Hyaluronate Derivatives Form

The following are hyaluronate derivatives requiring prior authorization: sodium hyaluronate (Euflexxa®, Gelsyn-3™, GenVisc®850, Hyalgan®, Supartz FX™, Synojoynt™, Triluron™, TriVisc™, VISCO-3™), hyaluronic acid (Durolane®), cross-linked hyaluronate (Gel-One®), hyaluronan (Hymovis®, Orthovisc®, Monovisc®), and hylan polymers A and B (Synvisc®, Synvisc One®).
*For Health Insurance Marketplace (HIM), coverage of hyaluronate derivatives is excluded for the pharmacy benefit and should not be approved using these criteria; these criteria may be used for medical benefit review.
FDA Approved Indication(s) Hyaluronate derivatives are indicated for the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative non-pharmacologic therapy and to simple analgesics (e.g., acetaminophen). Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that hyaluronate derivatives are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Osteoarthritis of the Knee (must meet all):

1. Diagnosis of OA of the knee supported by imaging (e.g., X-ray, MRI);
   2. Prescribed by or in consultation with a rheumatologist, orthopedist, or sports medicine physician; This prescriber requirement does not apply to New Mexico Community Care

2. Inadequate response to physical therapy as directed by a physical therapist;

   4. Failure of a ≥ 4-week trial of one of the following (a or b), as evidenced by claims history, unless all are contraindicated or clinically significant adverse effects are experienced: a. Oral non-steroidal anti-inflammatory drug (NSAID) at continuous therapeutic (prescription strength) dosing; b. Topical NSAID if member is ≥ 75 years old or unable to take oral NSAIDs; Prior authorization may be required for topical NSAIDs
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   CLINICAL POLICY Hyaluronate Derivatives

3. Trial of at least one intra-articular glucocorticoid injection with a documented positive but inadequate response (see Appendix D for examples) unless contraindicated or history of intolerance; *Prior authorization may be required for intra-articular glucocorticoids
4. If request is for a product other than Euflexxa, Monovisc, Orthovisc, Synvisc, and Synvisc One: Failure of two of the following (a, b, or c), unless clinically significant adverse effects are experienced or all are contraindicated:
   a. Euflexxa; b. Monovisc or Orthovisc; c. Synvisc or Synvisc One;
5. Member does not have any of the following: a. Coexistent active inflammatory arthritis other than OA (e.g., rheumatoid arthritis, spondylitis, gouty arthritis) in the targeted knee; b. History of total knee arthroplasty in the targeted knee;
6. Dose does not exceed one treatment cycle per knee for a 6 month period. Approval duration: 6 months (one treatment cycle per knee) (refer to section V)
   B. Other diagnoses/indications (must meet 1 or 2):
7. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, HIM-Medical Benefit) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for HIM-Medical Benefit, and CP.PMN.16 for Medicaid; or
8. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for HIM-Medical Benefit, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Osteoarthritis of the Knee (must meet all):
9. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

10. Member is responding positively to therapy as evidenced by the following, including but not limited to: a. Decrease in pain symptoms as evidenced by improvement in the Visual Analog Scale for pain; Page 2 of 11

    CLINICAL POLICY Hyaluronate Derivatives b. Improvement in ambulation or range of motion; c. Improvement in stiffness; d. Decrease in rescue pain medication use;

11. Member has not had total knee arthroplasty in the targeted knee;
    4. If request is for a product other than Euflexxa, Monovisc, Orthovisc, Synvisc, and Synvisc One: Failure of two of the following (a, b, or c), unless clinically significant adverse effects are experienced or all are contraindicated:
       a. Euflexxa; b. Monovisc or Orthovisc; c. Synvisc or Synvisc One;
12. Six or more months have elapsed since the last treatment cycle;
    6. Dose does not exceed one treatment cycle per knee. Approval duration: 6 months (one treatment cycle per knee) (refer to section V) B. Other diagnoses/indications (must meet 1 or 2):
13. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, HIM-Medical Benefit) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for HIM-Medical Benefit, and CP.PMN.16 for Medicaid; or

14. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial , HIM.PA.154 for HIM-Medical Benefit, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for HIM-Medical Benefit, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration NSAID: non-steroidal anti-inflammatory drug OA: osteoarthritis Page 3 of 11

