2/28/08. Member has documented symptomatic osteoarthritis of the knee substantiated by x-ray defined as:

Transcription

1 Subject: Hyaluronan Injections Original Effective Date: 2/28/08 Policy Number: MCP-046 Revision Date: 10/26/11 Review Date(s): 12/16/15; 6/15/2016; 3/21/2017, 7/10/2018 DISCLAIMER This Molina Clinical Policy (MCP) is intended to facilitate the Utilization Management process. It expresses Molina's determination as to whether certain services or supplies are medically necessary, experimental, investigational, or cosmetic for purposes of determining appropriateness of payment. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that this service or supply is covered (i.e., will be paid for by Molina) for a particular member. The member's benefit plan determines coverage. Each benefit plan defines which services are covered, which are excluded, and which are subject to dollar caps or other limits. Members and their providers will need to consult the member's benefit plan to determine if there are any exclusion(s) or other benefit limitations applicable to this service or supply. If there is a discrepancy between this policy and a member's plan of benefits, the benefits plan will govern. In addition, coverage may be mandated by applicable legal requirements of a State, the Federal government or CMS for Medicare and Medicaid members. CMS's Coverage Database can be found on the CMS website. The coverage directive(s) and criteria from an existing National Coverage Determination (NCD) or Local Coverage Determination (LCD) will supersede the contents of this Molina Clinical Policy (MCP) document and provide the directive for all Medicare members. RECOMMENDATIONS/COVERAGE CRITERIA CRITERIA FOR INITIATION OF THERAPY A single course of 3 5 weekly injections of intra-articular hyaluronan injections may be considered medically necessary for the treatment of painful osteoarthritis of the knee when ALL of the following criteria have been met: Requesting physician is one of the following specialists or member had consult with one of the following specialists: orthopedic surgeon, pain specialist, rheumatologist, or a sports medicine specialist. *Documentation of consult required. Member has documented symptomatic osteoarthritis of the knee substantiated by x-ray defined as: a. Knee pain associated with radiographic evidence of osteophytes in the knee joint, sclerosis in bone adjacent to the knee or joint space narrowing; and b. Morning stiffness of less than 30 minutes in duration or crepitus on motion of the knee Member has pain which interferes with age appropriate functional activities (e.g. ambulation, prolonged standing) Documentation of the following indicated by member s medical records, progress notes, and/or physical examination: a. Affected knee(s): Left, right or both knees* *Bilateral injections may be allowed only if both knees meet criteria. b. Pain which interferes with age appropriate functional activities (e.g. ambulation, prolonged standing) Page 1 of 9

2 c. Treatment failure of at least 3 months of the following conservatives therapies due to inadequate response, contraindication* or intolerance: *Contraindications may include: 1) Compromised GI function or at risk of GI bleeding due to the adverse events of NSAIDs, 2) Concomitant anticoagulant therapy for any condition, 3) Cardiovascular or renal risk factors precluding use of COX-2 inhibitors. i. Non-steroidal anti-inflammatory drugs (NSAIDs), and ii. Non-prescription analgesics (e.g. acetaminophen) iii. Topical capsaicin cream iv. Aspiration and intra-articular corticosteroid injections v. Non-pharmacologic treatment (e.g. weight loss, exercise, physical therapy) d. Prescriber has excluded other causes of musculoskeletal pain, including referred pain, bursitis, and inflammatory rheumatic diseases. Surgical knee replacement is not a planned treatment option at the time the intra-articular viscosupplementation is administered.* *The use of injections in an attempt to avoid knee replacement is reasonable; the use of injections in a patient for whom knee replacement is anticipated within the next year or two is not medically necessary. Member is not allergic to avian proteins, feathers and/or egg products Member has no contraindications to hyaluronan injections such as active joint infection, bleeding disorder Product requested is specifically approved by the FDA for intra-articular injection into the targeted joint. CRITERIA FOR RE-TREATMENT Refer to Duration or Scope of Services section Page 2 of 9

