LCD L39260: Hyaluronic Acid Injections for Knee Osteoarthritis

In the United States (U.S.), osteoarthritis (OA) is the most common type of arthritis and joint disorder, with the knee being the most frequently involved symptomatic joint. 7

Degenerative joint disease (usually termed OA) of the knee is a condition characterized by the progressive destruction of the articular cartilage that lines the knee joints, the subchondral bone surfaces, and synovium, accompanied by pain, immobility, and reduction in function and the ability to complete activities of daily living (ADL). 1 Knee OA is a chronic debilitating condition - predominantly occurring among the elderly - that affects a large share of the population worldwide. It is the predominant form of arthritis and the leading cause of disability in the U.S. 5

Hyaluronic acid (HA) is a component of synovial fluid, which lubricates the joint and absorbs shock. HA is a glycosaminoglycan molecule within the knee joint where it provides viscoelastic properties to synovial fluid. 3 HA is a glycosaminoglycan that occurs naturally within the synovial fluid of the knee, providing lubrication of the joint and protecting the cartilage from mechanical degradation. HA has been shown to provide anti-inflammatory and chondroprotective effects, increase proteoglycan and HA synthesis, and reduce nerve impulses and nerve sensitivity associated with OA pain. 16 HA production is generally reduced and may be of poorer quality with OA, which may exacerbate inflammation. Intra-articular HA aims to replace depleted or poor-quality HA in the joint. HA is available commercially prepared and ready for injection. HA products differ by molecular weight and cross-linkage.

HA injections reduce cartilage breakdown that results from a loss of cartilage oligomeric matrix protein and also reduces inflammatory cytokines such as interleukin-1. 7

HA is also known as Hyaluronan or Hyaluronate. Intra-articular injection of HA is also known as viscosupplementation. Viscosupplementation is the injection of an intra-articular compound made of high molecular weight fluid containing hylan products (derivative of hyaluronan) that essentially functions as a viscoelastic glycosaminoglycan. 8

Patients with OA of the knee who are not responsive to conservative treatments, may be candidates for intra-articular HA for treatment of knee OA. There are several viscosupplementation products (such as Euflexxa ® , Durolane ® , Gel-One ® , GenVisc ® 850, Gelsyn-3 ® , Hyalgan ® , Hymovis ® , Monovisc ® , Orthovisc ® , Supartz FX ® , Synvisc ® , Synvisc-One ® , SynoJoynt™, Visco-3™, TriVisc ® , and Triluron ® ) that have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of pain associated with OA of the knee who have failed to respond adequately to conservative non-pharmacologic therapy and simple analgesics (e.g., acetaminophen).

Covered Indications

Various Hyaluronan preparations (viscosupplementation) for intra-articular injections of the knee are considered reasonable and necessary when ALL of the following criteria documented in the medical record are met:

1. Symptomatic OA of the knee. Pain that interferes with functional activities (such as, ambulation and prolonged standing).

2. The diagnosis is supported by radiographic evidence of OA of the knee, for example, joint space narrowing, subchondral sclerosis, osteophytes, and subchondral cysts.

3. Trial and failure or contraindication of at least 3 months of conservative therapy:

• Non-pharmacologic therapy (e.g., physical therapy, exercise, weight management, self-management programs, knee brace, cane)

• Pharmacologic therapy (e.g., acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) (oral, topical), topical capsaicin)

4. Failure of or contraindication to intra-articular glucocorticoid injections.

For patients who have responded to a prior series, a REPEAT* series of viscosupplement therapy is considered reasonable and necessary when ALL of the following are met:

• Patient continues to meet initial criteria

• Symptoms have recurred

• Patient has experienced improvement in pain and functional capacity following the previous series of injections

• At least 6 months have elapsed since the prior series of injections

* A series is defined as a set of injections for each joint and each treatment as per the FDA prescribing information

Limitations

Services that are not reasonable and necessary and cannot be covered by Medicare are the following:

1. The dose and frequency of administration should be consistent with the FDA approved labeling. Doses and frequencies that exceed the FDA recommended dosage/frequency as per the prescribing information, are considered not reasonable and necessary and not covered by Medicare.

2. Initiation of a repeat series of treatment when at least 6 months have not elapsed since the prior series of injections is considered not reasonable and necessary and not covered.

3. It is considered not reasonable and necessary as the initial treatment of OA of the knee.

4. It is contraindicated with infections or skin disease in the area of the injection site or joint and considered not reasonable and necessary and not covered by Medicare.