    CLINICAL POLICY Hyaluronate Derivatives Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose Oral NSAIDs diclofenac (Voltaren)
    etodolac (Lodine) fenoprofen (Nalfon)
    ibuprofen (Motrin)
    indomethacin (Indocin) indomethacin SR (Indocin SR) ketoprofen (Orudis)
    meloxicam (Mobic)
    naproxen (Naprosyn)
    naproxen sodium (Anaprox, Anaprox DS) oxaprozin (Daypro) piroxicam (Feldene) salsalate (Disalcid) sulindac (Clinoril) tolmetin DS (Tolectin DS) 50 mg PO TID 400-500 mg PO BID 400 mg PO TID to QID 400-800 mg PO TID to QID 25-50 mg PO BID to TID 75 mg PO QD to BID 25-75 mg PO TID to QID 7.5-15 mg PO QD 250-500 mg PO BID 275-550 mg PO BID 600-1,200 mg PO BID 10-20 mg PO QD 500-750 mg PO TID, titrated up to 30,00 mg QD 150 mg-200 mg PO BID 400 mg PO TID, titrated up to 1,800 mg QD 150 mg/day 1,200 mg/day 3,200 mg/day 3,200 mg/day 200 mg/day 150 mg/day 300 mg/day 15 mg/day 1,500 mg/day 1,650 mg/day 1,800 mg/day 20 mg/day 3,000 mg/day 400 mg/day 1,800 mg/day 32 g/day 40 mg (1 mL) for large joints 40 drops QID on each painful knee 320 drops/day 2-4 g applied to affected area QID Topical NSAIDs diclofenac 1.5% (Pennsaid) Voltaren Gel 1% (diclofenac) Intra-articular glucocorticoids Kenalog (triamcinolone acetonide) Aristospan (triamcinolone hexacetonide) methylprednisolone acetate (Depo-Medrol) hydrocortisone acetate Zilretta® (triamcinolone acetonide) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. 25-50 mg for large joints 32 mg (5 mL) for large joints 75 mg/treatment 32 mg/treatment 10-20 mg for large joints 20-80 mg for large joints 80 mg/treatment 20 mg/treatment 80 mg/treatment Page 4 of 11

    CLINICAL POLICY Hyaluronate Derivatives Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Durolane, Euflexxa, Gelsyn-3, GenVisc 850, Hyalgan, Supartz FX, Synojoynt, Triluron, TriVisc, VISCO-3, Gel-One, Hymovis, Orthovisc, Monovisc, Synvisc, Synvisc One:  Known hypersensitivity to hyaluronan preparations  Patients with knee joint infections, infections or skin disease in the area of the injection site o Hymovis, Monovisc, Orthovisc: do not administer to patients with known hypersensitivity to gram positive bacterial proteins o Monovisc: do not administer to patients with known systemic bleeding disorders • Boxed warning(s): none reported Appendix D: General Information • Examples of documented positive but inadequate response to intra-articular glucocorticoid injections include but are not limited to the following: inadequate pain relief, frequent need of rescue medications such as NSAIDs or opioids, need to decrease or inability to increase activity levels, adequate pain relief but with steroid-induced hyperglycemia. • Per the 2014 and 2019 Osteoarthritis Research Society International guidelines, hyaluronate derivatives are not appropriate for multiple joint OA subtypes or joint OA other than the knee.
    o In DeGroot et al., single hyaluronic acid was compared to saline injection in a small RCT (N=64). At 6 and 12 weeks, there were no significant differences in improvement between the two groups on the American Orthopedic Foot and Ankle Society clinical rating score, the Ankle Osteoarthritis Scale score, or the patient- reported visual analog pain scale. Migliore et al., conducted a review of seven studies for ankle OA that showed mixed results, but were unable to complete a meta-analysis due to use of study design limitations (e.g., inconsistent use of primary endpoints, varying comparators, small sample size) leading to study heterogeneity. o Richette et al. conducted a multicenter, randomized, placebo-controlled trial in hip OA. At 3 months, hyaluronic acid was not more effective than placebo with a treatment difference in pain score of −0.15 (95% CI −11.04, 10.74). Responder rates were 33.3% for hyaluronic acid and 32.6% for placebo (p = 0.94). Additionally, analgesics were taken by 81% of study days by patients on placebo, and 88% of patients in the hyaluronic acid group.
    • There are no studies that have evaluated the efficacy of hyaluronate derivatives in patients with OA and coexistent other inflammatory conditions such as rheumatoid arthritis.
    • There is no data to suggest efficacy of hyaluronate derivatives in patients who have had total knee arthroplasty in the targeted knee.
    V. Dosage and Administration
    Drug Name Active Ingredient Durolane Hyaluronic acid Dose of Active Ingredient per Injection 60 mg (3 mL) Treatment Cycle* 1 injection Page 5 of 11