3 COVERAGE EXCLUSIONS All other uses of intra-articular hyaluronan injections that are not the FDA-approved indication are considered experimental, investigational and/or not medically necessary. This includes, but not limited to, the following diagnosis or treatment: 1. For any indication other than osteoarthritis 2. For treatment of osteoarthritis in any joint other than the knee 3. For treatment of patellofemoral syndrome (patellar knee pain) 4. Repeated treatment cycles within 6 months 5. Topical application of hyaluronate Contraindications/Cautions Hyaluronate products are considered not medically necessary for members with the following concomitant conditions: 1. Active inflammatory joint disease or synovitis affecting the knee, such as crystal induced synovitis, rheumatoid arthritis 2. Infection of the target joint or skin surrounding the proposed site of injection 3. Members with known hypersensitivity to hyaluronic acid preparations 4. Pregnant or nursing women 5. Children under 18 years of age SUMMARY OF EVIDENCE/POSITION STATEMENTS Hyaluronan (HA), also known as hyaluronate or hyaluronic acid, is a naturally-occurring macromolecule that is a major component of synovial fluid and is thought to contribute to its viscoelastic properties. Chemical cross-linking of hyaluronan increases its molecular weight (cross-linked hyaluronan is referred to as hylan). In osteoarthritis, the overall length of HA chains present in cartilage and the HA concentration in the synovial fluid are decreased. Intra-articular injection of HA, also referred to as viscosupplementation, is administered as a means of restoring the normal viscoelasticity of the synovial fluid in patients with osteoarthritis. In 1995, the American College of Rheumatology (ACR) published guidelines for the treatment of osteoarthritis of the knee, which recommended acetaminophen as firstline therapy, followed by low-dose ibuprofen and then full-dose non-steroidal anti-inflammatory drugs (NSAIDs), if necessary. In 2000, the ACR added viscosupplementation to its OA treatment algorithm, making this therapy a viable option along with NSAIDs, COX-2 inhibitors, and glucocorticoid injections. 9 The ACR guidelines Recommendations for the Medical Management of Osteoarthritis of the Hip and Knee list HA as an alternative approach to oral agents for patients whose non-pharmacologic therapy and treatment with acetaminophen has failed, especially if the use of NSAIDs and COX-2 inhibitors is contraindicated. 9 A Cochrane analysis published in 2005 found that at 5 to 13 weeks post-injection there was an 11 to 54 percent improvement in pain and a 9 to 15 percent improvement in function. 11 This analysis concluded that viscosupplementation is an effective treatment for OA of the knee with beneficial effects on pain, function and patient global assessment, and at different post-injection periods, but especially at the 5- to 13-week post-injection period. It should be noted that the magnitude of the clinical effect is different for different products, comparisons, time points, variables, and trial designs. However, there are few randomized head-to-head comparisons of different viscosupplements, and conclusions regarding the relative value of different products cannot be made. 11 Page 3 of 9

4 HAs are classified as medical devices rather than drugs in the U.S. At present, FDA approval of hyaluronans is limited to injection of the knee. Currently, the U.S. Food and Drug Administration (FDA) has approved five preparations of intraarticular hyaluronan as an alternative to NSAID therapy in the treatment of osteoarthritis of the knee (Synvisc, Hyalgan, Supartz, OrthoVisc, and Euflexxa ). With the exception of Euflexxa, these products are manufactured from rooster combs. Euflexxa is bioengineered through bacteria fermentation and the only non-avian derived hyaluronan approved in the U.S. Euflexxa could be especially useful in the rare patient who is allergic to avian products. HAs are indicated for the treatment of pain in OA of the knee in patients who have failed to respond adequately to conservative non-pharmacologic therapy and simple analgesics (e.g., acetaminophen). 1-5,13 In general, hyaluronan injection has comparable efficacy against NSAIDs and longer-term benefits when compared against intra-articular corticosteroids. 11 Few significant adverse events are reported with hyaluronans and the majority of adverse effects have been local reactions at the injection site. 1-5,13 It must be noted that there is a potential for allergic reactions with the rooster-derived products in patients with avian allergies. The focus of future research on HA therapy should concentrate on assessing the risks and benefits of extended treatments since there are limited data available concerning the effectiveness of multiple courses of therapy. Osteoarthritis (OA), also called degenerative joint disease and osteoarthrosis, is the most prevalent chronic joint disorder worldwide and is associated with significant pain and disability. 12 OA of the knee is progressive deterioration of the articular cartilage of the tibiofemoral and/or patellofemoral compartments. Osteoarthritis is characterized by cartilage involvement, varying from microfissures and fibrillations in early disease to virtual destruction with bone-on-bone contact in advanced disease. Osteophytes (spurs) develop at the margins of joints, and new cartilage proliferates over these bony spurs. In Western countries, radiographic evidence of OA is present in the majority of people by 65 years of age and in about 80% of those older than 75 years. Approximately 11% of people older than 64 years have symptomatic knee OA. 8 According to data from the Third National Health and Nutrition Examination Survey (NHANES, ), 37.4% of U.S. adults aged 60 years and older have radiographic OA of the knee, and 12.1% (more than 4.3 million people) have symptomatic OA of the knee. 6 Currently, no curative therapy is available for osteoarthritis, hence the overall goals of management are to reduce pain, slow disease progression, improve joint biomechanics, improve muscle strength and conditioning, delay total knee replacement, and reduce disability. 7 The management of osteoarthritic pain involves non-pharmacologic, pharmacologic, and surgical modes of therapy. Non-Pharmacologic Therapy The American College of Rheumatology (ACR) guidelines recommends non-pharmacologic therapy as initial management for OA of the knee. This includes patient and family education, support groups, weight loss, physical therapy, exercise, and occupational therapy. 9 Page 4 of 9

