Clinical UM Guideline


Subject:  Hyaluronan Injections in the Knee
Guideline #:  CG-DRUG-29Current Effective Date:  04/15/2014
Status:ReviewedLast Review Date:  02/13/2014

Description

The scope of this document encompasses the use of hyaluronan or hylan G-F 20 injections for the replacement or supplementation of naturally occurring intra-articular lubricants in individuals with osteoarthritis in the knees. This is also known as viscosupplementation. Hyaluronan preparations can vary and an initial course of treatment can range from a single injection to weekly injections (seven days apart) for three to five consecutive weeks

Note: Please see the following related document(s) for additional information:

Clinical Indications

Medically Necessary:

An initial course of intra-articular injections of hyaluronan or hylan G-F 20 is considered medically necessary for the treatment of pain due to osteoarthritis of the knee when all of the following criteria are met:

  1. There is documentation of a diagnosis of osteoarthritis and there is no evidence of inflammatory arthritis (for example, rheumatoid arthritis); and
  2. There is documentation that the pain interferes with functional activities (for example, ambulation, prolonged standing); and
  3. There is documentation of failure to respond adequately to at least 3 months of conservative therapy which includes activity modification, home exercise, protective weight bearing, and analgesics (for example, acetaminophen or non-steroidal anti-inflammatory drugs [NSAIDs]) or the individual is unable to tolerate conservative therapy because of adverse side effects; and
  4. There are no contraindications to the injections (for example, active joint infection, bleeding disorder).

A repeat course of intra-articular injections of hyaluronan or hylan G-F 20 is considered medically necessary for the treatment of pain due to osteoarthritis of the knee for individuals who meet all of the following criteria:

  1. The individual met all of the criteria for an initial course of treatment; and
  2. Six (6) months, or more, have elapsed since the conclusion of the prior treatment cycle; and
  3. There is documentation that the prior course of treatment resulted in pain relief and improvement in functional status.

Not Medically Necessary:

The use of intra-articular injections of hyaluronan or hylan G-F 20 is considered not medically necessary for the treatment of pain due to osteoarthritis of the knee when the above criteria are not met and for all other knee conditions.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS 
J7321Hyaluronan or derivative, Hyalgan or Supartz, for intra-articular injection, per dose
J7323Hyaluronan or derivative, Euflexxa, for intra-articular injection, per dose
J7324Hyaluronan or derivative, Orthovisc, for intra-articular injection, per dose
J7325Hyaluronan or derivative, Synvisc or Synvisc-One, for intra-articular injection, 1 mg
J7326Hyaluronan or derivative, Gel-One, for intra-articular injection, per dose
  
ICD-9 Diagnosis[For dates of service prior to 10/01/2014]
715.16-716.96Osteoarthrosis, lower leg (all codes in this range ending with fifth digit 6)
  
ICD-10 Diagnosis[For dates of service on or after 10/01/2014]
M17.0-M17.9Osteoarthritis of knee
  
Discussion/General Information

Osteoarthritis is the degeneration of cartilage and the underlying bone within a joint. This can lead to pain and joint stiffness. The specific causes of osteoarthritis are unknown, but it is believed to be both mechanical and molecular events in the affected joint. Onset is gradual and usually begins after age 40. It is estimated that osteoarthritis affects 13.9% of adults aged 25 and older and 33.6% of adults aged 65 and older in the United States. The most prevalent osteoarthritis occurs in the knee. There is no cure for osteoarthritis and current treatment focuses on relieving symptoms and improving function. The injections are considered to be a device by the United States Food and Drug Administration (FDA) and several have been approved via the premarket approval process.

A Cochrane review by Bellamy et al in 2006 looked at the use of intra-articular corticosteroid injections for osteoarthritis of the knee. They reported on 9 trials comparing intra-articular corticosteroid injections to intra-articular hyaluronan injections for osteoarthritis in the knee. They concluded that there were no significant differences at one to four weeks post injection, but between five and thirteen weeks post injection, hyaluronan was reported to be more effective than corticosteroids.

