Discussion
OA, pain, viscosupplementation, knee swelling, Reduced pain, joint pain, knee pain
KNEE OSTEOARTHRITIS
The principal finding of this study was that IA PN showed efficacy and safety comparable to IA HMWHA for the treatment of knee OA. Although statistical difference was not significant, the value of VAS (100-mm) change rate for WBP from baseline to 16 weeks was higher in IA PN group (− 54.0 ± 38.1%) than in IA HMWHA group (− 42.8 ± 35.8%). Clinical outcomes of the IA PN groups assessed by using K-WOMAC and EQ-5D were also comparable to that of the IA HMWHA group. All parameters associated with pain VAS and clinical outcomes significantly improved from baseline in both the IA PN and IA HMWHA groups.Previous clinical trials that compared the analgesic efficacy between IA PN and IA HA have shown similar results. Vanelli et alClinical trials comparing clinical efficacy and safety between IA PN and HA in knee osteoarthritis.CurrentStudy(Korea)PN(ConjuranHA(Hyruan PlusHigh MW(3000 kDa)Reduced pain VAS/NSAID use, and improved K-WOMAC / EQ-5D in both group from the baselineNo significant difference in all pain VAS, clinical scores, and rescue drug use between IA PN and IA HMWHA groupsPN: knee pain (n = 3)HA: knee swelling (n = 1) → natual reliefSignificant difference (−)No severe AEs2014(Italy)PN(CondrotideHA(HyalubrixMedium MW(1500–2000 kDa )Reduced pain / NSAID consumption, and KOOS improvement in both groupSignificant KOOS “symptom” improvement(PN : week 2 versus HA : week 18)2013(Romania)PN(CondrotideHA(SynocromMedium MW(1600 kDa )Reduced pain, and improved KOOS and KKS in both group from the baselineSignificantly superior KKS improvement in PN group compare to HA groupMild knee pain(PN: n = 2, HA : n = 1)→ alleviated in a few hoursNo significant AEs2013(Italy)HALow MW2010(Italy)PN(CondrotideHA(SinovialLow MW(800–1200 kDa )Reduced pain VAS/NSAID use, and improved KOOS from the baseline in both groupSimilar trends in pain score between PN and HA groupsPN : mild knee pain (n = 1)→ subsided within onehourIn the present study, IA HMWHA, with a mean MW of 3000 kDa, was used as a control for IA PN, and the results of this study support the use of IA PN as an alternative of IA HMWHA. Despite the well-established clinical efficacy of IA HA, recent OA treatment guidelines report a lack of generalized effects as a limitation of IA HA useAnother interesting finding of this study was that IA PN showed a fast onset of clinical efficacy and a sufficient duration of clinical effect. In this study, pain VAS during weight-bearing, at rest, and walking rapidly reduced within 2 weeks from the baseline and showed a similar pattern in the IA PN and IA HA groups. In Giarrantana et al. studyRegarding AEs related to treatment, minimal local AEs were reported (IA PN: three knee pain, IA HMWHA: one knee swelling) in this study, and local AEs spontaneously relieved without any treatment within a few days. Two systemic and serious AEs in IA PN were found to have no causal relationship with IA injections. The results of this study correspond well with those of previous studies that reported minimal AEs associated with IA PN administration, except for mild joint pain that resolved spontaneously within a few hours (Table Our study had several limitations. First, the number of enrolled centers, patients, and total sample size was relatively small, and therefore, a sufficient number of OA patients with diverse KL grades were not included, and the influence of OA K-L grade on the outcome of intra-articular injection was not evaluated. However, the number of patients in this study was calculated based on statistical power analysis, and there was no significant difference in KL grades between the two groups. Second, in this study, objective imaging assessment was not performed. However, numerous studies on clinical efficacy of intraarticular viscosupplementation such as hyaluronic acid, and polynucleotide mainly investigate pain, and clinical outcomes. It maybe because primary expectation for the use of IA viscosupplementation is pain relief and functional improvement rather structural improvement that can be evaluated with cartilage thickness on MRI or joint space narrowing on plain radiograph. Almost clinical decision to use or stop IAHA or IA PN in outpatient department also performed based on patient’s pain or functional improvement. Therefore, we believe that the results of this study can provide meaningful clinical information related with IA PN use. Third, the maximum follow-up period was 16 weeks from baseline, which was not sufficient for the evaluation of the long-term effects of each treatment. However, both IA PN and HMWHA groups showed a gradual increase in clinical effect until 16 weeks and these two IA viscosupplementations can compensate for the short-acting IA corticosteroids.