    CLINICAL POLICY Hyaluronate Derivatives Drug Name Active Ingredient Euflexxa Gel-One Gelsyn-3 GenVisc 850 Hyalgan Hymovis Monovisc‡ Orthovisc‡ Supartz FX Synojoynt Synvisc Synvisc One Sodium hyaluronate Cross-linked sodium hyaluronate Sodium hyaluronate Sodium hyaluronate Sodium hyaluronate (Hyalectin®) Sodium hyaluronate (HYADD®4) Cross-linked sodium hyaluronate Sodium hyaluronate Sodium hyaluronate Sodium hyaluronate Cross-linked hylan G- F 20 (hylan A and hylan B polymers) Cross-linked hylan G- F 20 (hylan A and hylan B polymers) Sodium hyaluronate
    Sodium hyaluronate
    Sodium hyaluronate Dose of Active Ingredient per Injection 20 mg (2 mL) 30 mg (3 mL) 16.8 mg (2 mL) 25 mg (2.5 mL) 20 mg (2 mL) Treatment Cycle 3 injections 1 injection 3 injections 3-5 injections 3-5 injections 24 mg (3 mL) 2 injections 88 mg (4 mL) 1 injection 30 mg (2 mL) 25 mg (2.5 mL) 20 mg (2 mL) 16 mg (2 mL) 3-4 injections 3-5 injections 3 injections 3 injections 48 mg (6 mL) 1 injection Triluron
    TriVisc
    VISCO-3 Treatment cycle: Total number of injections per cycle per knee (if treating both knees, double the number of injections per treatment cycle). ‡Per product label, one injection of Monovisc is equivalent to 3 injections of Orthovisc. 20 mg (2 mL)
    25 mg (2.5 mL)
    25 mg (2.5 mL) 3 injections
    3 injections
    3 injections VI. Product Availability
    Drug Name Durolane Euflexxa Gel-One GenVisc 850 Gelsyn-3 Hyalgan Hymovis Monovisc‡ Orthovisc‡ Supartz FX Synojoynt
    Synvisc Active Ingredient Hyaluronic acid Sodium hyaluronate Cross-linked sodium hyaluronate Sodium hyaluronate Sodium hyaluronate Sodium hyaluronate (Hyalectin®) Sodium hyaluronate (HYADD®4) Cross-linked sodium hyaluronate Sodium hyaluronate Sodium hyaluronate Sodium hyaluronate
    Cross-linked hylan G-F 20 (hylan A and hylan B polymers) Availability**
    3 mL syringe 2.25 mL syringe 3 mL syringe 3 mL syringe 2.25 mL syringe 2 mL vial or 2 mL syringe 5 mL syringe 5 mL syringe 3 mL syringe 2.5 mL syringe 3 mL syringe
    2.25 mL syringe Page 6 of 11

    CLINICAL POLICY Hyaluronate Derivatives Drug Name Synvisc One TriVisc Triluron
    Active Ingredient Cross-linked hylan G-F 20 (hylan A and hylan B polymers) Sodium hyaluronate Sodium hyaluronate
    VISCO-3 All syringes/vials are single-use (i.e., one injection/one knee); syringes are pre-filled. ‡Per product label, one injection of Monovisc is equivalent to 3 injections of Orthovisc. Sodium hyaluronate Availability
    10 mL syringe 3 mL syringe 2 mL syringe or
    2 mL vial 2.5 mL syringe VII.