Chevalier and colleagues (2010) reported on a prospective, randomized, double-blind study of intra-articular injection of hylan G-F 20 versus placebo in 253 individuals with symptomatic osteoarthritis in the knee. A 4-week open, repeat treatment phase study evaluated safety only. Study participants were age 40 years or older, had a diagnosis of knee osteoarthritis found on x-ray, and had continued osteoarthritic pain despite conservative treatment. A total of 232 participants completed the study; 115 in the injection group and 117 in the placebo group. The primary outcome measure was the change in baseline over 26 weeks using the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index questionnaire. The participants were followed up at 1, 3, 8, 12, 18 and 26 weeks after injection. At 26 weeks, the participants in the injection group had a 36% change in pain from baseline while the participants in the placebo group had a 25% change in pain from baseline. After the initial treatment, a total of 160 participants went on to be treated in the open, repeat injection phase. Seventy-seven participants received a second injection of hylan G-F 20 and 83 participants received a first injection of hylan G-F 20, having received placebo in the initial treatment phase. In the group receiving a second injection of hylan G-F 20, one participant experienced an adverse event related to the study treatment and 4 participants experienced adverse events related to the study procedure. For the participants who had adverse events when they previously received hylan G-F 20 in the initial treatment phase and were now receiving their second injection of hylan G-F 20 they did not experience any further adverse events on repeat exposure.

In their 2008 Clinical Practice Guidelines for the treatment of osteoarthritis of the knees, the American Academy of Orthopedic Surgeons recommended that individuals with symptomatic osteoarthritis of the knees receive acetaminophen or NSAIDs unless there are contraindications to this treatment. They could not recommend for or against the use of intra-intrarticular hyaluronan injections for individuals with mild to moderate symptomatic osteoarthritis of the knees.

In a randomized, double blinded, placebo-controlled study, Navarro-Sarabia et al (2011) reported on the safety and efficacy of repeated injections of hyaluronic acid compared to placebo over a period of 40 months. There were four treatment cycles of five weekly injections each one with a follow-up period of 6 months after the first and second cycles and 1 year long after the third and fourth cycles. The primary efficacy outcome measure was the percentage of participants who responded clinically to the Osteoarthritis Research Society International (OARSI) 2004 criteria. Participants were considered to be a responder if their pain or physical function score decreased at least 50% and at least 20mm on the visual analog scale, or if they had two of the following three findings: a decrease in pain of at least 20% or at least 10mm on the visual analog scale, a decrease in physical function of at least 20% and at least 10mm on visual analog scale, or an increase in the score of the global assessment by at least 20% and at least 10mm on the visual analog scale. Secondary outcomes were measured by the percentage of participants with clinical response according to OARSI criteria at each follow-up visit. Three hundred one participants started the trial. There were 149 participants who received treatment and 152 participants who received placebo. At the end of the study, 109 participants who received treatment completed the study and 94 participants who received placebo completed the study. The number of responders to hyaluronic acid injections increased after each treatment cycle from 71.1% to 80.5% and the number of placebo responders were 67.8% and 65.8%. The number of participants who had at least one adverse event was the same in both treatment groups.

In 2012, the American College of Rheumatology published their recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee (Hochberg, 2012). For individuals with symptomatic knee osteoarthritis they recommend an exercise program, counseling for weight loss if the individual was overweight and use of acetaminophen or NSAIDs (unless there are contraindications to these drugs).

The California Technology Assessment Forum released their 2012 document for hyaluronic acid for treatment of osteoarthritis of the knee: repeated injections and progression to knee replacement. Their conclusion was that repeated injections of intra-articular hyaluronan for the treatment of osteoarthritis of the knee is safe, effective and improves health outcomes when compared with usual care. They did note that repeated injections of hyaluronan do not improve health outcomes for progression to knee replacement or progression of disease.

