Pending Policies - Prescription Drugs


Viscosupplementation for Osteoarthritis

Number:RX501.049

Effective Date:04-01-2018

Coverage:

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

Medical policies are a set of written guidelines that support current standards of practice. They are based on current peer-reviewed scientific literature. A requested therapy must be proven effective for the relevant diagnosis or procedure. For drug therapy, the proposed dose, frequency and duration of therapy must be consistent with recommendations in at least one authoritative source. This medical policy is supported by FDA-approved labeling and nationally recognized authoritative references. These references include, but are not limited to: MCG care guidelines, DrugDex (IIb level of evidence or higher), NCCN Guidelines (IIb level of evidence or higher), NCCN Compendia (IIb level of evidence or higher), professional society guidelines, and CMS coverage policy.

Viscosupplementation by intra-articular (IA) injections (a single, one-time dose, injection OR multiple injections done weekly) using a U.S. Food and Drug Administration (FDA)-approved sodium hyaluronate (hyaluronic acid) (SH) preparation may be considered medically necessary for patients who meet ALL of the following DOCUMENTED criteria:

1. Symptomatic, painful osteoarthritis (OA) of the knee; AND

2. Osteophytes of the knee OR OA of the knee, confirmed by imaging; AND

3. Reports of pain interfering with functional activities (such as walking and/or standing) for a minimum of six months with morning stiffness lasting 30 minutes or less AND crepitus on knee motion;

4. Cause of pain cannot be attributed to other forms of joint disease; AND,

5. Failure to respond to a comprehensive treatment program for six months and meet any three of the following DOCUMENTED criteria:

Conservative therapy, which includes use of pharmacologic therapy (such as acetaminophen, a non-steroidal anti-inflammatory drug [NSAID] up to four times daily, topical anti-inflammatory preparations containing capsaicin cream applied to affected knee joint) for minimum of three months without functional relief, OR

Physical therapy to the affected knee joint; OR

Participation in an exercise program; OR

Utilization of an orthotic device (such as a knee brace) applied to the affected knee joint; OR

Aspiration of the affected knee joint; OR

Injection(s) of IA steroids to the same affected knee joint; OR

The patient is unable to utilize conservative therapy due to adverse effects.

Repeat treatment cycle using an FDA-approved SH preparation may be considered medically necessary for patients who meet ALL of the following DOCUMENTED criteria:

1. Six months or more have elapsed since the initial or prior treatment cycle; AND

2. Significant improvement in pain and functional capacity as a result of previous treatment cycles (e.g., reduction in use of pain relievers like NSAIDs or opioids).

Viscosupplementation by IA injections using sodium hyaluronate (SH) for the treatment of diseases of the knee that are not related to OA, including but not limited to chondromalacia patellae or osteochondritis dissecans, are considered experimental, investigational, and/or unproven.

Viscosupplementation by IA injections using SH for the treatment of OTHER joints (such as the foot, ankle, hip, spine, thumb, wrist, elbow, shoulder, and temporomandibular joint) are considered experimental, investigational, and/or unproven.

Description:

Sodium hyaluronate (SH), similar to hyaluronic acid (HA), is a sticky, viscous, elastic solution which is injected into a knee joint to ease the pain from osteoarthritis (OA). This procedure is known as viscosupplementation or intra-articular (IA) injection and is approved by the U.S. Federal Drug Administration (FDA).

Sodium hyaluronate (SH) penetrates the articular cartilage surface, the synovial tissue, and the capsule of the joints. In the normally functioning joint, the HA (a normal element of synovial fluid in the human joint) lubricates the joint during low impact activities, such as resting or walking. During high impact activities, such as running, HA helps to prevent mechanical damage and decrease shock on the joint.

