Adverse events
| Study | Sample size | Severity | Product (HA) | Control (Sa, IAS) | Number of injections | Duration | AEs |
|---|---|---|---|---|---|---|---|
| Altman et al17 | 346 | K-L II-IV | NASHA (Durolane) | Saline (Sa) | 1 | 26 weeks | Treatment-related AEs: HA=12.8% vs S=8.0%; arthralgia: HA=6.4% vs Sa=2.9%; >70% of treatment-related AEs reported within 2 days in both treatment groups; 9 treatment-related AEs led to withdrawal (HA=5, Sa=4), 1 worsening knee OA pain (HA), 1 knee synovitis (S); no serious treatment-related AEs |
| Altman et al18 | 588 | K-L II-III | BioHA | Saline (Sa) | 3 | 26 weeks | Treatment-related AEs: HA=10% vs S=11%; arthralgia: HA=9% vs Sa=12%; 8 treatment-related AEs led to withdrawal (HA=3, Sa=5); no joint effusions in treatment group |
| Caborn et al19 | 216 | Not reported | Hylan G-F 20 (Synvisc) | Triamcinolone hexacetonide (IAS) | 3, 1 | 26 weeks | No statistically significant differences observed between treatment groups for overall incidence of adverse events or IAS incidence of any single adverse event; majority of adverse events reported were not considered to be related to the study treatments; number and severity of local injection-site reactions comparable between treatment groups; injection site-related events HA=7% vs IAS=10% (p=0.224); swelling related events HA=8% vs IAS=12% (p=0.136); discontinuation due to adverse events HA=10% vs IAS=10%; 9 serious adverse events in 6 patient in IAS group considered not to be treatment related |
| Chevalier et al20 | 253 | K-L II-III | Hylan G-F 20 (Synvisc) | Saline (Sa) | 1 | 26 weeks | No target knee serious AEs; no treatment related serious AEs; incidence of AEs HA=5.7% vs Sa=3.1% (p=0.366); no difference in treatment-related AEs (p=0.203) or procedure-related target knee AEs (p=0.531), all of which HA were mild or moderate |
| Day21 | 240 | Mild to Moderate; <K-L IV | 25 mg of sodium HA in 2.5 mL of phosphate buffered saline (ARTZTM; batch no. C4F27S). The sodium HA was extracted from rooster combs and the purified material has a molecular weight of 6.2 to 11.7×105 Da | 2.5 mL of the Buffered saline (Sa) (batch no. C4F28S) | 5 | 18 weeks | Treatment-related adverse events type and incidence between the active and control groups was similar. The most frequent adverse event was injection site pain (HA group 16; controls 13); dropout was 4% HA and 6% control |
| DeCaria et al22 | 30 | K-L II-III | HA 20 mg/mL | HA 0.001 mg/mL | 3 | 6 months | No significant AEs reported; limited number of patients reported minor discomfort during the injection process |
| Housman22 | 391 | K-L II-III | Hylastan 2, 1 | Methylprednisone acetate (IAS) | 2, 1 | 26 weeks | Frequencies of overall AEs and target knee AEs comparable between groups; most frequent target knee AEs in all 3 groups: arthralgia, stiffness, swelling, effusion with no differences between groups; majority mild or moderate; no significant changes in vital signs, antibody testing results or lab safety concerns |
| Huang et al27 | 200 | K-L II-III | Hyalgan | Saline (Sa) | 5 | 26 weeks | More patients in the placebo group experienced at least 1 AE (48% vs 39%), all mild-moderate, none considered related to study treatment; 5 serious AEs reported HA=3 vs S=2, all considered unrelated to study treatment; statistically significant change from baseline in platelet counts between groups at 5 weeks not felt to be clinically significant (p=0.027) |
| Leighton et al24 | 442 | K-L II-III | NASHA (Durolane) | Methylprednisone acetate (IAS) | 1 | 12 weeks | During the blinded phase treatment-related AEs: HA=64 vs IAS=15 (no p value reported); Arthralgia was the largest component 38 (17.2%) vs 7 (3.2%) (p<0.01) with most TRAE reported within 3 days of injection and resolved within 2–3 weeks ; no treatment-related serious AEs; during open-labeled extension, no allergic reactions to the 2nd injections observed |
| Navarro-Sarabia et al25 | 306 | K-L II-III | 1% Sodium hyaluronate | Saline (Sa) | 5 | 40 months | Overall frequency of at least one adverse event=83%, same in both treatment groups (n=11 in each); no serious AEs reported |
| Strand et al26 | 379 | K-L I-III | Gel-200 | Saline (Sa) | 1 | 13 weeks | Incidence of AEs similar in both treatment groups; 182 treatment-related AEs reported in 100 patients: HA=26.9% vs S=25.8%; joint swelling, effusion, arthralgia most common and not significantly different between groups; no clinically notable lab result changes |
AE, adverse events; HA, hyaluronic acid; IAS, intra-articular corticosteroids; OA, osteoarthritis; TRAE, treatment-related adverse events.