The American Academy of Orthopaedic Surgeons (AAOS) updated their Clinical Practice Guideline for Treatment of Osteoarthritis of the Knee in 2013. In their recommendations, the AAOS states that they "cannot recommend using hyaluronic acid for patients with symptomatic osteoarthritis of the knee." It was noted that the recommendation was based on lack of efficacy, not on potential harm.

Definitions

Intra-articular injections: A medical procedure using a hypodermic needle to inject a substance, such as a drug, into the space between two bones.

Osteoarthritis: A degenerative condition of the joints that causes destruction of the material in the joints that absorbs shock and allows proper movement.

References

Peer Reviewed Publications:

  1. Chevalier X, Jerosch J, Goupille P, et al. Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial. Ann Rheum Dis. 2010; 69(1):113-119.
  2. Navarro-Sarabia F, Coronel P, Collantes E, et al. A 40-month multicentre, randomised placebo-controlled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project. Ann Rheum Dis. 2011; 70(11):1957-1962.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American Academy of Orthopedic Surgeons. Clinical practice guideline Treatment of Osteoarthritis of the Knee. May 2013. Available at: http://www.aaos.org/research/guidelines/TreatmentofOsteoarthritisoftheKneeGuideline.pdf. Accessed on January 15, 2014.
  2. Bellamy N, Campbell J, Welch V, et al. Intraarticular corticosteroid for osteoarthritis. Cochrane Database Syst Rev. 2006; (2): CD005328.
  3. California Technology Assessment Forum. Hyaluronic Acid for Treatment of Osteoarthritis of the Knee: Repeated Injections and Progression to Knee Replacement. February 2012. Available at: http://www.ctaf.org/sites/default/files/assessments/1424_file_HYAL_ACID_F2012.pdf. Accessed on January 15, 2014.
  4. Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012; 64(4):465-474. Available at: http://www.rheumatology.org/practice/clinical/guidelines/ACR_2012_OA_Guidelines.pdf#toolbar=1&pagemode=bookmarks. Accessed on January 15, 2014.
  5. U.S. Food and Drug Administration Premarket Notification Database. Euflexxa®. P010029. Rockville, MD: FDA. October 11, 2011. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf/p010029s008a.pdf. Accessed on January 15, 2014.
  6. U.S. Food and Drug Administration Premarket Notification Database. Gel-One®. P080020. Rockville, MD: FDA. March 22, 2011. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf8/p080020a.pdf. Accessed on January 15, 2014.
  7. U.S. Food and Drug Administration Premarket Notification Database. Orthovisc®. P030019. Rockville, MD: FDA. February 4, 2004. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf3/p030019a.pdf. Accessed on January 15, 2014.
  8. U.S. Food and Drug Administration Premarket Notification Database. Supartz®. P980044. Rockville, MD: FDA. January 24, 2001. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf/P980044a.pdf. Accessed on January 15, 2014.
  9. U.S. Food and Drug Administration Premarket Notification Database. Synvisc-One®. No. P940015. Rockville, MD: FDA. February 26, 2009. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf/P940015S012a.pdf. Accessed on January 15, 2014.
Web Sites for Additional Information
  1. Centers for Disease Control and Prevention. Arthritis. February 2011. Available at: http://www.cdc.gov/arthritis/basics/osteoarthritis.htm. Accessed on January 15, 2014.
  2. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Osteoarthritis. 2013. Available at: http://www.niams.nih.gov/Health_Info/Osteoarthritis/default.asp#7. Accessed on January 15, 2014.
Index

Euflexxa
Gel-One
High Molecular Weight Hyaluronan
Hyalgan®
Hylan G-F 20
Orthovisc
Sodium Hyaluronate
Supartz
Synvisc®
Synvisc-One
Viscosupplementation

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Reviewed02/13/2014Medical Policy & Technology Assessment Committee (MPTAC) review. Updated References.
New05/09/2013MPTAC review. Initial document development.