There are many types of arthritis (e.g., rheumatoid, degenerative, post-traumatic, autoimmune induced). The most common form is OA, also known as degenerative joint disease (DJD). While the exact cause is unknown, there are several possible causes, including injury, age, congenital predisposition, and obesity. In patients with OA, the elasticity and viscosity of the synovial fluid and the HA concentration is reduced, and this is characterized by the breakdown of the articular cartilage within the joint. This causes a reduction of the protective, lubricating, and shock absorbing properties of the synovial fluid. By injecting SH into the joint, the normal environment of the synovial fluid is restored. Currently, there is no curative therapy for OA, and thus the overall goal of management is to reduce pain and prevent disability.

A diagnosis of knee osteoarthritis (KOA) may be determined by utilizing the following Clinical Classification Criteria from the American College of Rheumatology (ACR). (1)

Table 1. Clinical Classification Criteria

Clinical and Laboratory

Clinical and radiographic

Clinical

Positive knee pain with at least 5 of 9 symptoms below:

  • Age >50
  • Stiffness < 30 minutes.
  • Crepitus
  • Bony tenderness
  • Bony enlargement
  • No palpable warmth
  • Erythrocyte sedimentation rate (Westergren) (ESR) <40 mm/hour
  • Rheumatoid factor (RF) <1:40
  • Synovial fluid signs of OA (clear, viscous, or white blood cell count <2,000/mm3).

Positive knee pain with at least 1 of 3 symptoms below:

  • Age >50
  • Stiffness < 30 minutes
  • Crepitus
  • + osteophytes

Positive knee pain with at least 3 or 4 of 6 symptoms below:

  • Age >50
  • Stiffness < 30 minutes
  • Crepitus
  • Bony tenderness
  • Bony enlargement
  • No palpable warmth

92% sensitive

75% specific

91% sensitive

86% specific

3 of 6:

95% sensitive

69% specific

4 of 6:

84% sensitive

89% specific

Sodium hyaluronate (SH), is used as an injectable for the knee joint, and is currently marketed as Euflexxa®, Hyalgan®, Orthovisc®, Supartz™, Synvisc®, Synvisc-One™, Gel-One®, MONOVISCTM, Gel-SynTM, HYMOVIS®, or GenVisc® 850. The FDA approvals are as a medical device, not as a drug classification to treat pain in osteoarthritis (OA) of the knee joint.

For these devices, the patient must have failed to respond adequately to conservative therapy. This includes, but is not limited to, simple pain relievers, exercise, and physical therapy. The FDA approvals for SH are as follows:

Euflexxa® (Nuflexxa, Viscosup) approved on December 3, 2004 (2),

Hyalgan® (Hyaluronan, Hylan G-F20, Hylan Gel-Fluid) approved on May 28, 1997 (3),

Orthovisc® approved on February 5, 2004 (4),

Supartz™ approved on January 24, 2001 (5),

Synvisc® (Hylan G-F20) approved on August 8, 1997 (6),

Synvisc-One™ (Hylan G-F20) approved on February 26, 2009 (7),

Gel-One® approved on March 22, 2011, (8)

MONOVISCTM approved on February 25, 2014 (9),

Gel-SynTM approved on May 9, 2014 (10),

HYMOVIS® approved on August 28, 2015 (11),

GenVisc® 850 approved on September 2, 2015 (12), and

Durolane® approved in August 29, 2017 (53).

Clinical trials continue as the use of sodium hyaluronate (SH) is being investigated for treatment in the shoulder and/or hip joints; FDA approval has not been determined for these indications.

Treatment Series or Cycles:

Treatment with IA injections of SH is proven for pain due to osteoarthritis of the knee when administered according to the FDA labeled indications. (13)

Table 2. Intra-Articular Injection Cycles for Each Sodium Hyaluronate

Product

Number of injections per treatment cycle (per knee)

Euflexxa® (Nuflexxa, Viscosup)

3 injections per knee

Hyalgan® (Hyaluronan, Hylan G-F20, Hylan Gel-Fluid)

5 injections per knee

Orthovisc®

3-4 injections per knee

Supartz®

3-5 injections per knee

Synvisc® (Hylan G-F20)

3 injections per knee

Synvisc-One™ (Hylan G-F20)

1 injection per knee

Gel-One®

1 injection per knee

MONOVISCTM

1 injection per knee

Gel-SynTM

3 injections per knee

HYMOVIS®

2 injections per knee

GenVisc® 850

3-5 injections per knee

Durolane®

1 injection per knee

Rationale:

This medical policy has been updated periodically using the MEDLINE database. The most recent literature review was performed through November 2016. The following is a summary of the key literature to date.

