Comparative Effectiveness of Hyaluronic Acid Injections for Management of Knee Osteoarthritis
Condition: Knee Osteoarthritis
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Study type: Observational

Summary: 
      Osteoarthritis (OA) is a degenerative joint disease in which there is an imbalance between
      the breakdown and repair of the joint tissue. Intraarticular hyaluronic acid (HA) injections
      are used for the management of knee OA. Currently, there is limited and inconclusive evidence
      supporting use of HA injections for management of knee OA. The primary objective of our study
      is to evaluate the effectiveness of HA injections in the management of knee OA. Investigators
      will evaluate if HA injections prevent or delay knee OA surgical interventions.
    

Detailed description: 
      Osteoarthritis (OA) is a degenerative joint disease in which there is an imbalance between
      the breakdown and repair of the joint tissue.Intraarticular hyaluronic acid (HA) injections
      are used for the management of knee OA. The pooled estimates of randomized clinical trials in
      various meta-analyses do not have consistent conclusions, some conclude no benefit while
      others conclude small benefit (reducing the pain or improving the daily functioning) to
      overall benefit (alleviating pain as well as improving daily functioning).The variation in
      conclusions is due to the heterogeneity in the methodology of the clinical trials included in
      these meta-analyses as well as a difference in the interpretation of clinical
      findings.Furthermore, most of the trials (63%) evaluating efficacy of HA are industry funded,
      raising the concern for publication bias. Furthermore Although the evidence favoring the use
      of HA injections is limited, these injections still have a significant market share with an
      annual sale of $725 million per year. Given the high dollar amount spent on the intervention,
      evaluation of its effectiveness in real world setting is important. Currently, there is
      limited and inconclusive evidence supporting use of HA injections for management of knee OA.
      The primary objective of the current study is to evaluate the effectiveness of HA injections
      in the management of knee OA. Specifically, the investigators will compare the risk of any
      surgical intervention of knee as a primary outcome among the knee OA patients who are exposed
      to HA injections with those who are not exposed to HA injections (HA non-users) and those who
      are exposed to intra-articular corticosteroid (CS) injections. Three separate outcome
      definitions, which includes: i) composite surgical outcome measure (includes total knee
      replacement, partial knee replacement, arthroscopic procedures, osteotomy and free-floating
      inter-positional devices), ii) total and partial knee replacements only and iii) total knee
      replacement (TKR) only will be used to compare the effectiveness of HA users with HA
      non-users and CS users.

      This study will be conducted using knee OA patients aged 40 years and above from the Lifelink
      Plus claims data (2006-2015). Knee OA patients with a specialist visit and a recent history
      of medications used for pain management (proxy for moderate-severe pain) will be identified.
      Patients will be classified into 3 groups: 1) HA users, 2) CS users and 3) HA non-users based
      on exposure/non-exposure to these interventions within first 90 days after specialist visit.
      HA users will be matched separately with two comparison (CS users and HA non-users) groups
      using a propensity score matching approach to reduce the imbalance between the intervention
      and comparison group. HA users will be matched separately to each comparison group (1:1
      ratio) using a greedy matching approach within a predefined caliper (0.2 of the pooled
      standard deviation of the logit of the PS). Cox models will be used to compare the risk of 1)
      any surgical interventions for knee, 2) TKR and partial knee replacements only and 3) TKR
      only, among HA users and the comparison groups. For both comparisons, investigators will use
      four approaches to compare the risk of each outcome measure: 1) Unadjusted bivariate
      analysis, 2) Adjusted multivariate analysis, 3) Propensity score-matched sample and 4)
      Inverse probability weighting (IPW) using propensity score.
    

Intervention name(s): Hyaluronic Acid injections
Intervention type(s): Drug
Other intervention name(s): Synvisc, Orthovisc, Euflexxa, Monovisc, Hyglan or Supartz
Intervention MeSH terms: Hyaluronic Acid
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with a moderate to severe knee OA identified by using a specialist visit along
        with recent history of pain medication use (proxy for moderate to severe pain)
      
Keywords: Intraarticular hyaluronic acid injections; Total knee replacement; Observational study; Intraarticular corticosteroid injections; Comparative effectiveness