Table 4

Adverse events

StudySample sizeSeverityProduct (HA)Control (Sa, IAS)Number of injectionsDurationAEs
Altman et al17346K-L II-IVNASHA (Durolane)Saline (Sa)126 weeksTreatment-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 al18588K-L II-IIIBioHASaline (Sa)326 weeksTreatment-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 al19216Not reportedHylan G-F 20 (Synvisc)Triamcinolone hexacetonide (IAS)3, 126 weeksNo 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 al20253K-L II-IIIHylan G-F 20 (Synvisc)Saline (Sa)126 weeksNo 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
Day21240Mild to Moderate; <K-L IV25 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 Da2.5 mL of the Buffered saline (Sa) (batch no. C4F28S)518 weeksTreatment-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 al2230K-L II-IIIHA 20 mg/mLHA 0.001 mg/mL36 monthsNo significant AEs reported; limited number of patients reported minor discomfort during the injection process
Housman22391K-L II-IIIHylastan 2, 1Methylprednisone acetate (IAS)2, 126 weeksFrequencies 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 al27200K-L II-IIIHyalganSaline (Sa)526 weeksMore 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 al24442K-L II-IIINASHA (Durolane)Methylprednisone acetate (IAS)112 weeksDuring 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 al25306K-L II-III1% Sodium hyaluronateSaline (Sa)540 monthsOverall frequency of at least one adverse event=83%, same in both treatment groups (n=11 in each); no serious AEs reported
Strand et al26379K-L I-IIIGel-200Saline (Sa)113 weeksIncidence 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.