In 1995, Scali, J.J., conducted an uncontrolled study of 75 patients with osteoarthritis (OA) of the knee who received five weekly intra-articular injections of 2-mL Hyalgan repeated every six months, for a total of 25 intra-articular (IA) injections over two years. Over the course of the study, progressive reduction was noted in various symptoms, including pain, stiffness, and analgesic intake. There were no serious systemic side effects. (14) Kolarz et al. (15) conducted an open-label, multicenter study of 108 patients who received five weekly injections of Hyalgan, 14 of whom began a new treatment cycle after four to eight months due to pain recurrence. Six of these patients completed the second cycle follow-up of 12 months. Patients who received a second treatment cycle showed further improvement. There were no significant systemic side effects. In other international studies of both Synvisc and Hyalgan, multiple treatment courses have been reported, but the studies do not permit separate assessment of the effectiveness of multiple courses of therapy.

In 2005, a Cochrane review of viscosupplementation for OA of the knee was published that evaluated a total of 63 clinical trials identified from a literature review conducted through April 2004. Overall, the review concluded hyaluronic acid (HA) is safe and effective in improving pain, function, and global patient function in the treatment of OA of the knee. Included in the 63 trials evaluated for the review were 37 trials comparing HA and/or hylan products to placebo. The pooled analyses for these 37 trials demonstrated that HA treatment was more effective than placebo, most notably in the 5 to 13 weeks after treatment. Five trials were evaluated that compared hyaluronan to nonsteroidal anti-inflammatory drugs (NSAIDs). In the analysis of this comparison, HA was found to be comparable in efficacy to NSAIDs. In nine trials comparing HA to corticosteroid injections, analysis demonstrated longer term benefits with HA than corticosteroid injections. The authors noted that the clinical effects of the HA products have considerable heterogeneity and therapeutic variability. However, conclusions about the clinical effectiveness of products could not be drawn given the limited data comparing products head-to-head. (16)

In a meta-analysis of literature, Pagnano and Westrich concluded repeat courses of HA for OA of the knee were as safe and effective as a single course of HA injections. (17) However, as noted in a 2004 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Special Report, there is no rigorous controlled evidence regarding the effectiveness of repeated treatments with HA. (18)

In 2009, the BCBSA TEC Evidence-based Practice Center published a technology assessment for the Agency for Healthcare Research and Quality (AHRQ) on the treatment of primary and secondary osteoarthritis of the knee.

The report concluded that:

Results from 42 trials (n = 5,843) generally show positive effects of viscosupplementation on pain and function scores compared to placebo for patients with primary OA of the knee. However, the evidence on viscosupplementation is accompanied by considerable uncertainty due to variable trial quality, potential publication bias, and unclear clinical significance of the changes reported.

Trials of hylan G-F 20, the highest molecular weight cross-linked product, generally reported better results than other trials.

There was no evidence for differential effects according to subgroups defined by age, sex, primary diagnosis or disease, body mass index or weight, or disease severity.

Minor adverse events accompanying IA injections are common, but the relative risk accompanying hyaluronan injections over placebo appears to be small. The risk of local adverse events appears to increase with prior courses of treatment. Pseudoseptic reactions associated with hyaluronan appear relatively uncommon but can be severe. (19)

In 2014, the BCBSA TEC completed an assessment involving a systematic review of recent meta-analyses on the treatment of knee OA with IA hyaluronan injections. (20) Included in the assessment were 5 meta-analyses published between 2011 and 2013. The meta-analyses synthesized results from trials comparing the effect of IA HA with placebo on pain and function. One attempted to carefully examine safety data noting poor reporting within the trials. Two meta-analyses arrived at the conclusion that IA HA provides a clinically meaningful benefit compared with placebo and 3 concluded that it did not, due to a lack of supportive evidence.