5 Pharmacologic Treatment Oral Therapies Pharmacologic oral therapy pain management includes acetaminophen, non-steroidal anti-inflammatory agents (NSAIDs), and cyclooxygenase type 2 (COX-2) inhibitors. 9 Acetaminophen, at doses up to 4 gram per day, is suggested as first-line therapy for mild to moderate pain and systemic treatment of symptomatic OA of the knee. A recent study concluded that 4 g per day of acetaminophen is generally well tolerated and does not result in extremely high hepatic enzyme levels in patients with OA of the knee when taken for up to 12 months with physician supervision. 10 Over-the-counter NSAIDs and topical analgesic creams are also options. The ACR guidelines recommend COX-2 inhibitors and prescription NSAIDs for moderate to severe pain. 9 However, due to the adverse effects associated with these agents, many practitioners are avoiding their long-term use. Additionally, the ACR provides no specific guidelines for the prevention and treatment of active ulcer disease and its complications in patients with osteoarthritis who are receiving NSAIDs. 9 Injection Therapy Corticosteroid injections. When oral conventional therapy fails to control symptoms or prevent disability, local steroid therapy may be an option although the role of intra-articular corticosteroids in OA remains somewhat controversial due to some reports of steroid-induced (Charcot-like) arthropathy developing after multiple injections. Individuals with a painful flare of OA of the knee may benefit from intra-articular injection of a corticosteroid such as methylprednisolone or triamcinolone. 14 Complications of intra-articular therapy have been rare. According to the American College of Rheumatology Subcommittee on OA Guidelines, trials comparing hyaluronan with intra-articular steroids found that pain relief was comparable with or greater than with steroids. Although pain relief is often achieved more slowly with hyaluronan injections than with steroids, the effect may last considerably longer with hyaluronan. Bellamy et al. conducted a systematic review using Cochrane methodology to evaluate the safety and efficacy of HA products in comparison to placebo in forty trials. Ten out of the forty trials included comparisons of intra-articular glucocorticoids. The Cochrane Review concludes that in comparison to corticosteroids and HA products, there are no statistically significant differences detected at 1 to 4 weeks post-injection; however, between 5 and 13 weeks post-injection, it noted that HA products were more effective than corticosteroids for 1 or more of the following variables: WOMAC OA Index, Lequesne Index, pain, range of motion (flexion), and number of responders. 19 Furthermore, steroid injections must be limited to 3 or 4 injections per year, given that there is an increased risk for advancing cartilage degeneration with more frequent use. 22,23 In general, compared with intraarticular corticosteroid injections, HA products seem to have a longer lasting effect even though pain relief is 11, 20, 21 achieved more slowly. Viscosupplementation HA intra-articular preparations are indicated for the treatment of pain in patients with OA of the knee whose condition has failed to adequately respond to conservative non-pharmacologic therapy and to traditional analgesics and in those for whom NSAIDs, COX-2 inhibitors, and intra-articular glucocorticoids are either contraindicated or ineffective. 1-5,13 Since analgesics have many potential significant systemic adverse effects and only control pain with no alteration in the course Page 5 of 9

