SODIUM HYALURONATE. Page

Transcription

1 MEDICAL POLICY SODIUM HYALURONATE Policy Number: 2015T0078T Effective Date: October 1, 2015 Table of Contents BENEFIT CONSIDERATIONS COVERAGE RATIONALE APPLICABLE CODES.. DESCRIPTION OF SERVICES... CLINICAL EVIDENCE.. U.S. FOOD AND DRUG ADMINISTRATION CENTERS FOR MEDICARE AND MEDICAID SERVICES (CMS). REFERENCES.. POLICY HISTORY/REVISION INFORMATION.. Policy History Revision Information INSTRUCTIONS FOR USE This Medical Policy provides assistance in interpreting UnitedHealthcare benefit plans. When deciding coverage, the enrollee specific document must be referenced. The terms of an enrollee's document (e.g., Certificate of Coverage (COC) or Summary Plan Description (SPD) and Medicaid State Contracts) may differ greatly from the standard benefit plans upon which this Medical Policy is based. In the event of a conflict, the enrollee's specific benefit document supersedes this Medical Policy. All reviewers must first identify enrollee eligibility, any federal or state regulatory requirements and the enrollee specific plan benefit coverage prior to use of this Medical Policy. Other Policies and Coverage Determination Guidelines may apply. UnitedHealthcare reserves the right, in its sole discretion, to modify its Policies and Guidelines as necessary. This Medical Policy is provided for informational purposes. It does not constitute medical advice. UnitedHealthcare may also use tools developed by third parties, such as the MCG Care Guidelines, to assist us in administering health benefits. The MCG Care Guidelines are intended to be used in connection with the independent professional medical judgment of a qualified health care provider and do not constitute the practice of medicine or medical advice. BENEFIT CONSIDERATIONS Page Related Policies: Autologous Chondrocyte Transplantation In The Knee Unicondylar Spacer Devices for Treatment of Pain or Disability Essential Health Benefits for Individual and Small Group: For plan years beginning on or after January 1, 2014, the Affordable Care Act of 2010 (ACA) requires fully insured non-grandfathered individual and small group plans (inside and outside of Exchanges) to provide coverage for ten categories of Essential Health Benefits ( EHBs ). Large group plans (both self-funded and fully insured), and small group ASO plans, are not subject to the requirement to offer coverage for EHBs. However, if such plans choose to provide coverage for benefits which are deemed EHBs (such as maternity benefits), the ACA requires all dollar limits on those benefits to be removed on all Grandfathered and Non-Grandfathered plans. The determination of which benefits constitute EHBs is made on a state by state basis. As such, when using this guideline, it is important to refer to the enrollee specific benefit document to determine benefit coverage

2 COVERAGE RATIONALE Treatment with intra-articular injections of sodium hyaluronate is proven and medically necessary for pain due to osteoarthritis of the knee when administered according to U.S. Food and Drug Administration (FDA) labeled indications. FDA Labeling*: Euflexxa Gel One Hyalgan Monovisc Orthovisc Supartz Synvisc Synvisc One 3 injections 1 injection 5 injections 1 injection 3 to 4 injections 3 to 5 injections 3 injections 1 injection *Hyaluronic acid preparations for the treatment of pain due to osteoarthritis of the knee are deemed therapeutically equivalent. The UnitedHealth Group National Pharmacy and Therapeutics Committee has defined as therapeutically equivalent, products that can be expected to produce essentially the same therapeutic outcome and toxicity. Note: There is no evidence that use of one intra-articular hyaluronan product is superior to another. Repeated courses of intra-articular hyaluronan injections may be considered under the following conditions: Significant pain relief was achieved with the prior course of injections; and Pain has recurred; and At least 6 months have passed since the prior course of treatment Intra-articular injections of sodium hyaluronate are proven and medically necessary for temporomandibular joint (TMJ) disc displacement and osteoarthritis. Treatment with sodium hyaluronate preparations is unproven and not medically necessary for any other indication not listed above as proven including but not limited to: Pain due to osteoarthritis in any joint other than the knee or TMJ Any other form of arthritis (including rheumatoid arthritis) Patello-femoral syndrome Chondromalacia of the knee Following total or partial knee joint replacement Increase in viscoelasticity of synovial fluid after sodium hyaluronate injection has not been demonstrated in patients with rheumatoid arthritis, and it has not been determined whether sodium hyaluronate is protective in joints affected by rheumatoid arthritis. Further studies are needed to determine the safety and durability of such treatment for patello-femoral syndrome and chondromalacia of the knee and whether it significantly delays the need for more invasive treatment, e.g. surgery, joint replacement or arthroplasty. There are no clinical studies evaluating the use of sodium hyaluronate in persons following total or partial knee joint replacement surgery. Treatment with hyaluronic acid gel preparations to improve the skin's contour and/or reduce depressions due to acne, scars, injury or wrinkles is considered cosmetic. The use of sodium hyaluronate preparations to improve the skin's contour and/or reduce 2