In contrast, several studies investigated IA viscosupplementation for OA of the hip (21-27). A systematic review of two RCTs and nine cohort studies concluded that viscosupplementation therapy with HA appears to be “a safe and effective method in the treatment of hip OA resistant to conventional treatment modalities.” However, the authors recommend future studies with a large number of patients to confirm results and to answer questions about doses, intervals between doses, and the number of injections needed to achieve a therapeutic and safe effect.

Several small RCTs, observational studies and a Cochrane Review have investigated the use of IA viscosupplementation for OA of the ankle (28-30), wrist (31), shoulder (32), and temporomandibular joint (33, 34). An industry-sponsored RCT of 660 patients with persistent shoulder pain due to glenohumeral joint OA, rotator cuff tear, and/or adhesive capsulitis compared three weekly injections versus five weekly injections of SH versus five weekly injections of saline. About 60% of patients had OA, although the majority of those with OA also had rotator cuff disorders or capsulitis. Sixty-nine percent (n=456) of the patients had a follow-up visit at 26 weeks. There was no significant difference among groups in the primary outcome measure, shoulder pain with movement at 13 weeks. Analysis of predefined, stratified subgroups revealed no significant differences in reported pain at 13 weeks, but a significant decrease in reported pain in both treatment groups at 26 weeks compared to placebo among patients with OA. In those without OA, there was no significant improvement with either regimen. Of note, this appears to be an as-treated analysis of the OA subgroup data. Differences in range of motion among groups were judged to be not clinically important.

In 2011, therapeutic trajectory following IA HA injection in knee OA was studied by Bannura et al. This meta-analysis followed 7545 participants with 54 eligible trials that evaluated IA HA verses placebo with individuals diagnosed with knee OA. The effect size favored IA HA by week 4 (0.31; 95% C l0.17, 0.45), reaching peak at week 8 (0.46; 0.28, 0.65), then trending downward, with a residual detectable effect at week 24 (0.21; 0.10, 0.31). This therapeutic trajectory was consistent among a subset of high quality trials and on multivariant analysis adjusting for correlation between time points. The study concluded IA HA is efficacious by week 4 and peaks at week 8, and exerts residual detectable results at 24 weeks. (35)

In 2011, Wang et al. evaluated the effects of Hylan G-F 20 supplementation on cartilage preservation detected by magnetic resonance imaging (MRI) in knee OA. This was a prospective, parallel, single blind clinical trial. Seventy-eight patients with symptomatic OA (Kellgren-Lawrence grade 11-111) were assigned to either intervention group (n=39 receiving 4 courses of 3 x 2.0 ml of IA Hylan g-f 20 injections in 6 month intervals) or control group (n=39 receiving usual care of knee OA without injections). MRI at baseline was completed along with evaluation at 12 months and 24 months to access overall cartilage volume and defects. Fifty-five subjects (71%) completed the final 24 month followup. Over 24 months, the intervention group had a reduced annual percentage rate of medial and lateral tibial cartilage volume loss compared with the control group. The intervention group showed reduced cartilage defect score increment in the medial tibiofemoral compartment. This study concluded that monthly IA injections of Hylan G-F 20 administered to symptomatic patients with OA has a beneficial effect on knee cartilage preservation thus warranting larger, clinical trials as a possible disease modifying agent in the treatment of knee OA. (35)

In 2012, Swiechowicz et al. evaluated IA HA injections in the treatment of primary and secondary OA of the knee. They followed a total of 113 patients (60 patients with primary OA and 53 patients with secondary OA), who were administered IA injections of HA into the affected knee. Concentration of lipid hydroperoxides in the blood plasma was obtained, along with malondialdehyde in erythrocytes. The comparable clinical improvement was observed in both forms of OA of the knee. There were beneficial changes in blood antioxidants especially in the group with secondary arthritis. (36)

