RR=1.41 (1.02 to 1.97) | ||||
Large blinded RCTs, RR=1.55 (1.07 to 2.24) | |||||
Withdrawal due to AEs¥ | RR=1.33 (1.01 to 1.74) | ||||
Jüni et al23 | IAGC vs sham or no intervention | 2 weeks to 6 months | Any AE | RR=0.89 (0.64 to 1.23) | |
SAEs | RR=0.63 (0.15 to 2.67) | ||||
Withdrawal due to AEs¥ | RR=0.33 (0.05 to 2.07) | ||||
Brazilian Medical Association34 | MPA vs TA or TH or BP | 4–24 weeks | Any AE | 1 RCT—o AE reported | |
1 RCT—no data on AE | |||||
1 RCT—no between-group differences | |||||
Shen et al29 | PRP vs HA or IAGC or PBO | 3–12 months | Any AE | RR=1.40 (0.80 to 2.45). | Comparisons were mainly with HA |
SAE | No SAEs were identified | ||||
Kanchanatawan et al25 | PRP vs HA or PBO | 6–12 months | Any AE | RR=0.85 (0.57 to 1.28) (vs HA) | |
RR=6.30 (0.34 to 117.48) (vs PBO) | |||||
SAEs | No data reported | ||||
Dai et al27 | PRP vs HA or PBO | 6–12 months | Any AE | RR=0.63 (0.20 to 1.98) (vs HA) | |
RR=2.63 (0.04 to 158.93) (vs PBO) | |||||
SAEs | No data reported | ||||
Di et al32 | PRP vs HA | 1–12 months | Any AE | 1 RCT—significantly more pain in PRP group | |
1 RCT—reported no AEs | |||||
1 RCT—o safety data reported | |||||
4 RCT—no between-group differences | |||||
SAE | 5 RCT—reported no SAEs | ||||
Ding et al24 | MSC vs PBO or HA or IAGC | 6–12 months | Any AE | No data reported | |
SAE | OR=1.95 (0.89 to 4.26) | ||||
Hip osteoarthritis | |||||
Leite et al40 | HA vs PBO or MPA | 1–12 months | Any AE | RR=1.07 (0.78 to 1.48) (vs PBO) | |
RR=2.24 (0.24 to 20.85) (vs MPA) | |||||
3 RCTs—no between-group differences. (vs PBO) | |||||
Liao et al37 | HA vs PBO | 2 weeks to 6 months | Any AE | 4 RCTs—no between-group differences | |
SAE | 1 RCT—one septic arthritis episode on the HA group | ||||
Withdrawal due to AEs | 1 RCT—no between-group differences | ||||
McCabe et al38 | IAGC vs PBO | 1–3 months | Any AE | 2 RCTs—none reported | |
2 RCTs—no between-group differences | |||||
Medina-Porqueres et al41 | PRP vs HA | 1–12 months | Any AE | 1 RCT—more pain in PRP group (p<0.05) | |
1 RCT—reported one sup haematoma on PRP group | |||||
Ye et al42 | PRP vs HA | 2–12 months | Any AE | RR=0.95 (0.40 to 2.24) | |
Shoulder capsulitis | |||||
Lee et al44 | HA vs PBO | 3–6 months | Any AE | 2 RCTs—no AE reported | |
2 RCTs—no data on AE | |||||
Buchbinder et al43 | TA 40 mg vs TA 10 mg | 4–6 weeks | Any AE | No between-group differences | |
Sun et al45 | IAGC vs PBO | 4–26 weeks | Any AE | 3 RCTs—no between-group differences | |
5 RCTs—no data on AE | |||||
Rheumatoid arthritis | |||||
Saito and Kotake47 | HA vs PBO | 1 week | Any AE | RR=0.98 (0.94 to 1.02) | |
Silvinato and Bernardo34 | MPA vs TH or TA | 1–6 months | Any AE | 1 RCT—no AE reported | |
1 RCT—no data on AE |
All effect sizes are presented as the point estimate (95% CI) unless otherwise stated.
AE, adverse events; HA, hyaluronic acid; IAGC, intra-articular glucocorticoids; MPA, methylprednisolone acetate; MSC, mesenchymal stem cells; NMA, Network Meta-analysis; PBO, placebo; PRP, platelet-rich plasma; RCT, randomised controlledl trials; RR, relative risk; SAE, serious adverse events; TA, triamcinolone acetonide; TH, triamcinolone hexacetonide.