5. It is contraindicated to administer these products if you are allergic to hyaluronate products.

6. A diagnosis other than OA is considered not reasonable and necessary and not covered by Medicare.

7. When there was no improvement in knee pain and functional improvement from a previous series of injections, a repeat series of injections will be considered not reasonable and necessary and will not be covered.

8. Imaging procedures for the purpose of needle guidance that may be considered reasonable and necessary are ultrasound or fluoroscopy. The documentation must support why imaging is needed for needle guidance and insertion. Other imaging modalities (e.g., computed tomography (CT) scan, magnetic resonance imaging (MRI), arthrography) for the purpose of needle guidance and insertion will be considered not reasonable and necessary and not covered by Medicare.

Kolasinski, et al. (2020) developed guidelines and recommendations for clinicians and patients in making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients’ values, preferences, and comorbidities. Many providers want the option of using HA injections when glucocorticoid injections or other interventions fail to adequately control local joint symptoms. The conditional recommendation is consistent with the use of HA injections, in the context of shared decision-making that recognizes the limited evidence of benefit of this treatment, when other alternatives have been exhausted or failed to provide satisfactory benefit. 2

Maheu, et al. (2019) conducted a literature review to determine the strength of evidence in support of the efficacy and safety of intra-articular HA , from randomized controlled trials (RCTs) and meta-analyses. The results of their analysis showed that intra-articular HA provides a moderate symptomatic benefit to knee OA patients and without major safety concerns. In fact, intra-articular HA may offer 1 of the best benefit/risk ratios among pharmacologic options, as measured by improvements in knee OA health outcomes, overall gain in quality adjusted life years and substantial delays in time to total knee replacement (TKR). They concluded by advocating for the consideration of recommending intra-articular HA injection as a treatment option in the management of knee OA, tailored by disease stage and patient phenotype. Further research efforts should focus on identification of OA patient subgroups that demonstrate a more robust response to intra-articular HA , determination of long term effects of repeat intra-articular HA injections on patient reported outcomes and TKR-sparing effect, further elucidation of disease-modifying effects, and the potential for combination therapy with other pharmacologic and non-pharmacologic therapies to optimize the management of knee OA. 3

Newberry, et al. (2015) conducted a review of the evidence that intra-articular injections of HA in individuals with degenerative joint disease (OA) of the knee improve function and quality of life (QoL) and that they delay or prevent the need for TKR, specifically for individuals age 65 and over. They concluded that RCTs enrolling older participants showed a small, statistically significant effect of HA on function and relatively few serious adverse events; however, no studies limited participation to those 65 years or older. No conclusions can be drawn from the available literature on delay or avoidance of TKR through the use of HA. Studies that can compare large numbers of treated and untreated individuals, preferably with a randomized design, are needed to answer this question. 1

The American Academy of Orthopaedic Surgeons (AAOS) Management of Osteoarthritis of the Knee (Non-Arthroplasty) Evidence-Based Clinical Practice Guideline adopted August 31, 2021 is based on a systemic review of the available scientific and clinical information and accepted approaches to treatment and/or diagnosis. Twenty-eight studies (17 high-strength and 11 moderate-strength) assessed intra-articular HA injections when compared to controls. When we differentiated high-versus low-molecular weight viscosupplementation our analyses demonstrated no significant differences among different viscosupplementation formulations. Some studies demonstrated a statistical benefit with the use of HA but could not reach the significance for a minimally clinical meaningful difference, leading to the conclusion that viscosupplementation can represent a viable option for some patients that failed other treatments when appropriately indicated. The number needed to treat to see a tangible benefit from HA was 17 patients. Furthermore, this difference was most evident at 6 weeks and 3 months. This 2021 version of this guideline found that statistically significant improvements were associated with high-molecular cross-linked HA but when compared to mid-range molecular weight, statistical significance was not maintained. This newer analysis did not demonstrate clinically relevant differences when compared to controls. However, as previous research reported benefits in their use, the group felt that a specific subset of patients might benefit from its use. The HA recommendation was downgraded to Moderate Strength of recommendation due to lack of generalized results. HA intra-articular injection(s) is not recommended for routine use in the treatment of symptomatic OA of the knee. Currently intra-articular treatments are a commonly utilized approach in treating symptomatic knee OA, hence there should be no issues implementing this recommendation as it does not influence a major change in clinical practice, and it provides further evidence to support and guide these practices. Future research in this area should embrace detailed OA characterization including sub-group analyses and OA severity stratification. 4