In 2012, Strand et al. compared a single IA injection of Gel-200, a new cross linked formulation of HA to phosphate buffered saline for treatment of knee OA. The aim was to evaluate the safety and efficacy of a single IA injection. This was a multicenter, randomized, controlled trial in patients that exhibited symptomatic knee OA. Patients received one IA injection. Physical function (after knee aspiration), Visual Analog Scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores were completed. Patient safety in 377 patients and efficacy in 375 patients were evaluated. Effectiveness of Gel-200 by WOMAC pain subscores was statistically significant at week 13. Mean improvements from baseline in WOMAC pain subscores consistently favored Gel-200 at each visit. Effectiveness of Gel-200 treatment was statistically significant over week 3 - 13 based on WOMAC total score, physical function, and physician global evaluations. Adverse events were not significantly different between treatment groups, including serious adverse events considered related to study treatment. The trial demonstrated that a single injection of Gel 200 was well tolerated and relieved pain associated with symptomatic knee OA over 13 weeks. (37)

In 2013, Birnbaum et al. performed a random, multicenter (50 Orthopedist and Rheumatology practice sites), double blinded, and controlled trial comparing two IA HA preparations differing by their molecular weight in individuals with symptomatic knee OA. The study was designed to compare the effects of the low molecular weight (MW) HA against a well characterized intermediate MW preparation and evaluate the safety and effects of OA. Patients were randomly knee selected to receive either GO-ON (MW 800-1500 KD/2.5 ml) or Hyalgan (500-730 KD/20 mg/2 ml) at 3 week intervals. The study consisted of 217 patients in the Hyalgan group and 209 patients in the GO ON and hylan groups. The participants were treated with 3 weekly injections of intermediate MW HA. Pain scores decreased from 5.2 to 4.5 favoring Go- On, which is the higher MW product. The study determined that intermediate MW HA injections may be superior to low MW HA on knee OA symptoms lasting longer than 6 months, with similar safety. (38)

In 2013, Ostalowska et al. assessed knee function and biochemical parameters of articular fluid and peripheral blood in gonarthrosis patients following IA administration of HA. The development of gonarthrosis (GA) involves inflammatory processes. The objective of the study was to examine whether IA administration of a HA agent has any effect on the function of the knee and on the selected biochemical parameters of the articular fluid and blood in GA, as well as to demonstrate of correlation or no correlation between the effects of viscosupplementation and administration of HA into a knee containing articular fluid or a "dry" knee. The study followed 22 gonarthrosis patients who received knee HA containing articular fluid and 27 GA patients who received HA into the dry knee. HA was administered IA upon the first 3 visits held in 1 week intervals, as well as on visit 4 (12 weeks after visit 3). The study knee was assessed clinically at all visits using the OA WOMAC, visual assessment scale (VAS from 0-10) for the assessment of pain intensity and HHS questionnaire for clinical assessment of the knee function. Blood for study-related analyses was collected at initiation of the study and 12 weeks after administration of the third dose of HA. The activity of superoxide dismutase (SOD) within the articular fluid and plasma and plasma levels of malondialdehyde (MDA) was determined. The study lasted 40 weeks and involved 10 visits to the study site. Inferior WOMAC scale and quality of life was observed in patients with OA and "dry" knee, mostly due to higher joint stiffness. Following viscosupplementation treatment, improvement in all tested WOMAC scores was observed in both groups. The SOD and the MDA levels in plasma did not differ between the study groups, both before the study and after viscosupplementation. No statistically significant changes were observed in the biochemical parameters following viscosupplementation in both groups other than for reduced articular fluid MDA levels in the PS group. The study determined that viscosupplementation with HA administration is an effective method of conservative treatment in patients with GA. Its beneficial effect consists of mostly pain reduction and knee function improvement both in patients with articular fluid present within the knee and patients with dry knee joints. (39)

