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

PLoS One. 2015 Dec 22;10(12):e0145776. doi: 10.1371/journal.pone.0145776. eCollection 2015.

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.

Methods and findings: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arthroplasty, Replacement, Knee*
  • Databases, Factual*
  • Female
  • Humans
  • Hyaluronic Acid / administration & dosage*
  • Insurance Claim Review
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / epidemiology
  • Retrospective Studies
  • Time Factors
  • United States / epidemiology

Substances

  • Hyaluronic Acid

Grant support

This research was sponsored by the Seikagaku Corporation of Tokyo, Japan. Sooyeol Lim is employed by Seikagaku Corporation. Seikagaku Corporation provided support in the form of salary for author SL, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section. R. Grant Steen is employed by Bioventus LLC. Bioventus LLC provided support in the form of salary for author RGS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.