6 of the disease, intra-articular hyaluronan injections are being considered earlier in the course of the OA disease process. The ACR guidelines also recommend early considerations of HA intervention. 9 More evidence has become available that supports the notion that, in addition to relieving the symptoms of OA, hyaluronans also modify the structure of the diseased joint and the rate of OA disease progression, at least early in the evolution of the disease process. 15 It should be noted that viscosupplementation does not appear to be very effective when used late in the disease process. Currently, there is no evidence that these agents reverse or retard the osteoarthritic process in the injected joints. While the indications for these products are the same, they differ with respect to physical properties, half-life within the synovium, number of injections per treatment course, and duration of effect. 1-5,24 According to a recent article published by the Academy of Managed Care Pharmacy in May 2007, The few head-to-head human clinical trials that have been published have not consistently demonstrated a clear advantage in efficacy for one product over another; however, there is some data to suggest that higher-molecular-weight HA may more efficacious. 18 Since direct comparisons of therapeutic duration have not been performed thus far, conclusions regarding the relative value of different products cannot be made at this time. 11 Surgical Intervention Various surgical procedures are used to relieve the pain and deformities caused by OA. Examples include arthroscopy and lavage to remove cartilage fragments, chondrocyte transplantation, implantation of joint spacers, reshaping of the knee bones, and knee replacement. Knee replacement is reserved for patients for whom medical management (including injection therapy) fails, and for those who have intractable pain and disability. DURATION OR SCOPE OF SERVICES INITIATION OF THERAPY Duration of Therapy and Dosage MHI will not approve the dose of an injection or the number of injections per treatment cycle which exceeds the FDA recommendations. Recommended dose and treatment cycle Note: Each three (3) or five (5) week series of individual weekly injections is considered to be one treatment cycle. Euflexxa (20mg/2ml): Once weekly for a total of 3 injections. 1 Hyalgan (20mg/2 ml): Give a total of 5 injections at weekly intervals. 2 Orthovisc (30mg/2ml): Once weekly for a total of 3 or 4 injections. If symptoms return, repeat courses may be administered. Pain relief may not occur until after the third injection. 3 Supartz (25mg/2.5 ml): Once weekly for a total of 5 injections. 4 Synvisc (16mg/2ml): Once weekly for a total of 3 injections. 5 MHI will not approve the dose of an injection or the number of injections per treatment cycle which exceeds the FDA recommended approval. Page 6 of 9

7 Administration/Utilization MHI does not consider hyaluronate injections to be a self-administered medication. HA injections should be administered by health care providers familiar and experienced in the assessment and management of patients with OA. An injection of another therapeutic agent should not be administered to the same joint at the same time a hyaluronase polymers injection is given. CONTINUATION OF THERAPY Re-Treatment Criteria A repeat series of injections will be considered on a case-by-case basis for members who have responded to the first course of injections in the following circumstances: 1. At least six (6) months have elapsed since the initial or prior treatment cycle 2. Documentation of the following : a. Significant improvement in pain and functional capacity as the result of the previous series of injections using any type of a quantification method, such as visual analog scale, joint mobility, reduction in effusion, and/or patient-response-based questionnaires b. A significant reduction in the dose/utilization of NSAIDs or other analgesics or a reduction in the number of required intra-articular corticosteroid injections during the six (6) month period following the previous series of injections c. Adverse reactions (if any) to the injections 3. In addition to the documentation required (2a-2b), the Prescriber shall submit additional medical documentation as requested by Medical Reviewer to support the need for repeat courses of treatment. Note: If the initial or prior series of injections did not prove to be beneficial to the member, MHI considers it not medically necessary to repeat the therapy and a repeat series of injections will not be approved. Coverage Exclusion In addition to the medical conditions and contraindications stated in the Coverage Exclusions section on page 2, MHI considers the following not medically necessary: 1. Additional treatment cycle(s) within 6 months following the initial or prior treatment. 2. Chronic use: injections after the second series will not be approved. Note: For the purposes of determining chronic use, the use of ANY of these agents is considered equivalent and the total number of series for all agents therefore may not exceed two. 3. Members with previous lack of response to HA therapy. Page 7 of 9