In 2015, Strand et al. published a systematic review and meta-analysis of randomized, saline controlled trials. (40) This was to determine the safety and efficacy of US-approved viscosupplements for symptomatic knee OA. Knee pain severity and knee joint function were assessed at 4 to 13 weeks and 14 to 26 weeks. Twenty-nine studies representing 4,866 unique patients (active: 2,673, control: 2,193) were included. Safety outcomes included serious adverse events, treatment-related serious adverse events, patient withdrawal, and adverse event-related patient withdrawal occurring at any time during follow-up. The authors concluded that “intra-articular injection of US-approved viscosupplements is safe and efficacious through 26 weeks in patients with symptomatic knee OA”.

In 2015, Zhang et al. (54) compared 2 hyaluronic acid formulations for safety and efficacy (CHASE) study in knee osteoarthritis. This was a multicenter, randomized, double-blind, 26-week non-inferiority trial comparing Durolane to Artz. Patients (N=349) from the People's Republic of China were randomized to treatment (Durolane=175, Artz=174). The Durolane group received a 3.0 ml injection at baseline, with sham skin punctures at weeks 1, 2, 3, and 4. The Artz group received one 2.5 ml injection at each of the same time points. The primary assessment tool was the Likert-type WOMAC pain scale at weeks 0, 6, 10, 14, 18, and week 26. Secondary assessments were WOMAC physical function, knee stiffness, and global self-assessment, at identical time points. Statistically-controlled analyses were non-inferiority of Durolane over 18, then over 26 weeks, with a priori non-inferiority defined as 8% of the relevant scale. Acetaminophen was permitted as rescue analgesia and all adverse events were recorded.

Overall study retention was excellent; 332 patients (95.1%) completed 18 weeks and 319 (91.4%) completed 26 weeks, with no significant retention difference between treatment arms. All variables met non-inferiority criteria over 18 and 26 weeks. Efficacy response in both arms was >90%. Treatment-related Adverse events were 9.8% (17/174) for Artz and 13.1% (23/175) for Durolane. This study concluded that a single injection of Durolane is non-inferior to 5 injections of Artz over 18 and 26 weeks for pain, physical function, global self-assessment, and knee stiffness. Both treatments were efficacious, safe, and well tolerated.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 3.

Table 3. Summary of Key Trials

NCT No.

Trial Name

Planned Enrollment

Completion Date

Ongoing

NCT01771952 (41)

Prospective, Randomized, Double Blind Evaluation of the Efficacy of a Single Dose of Synvisc-One® (6.0 cc) for the Treatment of Patellofemoral Chondromalacia

100

Jun 2015 (ongoing)

NCT02629380 (42)

Early Viscosupplementation After Partial Meniscectomy: a Double Blind, Placebo Controlled Randomized Trial

90

Mar 2016 (ongoing)

NCT02640144 (43)

The Influence of Hyaluronic Acid Injection Following Knee Arthroscopy

60

Mar 2017

NCT: national clinical trial.

Practice Guidelines and Position Statements

Osteoarthritis Research Society International (OARSI)

In 2008, OARSI published Guidelines for the Management of Hip and Knee Osteoarthritis. OARSI guidelines state that IA HA injections may be useful in patients with knee or hip OA but the injections are characterized by delayed onset, but prolonged duration of symptomatic benefit when compared to IA injections of corticosteroids. (44) In 2014, OARSI published guidelines for the non-surgical management of knee OA, regarding hyaluronic acid treatment. The OARSI guidelines offer a stance of “Uncertain” recommendation for IA HA for individuals with knee-only OA, but despite safety and efficacy concerns of IA HA raised by one meta-analysis, a number of analyses revealed positive effect sizes for pain. (45)

National Institute for Health and Clinical Excellence (NICE)

