title: Hyaluronic Acid Injections Are Associated with Delay of Total Knee Replacement Surgery in Patients with Knee Osteoarthritis: Evidence from a Large U.S. Health Claims Database.
abstract: BACKGROUND
  The growing prevalence of osteoarthritis (OA) and the medical costs associated with total knee replacement (TKR) surgery for end-stage OA motivate a search for agents that can delay OA progression. We test a hypothesis that hyaluronic acid (HA) injection is associated with delay of TKR in a dose-dependent manner.
  
  
  RESULTS
  We retrospectively evaluated records in an administrative claims database of ~79 million patients, to identify all patients with knee OA who received TKR during a 6-year period. Only patients with continuous plan enrollment from diagnosis until TKR were included, so that complete medical records were available. OA diagnosis was the index event and we evaluated time-to-TKR as a function of the number of HA injections. The database included 182,022 patients with knee OA who had TKR; 50,349 (27.7%) of these patients were classified as HA Users, receiving ≥1 courses of HA prior to TKR, while 131,673 patients (72.3%) were HA Non-users prior to TKR, receiving no HA. Cox proportional hazards modelling shows that TKR risk decreases as a function of the number of HA injection courses, if patient age, gender, and disease comorbidity are used as background covariates. Multiple HA injections are therefore associated with delay of TKR (all, P < 0.0001). Half of HA Non-users had a TKR by 114 days post-diagnosis of knee OA, whereas half of HA Users had a TKR by 484 days post-diagnosis (χ2 = 19,769; p < 0.0001). Patients who received no HA had a mean time-to-TKR of 0.7 years; with one course of HA, the mean time to TKR was 1.4 years (χ2 = 13,725; p < 0.0001); patients who received ≥5 courses delayed TKR by 3.6 years (χ2 = 19,935; p < 0.0001).
  
  
  CONCLUSIONS
  HA injection in patients with knee OA is associated with a dose-dependent increase in time-to-TKR.
authors.affiliation: Department of Rheumatology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Roy
authors.initials: R
authors.lastname: Altman
authors.affiliation: North American Business Unit, Seikagaku Corporation, Tokyo, Japan.
authors.forename: Sooyeol
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Medical Affairs, Bioventus LLC, Durham, NC, United States of America.
authors.forename: R Grant
authors.initials: RG
authors.lastname: Steen
authors.affiliation: Department of Orthopaedics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Vinod
authors.initials: V
authors.lastname: Dasa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019645:Arthroplasty, Replacement, Knee; D016208:Databases, Factual; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D007345:Insurance Claim Review; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000453:epidemiology; D012189:Retrospective Studies; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D006820:Hyaluronic Acid