8 CODING INFORMATION CPT Description Arthrocentesis, aspiration and /or injection major joint or bursa (shoulder, hip, knee, subacromial bursa) HCPCS Q4083 Q4084 Q4085 Q4086 Description Hyaluronan or derivative, Hyalgan or Supartz, for intra-articular injection, per dose Hyaluronan or derivative, Synvisc, for intra-articular injection, per dose Hyaluronan or derivative, Euflexxa, for intra-articular injection, per dose Hyaluronan or derivative, Orthovisc, for intra-articular injection, per dose ICD-9 Code Description Osteoarthritis, localized, primary, lower leg Osteoarthritis, localized, secondary, lower leg Osteoarthritis, localized, not specified whether primary or secondary, lower leg Osteoarthritis, unspecified whether generalized or localized, lower leg ICD-10 CM Description M17.0 Bilateral primary osteoarthritis of knee M17.10 Unilateral primary osteoarthritis uns knee M17.11 Unilateral primary osteoarthritis right knee M17.12 Unilateral primary osteoarthritis left knee M17.2 Bilateral post-traumatic osteoarthritis knee M17.30 Unilateral post-traumatic osteoarthritis unspec knee M17.31 Unilateral post-traumatic osteoarthritis right knee M17.32 Unilateral post-traumatic osteoarthritis left knee M17.4 Other bilateral secondary osteoarthritis of knee M17.5 Other unilateral secondary osteoarthritis knee M17.9 Osteoarthritis of knee unspecified M17.9 Osteoarthritis of knee unspecified RESOURCE REFERENCES 1. Euflexxa [package insert]. Suffern, NY: Ferring Pharmaceuticals; February Hyalgan [package insert]. New York, NY: Sanofi-Synethelabo;July Orthovisc [package insert]. Raynham, MA: Anika Therapeutics; June Supartz [package insert]. Memphis, TN: Smith & Nephew, Inc.; February Synvisc [package insert]. Ridgefield, NJ: Genzyme Biosurgery; November Dillon CF, Rasch EK, Gu Q, Hirsch R. Prevalence of knee osteoarthritis in the United States: arthritis data from the Third National Health and Nutrition Examination Survey J Rheumatol. 2006;33: Snibbe JC, Gambardella RA. Treatment options for osteoarthritis. Orthopedics. 2005;28(suppl):S215-S220. Page 8 of 9

9 8. Manek NJ, Lane NE. Osteoarthritis: current concepts in diagnosis and management. Am Fam Physician. 2000;61: American College of Rheumatology. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000;43: Accessed on November Available at: Temple AR, Benson GD, Zinsenheim JR, Schweinle JE. Multicenter, randomized, double-blind, active-controlled, parallel-group trial of the long-term (6-12 months) safety of acetaminophen in adult patients with osteoarthritis. Clin Ther. 2006;28: Bellamy N, Campbell J, Robinson V, Gee T,Bourne R,Wells G. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2005;2: CD D Ambrosia RD. Epidemiology of osteoarthritis. Orthopedics. 2005;28(2 Suppl):s Drug Facts and Comparisons. St. Louis, MO: Facts and Comparisons Manek NJ, Lane NE. Osteoarthritis: current concepts in diagnosis and management. Am Fam Physician Mar 15;61(6): Available at: Accessed on November 4, Goldberg VM, Buckwalter JA. Hyaluronans in the treatment of osteoarthritis of the knee: evidence for diseasemodifying activity. Osteoarthritis Cartilage. 2005;13: HAYES Directory of New Medical Technologies' Status evaluation - "Sodium Hyaluronate for Osteoarthritis", (November, 1997). 17. HAYES Medical Technology Directory: Sodium Hyaluronate for Osteoarthritis, (03/04; updated 04/25/04). 18. Arnold, William M.D. Viscosupplementation: Managed Care Issues for Osteoarthritis of the Knee. Journal of Managed Care Pharmacy. Supplement: Volume 13, No. 4. Accessed on November Publication of AMCP. May Available at: Bellamy N, Campbell J, Robinson V, et al. Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006;(2): CD Altman RD, Moskowitz R. Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: a randomized clinical trial. Hyalgan Study Group. J Rheumatol. 1998;25: Kirwan JR, Rankin E. Intra-articular therapy in osteoarthritis. Baillieres Clin Rheumatol. 1997;11: Nakazawa F, Matsuno H, Watanabe Y, Katayama R, Kimura T. Corticosteroid treatment induces chondrocytes apoptosis in an experimental arthritis model and in chondrocyte cultures. Clin Exp Rhematol. 2002;20: Fubini SL, Todhunter RJ, Burton-Wurster N, Vernier-Singer M, MacLeod JN. Corticosteroids alter the differentiated phenotype of articular chondrocytes. J Orthop Res. 2001;19: Divine JG, Zazulak BT, Hewett TE. Viscosupplemntation for knee osteoarthritis: A systematic review. Clin Orthop Relat Res. 2007;455: /26/11 New evidence review was conducted by the MCP Committee. The document was approved without revision. Page 9 of 9