Guidelines published by the NICE does not recommend IA-HA injections for the treatment of OA because “the cost-effectiveness estimate is outside the realms of affordability” to the National Health Service. However, guideline developers state, “Overall, the evidence suggests that hyaluronan and hylan derivatives seem to be superior to placebo in terms of efficacy and quality of life outcomes in patients with OA in the knee at different post-injection periods but especially at the 5- to 13-week post-injection period.” Toxicity of IA-HA was noted to be small. The NICE summarizes those interventions that should be considered for patients with OA, given the patient’s individual needs, risks, and preferences. The core of patient education, strengthening exercises, and weight loss, if applicable may be the first approach in treating OA. The next tier is topical NSAIDS. Beyond those recommendations are adjunctive treatments, such as supports and braces, localized heat and cold applications, oral NSAIDS and other pain medications, and IA corticosteroid injections. (46) In 2014, the NICE published an update for Osteoarthritis: Care and management in adults’ guideline and the Guideline Development Group (GDG) decided that the recommendation made in the original OA guideline (CG59) remained valid. (47)

American College of Rheumatology (ACR)

The ACR published updated guidelines in 2012 that addressed OA of the hand, hip, and knee. A conditional recommendation was given for IA hyaluronan to treat OA of the knee. ACR recommends not using IA hyaluronan for OA of the hand. For OA of the hip, ACR explicitly made no recommendation regarding treatment with IA hyaluronan due to the lack of RCTs. (48)

American Academy of Orthopedic Surgeon (AAOS)

In May 2013, the AAOS published the Knee Osteoarthritis Clinical Guideline; it does not recommend the use of IA HA agents. The guideline concluded, although a few individual studies have found significant effects, the evidence did not meet their minimum threshold for clinical improvement when combined together in a meta-analysis. In May 2013, the AAOS indicated “It is important to clearly state that this CPG (Clinical Practice Guideline) is not intended as a tool for coverage determinations. Misinterpretation of the goals and position of the CPG process can result in confusion of the message to patients, clinicians, and payers with resultant deleterious effects.” (49)

The 2009 (reaffirmed 2014) AAOS Clinical Practice Guideline on glenohumeral joint osteoarthritis (50) includes a weak grade C recommendation that “The use of injectable viscosupplementation is an option when treating patients with glenohumeral [shoulder] osteoarthritis.” Grade C recommendations are based on poor-quality evidence. In this instance, the recommendation is based on a single case series of 30 patients with OA of the glenohumeral joint who received 3 weekly IA injections of Synvisc. (51) At 1, 3, and 6 months, clinically significant improvements were seen in pain, function, and quality-of-life measures.

American Medical Society for Sport Medicine (AMSSM)

The 2016 scientific statement from the AMSSM recommended IA hyaluronan for “appropriate” patients with knee osteoarthritis (OA) based on high-quality evidence. (52) Patient selection criteria include individuals age 60 and older with Kellgren-Lawrence grade 2-3 OA. The society also “suggests” IA hyaluronan for patients under age 60 with knee OA based on moderate quality indirect evidence.

Summary of Evidence

Based on current research data there are no additional studies that prompt a change to the current coverage position of this policy. Additional publications were added to support the current coverage position. In conclusion, hyaluronic acid (HA) does have some beneficial effects, although the magnitude and clinical significance of the effects may be small. Further research would be useful, such as head-to-head comparisons of the various HA products, in longer term trials and trials examining repeated courses of treatment with HA. The evidence is insufficient to determine the efficacy of hyaluronan in joints other than the knee.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

20610, 20611

HCPCS Codes

C9465, J7318, J7320, J7321, J7322, J7323, J7324, J7325, J7326, J7327, J7328, J7329, J3490

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does have a national Medicare coverage position.

A national coverage position for Medicare may have been changed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. Altman, R., Asch, E., Bloch, D., et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. August 1986; 29(8):1039-1049. PMID 3741515

2. FDA- Approval Letter. Euflexxa® (approval December 3, 2004). Prepared by the Food and Drug Administration - Center for Devices and Radiologic Health, Medical Devices. Available at <http://www.accessdata.fda.gov> (accessed - 2016 November 29).

3. FDA- Approval Letter. Hyalgan® (approval May 28, 1997). Prepared by the Food and Drug Administration - Center for Devices and Radiologic Health, Medical Devices. Available at <http://www.accessdata.fda.gov> (accessed - 2016 November 29).

4. FDA- Approval Letter. Orthovisc® (approval February 5, 2004). Prepared by the Food and Drug Administration - Center for Devices and Radiologic Health, Medical Devices. Available at <http://www.accessdata.fda.gov> (accessed - 2016 November 29).

5. FDA- Approval Letter. SupartzTM (approval January 24, 2001). Prepared by the Food and Drug Administration - Center for Devices and Radiologic Health, Medical Devices. Available at <http://www.accessdata.fda.gov> (accessed - 2016 November 29).

6. FDA- Approval Letter. Synvisc®. (approval August 8, 1997). Prepared by the Food and Drug Administration - Center for Devices and Radiologic Health, Medical Devices. Available at <http://www.accessdata.fda.gov> (accessed - 2016 November 29).

7. FDA- Approval Letter. Synvisc-OneTM. (approval February 26, 2009). Prepared by the Food and Drug Administration - Center for Devices and Radiologic Health, Medical Devices. Available at <http://www.accessdata.fda.gov> (accessed - 2016 November 29).

8. FDA- Approval Letter. Gel-One®. (approval March 22, 2011). Prepared by the Food and Drug Administration - Center for Devices and Radiologic Health, Medical Devices. Available at <http://www.accessdata.fda.gov> (accessed - 2016 November 29).

9. FDA- Approval Letter. MONOVISCTM. (approval February 25, 2014). Prepared by the Food and Drug Administration - Center for Devices and Radiologic Health, Medical Devices. Available at <http://www.accessdata.fda.gov> (accessed - 2016 November 29).

10. FDA- Approval Letter. Gel-SynTM. (approval May 9, 2014). Prepared by the Food and Drug Administration - Center for Devices and Radiologic Health, Medical Devices. Available at <http://www.accessdata.fda.gov> (accessed - 2016 November 29).

11. FDA- Approval Letter. HYMOVIS®. (approval August 28, 2015). Prepared by the Food and Drug Administration - Center for Devices and Radiologic Health, Medical Devices. Available at <http://www.accessdata.fda.gov> (accessed - 2016 November 29).

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25. Migliore, A., Massafra, U., Bizzi, E., et al. Comparative, double-blind, controlled study of intra-articular hyaluronic acid (Hyalubrix) injections versus local anesthetic in osteoarthritis of the hip. Arthritis Research and Therapy December 2009; 11(6):R183. PMID 20003205

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Policy History:

Date Reason
4/1/2018 Document updated with literature review. Coverage unchanged. Added references 53, 54
7/15/2017 Reviewed. No changes.
1/1/2017 Document updated with literature review. Coverage unchanged.
11/1/2015 Document reviewed. Removed from Repeat treatment cycle criteria “Reduction of NSAIDs usage for six months following the previous treatment cycle” and incorporated it into the following criteria “Significant improvement in pain and functional capacity as a result of previous treatment cycles (e.g. reduction in use of pain relievers like NSAID or opioids).
2/15/2014 Document updated with literature review. Removed “at rest” to the coverage criteria; Symptomatic, painful osteoarthritis (OA) of the knee at rest.
9/1/2010 Document updated with literature review. The following changes were made: (1) revision of medical necessity criteria for comprehensive treatment program for six months prior to injection treatment; and (2) viscosupplementation for osteochondritis dissecans of the knee or for osteoarthritis of other joints (such as foot, spine, thumb, wrist, elbow, and temporomandibular joint) are considered experimental, investigational, and/or unproven.
9/15/2009 Revised and updated entire document. Coverage remains conditional for the affected knee. FDA approved single injection treatment information added to policy. This policy is no longer scheduled for routine literature review and update.
9/15/2007 Revised/updated entire document
1/1/2007 New CPT/HCPCS code(s) added
8/15/2003 Revised/updated entire document
5/1/1998 New medical document

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