3 depressions in the skin due to acne, scars, injury or wrinkles improves physical appearance but does not remove or improve a functional impairment of the skin. APPLICABLE CODES The Current Procedural Terminology (CPT ) codes and Healthcare Common Procedure Coding System (HCPCS) codes listed in this policy are for reference purposes only. Listing of a service code in this policy does not imply that the service described by this code is a covered or noncovered health service. Coverage is determined by the enrollee specific benefit document and applicable laws that may require coverage for a specific service. The inclusion of a code does not imply any right to reimbursement or guarantee claims payment. Other policies and coverage determination guidelines may apply. This list of codes may not be all inclusive. CPT Code HCPCS Code J7321 J7323 J7324 J7325 J7326 J7327 J3490 Description Arthrocentesis, aspiration and/or injection, intermediate joint or bursa (eg, temporomandibular, acromioclavicular, wrist, elbow or ankle, olecranon bursa); without ultrasound guidance Arthrocentesis, aspiration and/or injection, intermediate joint or bursa (eg, temporomandibular, acromioclavicular, wrist, elbow or ankle, olecranon bursa); with ultrasound guidance, with permanent recording and reporting Arthrocentesis, aspiration and/or injection, major joint or bursa (eg, shoulder, hip, knee, subacromial bursa); without ultrasound guidance Arthrocentesis, aspiration and/or injection, major joint or bursa (eg, shoulder, hip, knee, subacromial bursa); with ultrasound guidance, with permanent recording and reporting CPT is a registered trademark of the American Medical Association. Description Hyaluronan or derivative, Hyalgan or Supartz, 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 Hyaluronan or derivative, Synvisc or Synvisc-one, for intra-articular injection, 1 mg Hyaluronan or derivative, Gel-One, for intra-articular injection, per dose Hyaluronan or derivative, Monovisc, for intra-articular injection, per dose Unclassified drugs Coding Clarification: Sodium Hyaluronate is unproven and not medically necessary for any other diagnosis not listed as proven. This also includes any other form of arthritis other than osteoarthritis of the knee and TMJ or for any other condition not included in this policy. ICD-9 Codes (Discontinued 10/01/15) The following list of codes is provided for reference purposes only. Effective October 1, 2015, the Centers for Medicare & Medicaid Services (CMS) implemented ICD-10-CM (diagnoses) and ICD- 10-PCS (inpatient procedures), replacing the ICD-9-CM diagnosis and procedure code sets. ICD-9 codes will not be accepted for services provided on or after October 1,

4 ICD-9 Diagnosis Code Description (Proven) Discontinued 10/01/ Unspecified temporomandibular joint disorders Arthralgia of temporomandibular joint Articular disc disorder (reducing or non-reducing) of temporomandibular joint Other specified temporomandibular joint disorders Primary localized osteoarthrosis, lower leg Secondary localized osteoarthrosis, lower leg Localized osteoarthrosis not specified whether primary or secondary, lower leg Osteoarthrosis, unspecified whether generalized or localized, lower leg Unspecified polyarthropathy or polyarthritis, lower leg Other specified arthropathy, lower leg Unspecified arthropathy, lower leg Pain in joint, lower leg ICD-9 Procedure Code Description Discontinued 10/01/ Injection of therapeutic substance into temporomandibular joint Injection of therapeutic substance into joint or ligament ICD-10 Codes (Effective 10/01/15) ICD-10-CM (diagnoses) and ICD-10-PCS (inpatient procedures) must be used to report services provided on or after October 1, ICD-10 codes will not be accepted for services provided prior to October 1, ICD-10 Diagnosis Code Description (Proven) Effective 10/01/15 M Enteropathic arthropathies, right knee M Enteropathic arthropathies, left knee M Enteropathic arthropathies, unspecified knee M Other specific arthropathies, not elsewhere classified, right knee M Other specific arthropathies, not elsewhere classified, left knee M Other specific arthropathies, not elsewhere classified, unspecified knee M12.9 Arthropathy, unspecified M13.0 Polyarthritis, unspecified M17.0 Bilateral primary osteoarthritis of knee M17.10 Unilateral primary osteoarthritis, unspecified knee M17.11 Unilateral primary osteoarthritis, right knee M17.12 Unilateral primary osteoarthritis, left knee M17.2 Bilateral post-traumatic osteoarthritis of knee M17.30 Unilateral post-traumatic osteoarthritis, unspecified 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 of knee M17.9 Osteoarthritis of knee, unspecified M Pain in right knee M Pain in left knee 4

5 M Pain in unspecified knee M26.60 Temporomandibular joint disorder, unspecified M26.62 Arthralgia of temporomandibular joint M26.63 Articular disc disorder of temporomandibular joint M26.69 Other specified disorders of temporomandibular joint ICD-10 Procedure Code Effective 10/01/15 3E0U33Z 3E0U3GC 3E0U36Z 3E0U37Z 3E0U3SF 3E0U3BZ 3E0U3HZ 3E0U3KZ 3E0U3NZ 3E0U3TZ Description Introduction of Anti-inflammatory into Joints, Percutaneous Approach Introduction of Other Therapeutic Substance into Joints, Percutaneous Approach Introduction of Nutritional Substance into Joints, Percutaneous Approach Introduction of Electrolytic and Water Balance Substance into Joints, Percutaneous Approach Introduction of Other Gas into Joints, Percutaneous Approach Introduction of Local Anesthetic into Joints, Percutaneous Approach Introduction of Radioactive Substance into Joints, Percutaneous Approach Introduction of Other Diagnostic Substance into Joints, Percutaneous Approach Introduction of Analgesics, Hypnotics, Sedatives into Joints, Percutaneous Approach Introduction of Destructive Agent into Joints, Percutaneous Approach DESCRIPTION OF SERVICES Sodium hyaluronate also referred to as hyaluronic acid (HA) or hyaluronan is a viscoelastic substance that occurs naturally in synovial fluid and is thought to play an important role in lubricating, protecting, and maintaining the health of articular cartilage. Sodium hyaluronate preparations are used as an intra-articular treatment for relief of pain associated with osteoarthritis (OA), with the potential for disease modification through improvement of synovial fluid quality and/or quantity. (Hayes, 2012) Hyaluronic acid preparations have been approved by the FDA as a device for the treatment of pain in osteoarthritis of the knee in patients who have not responded to exercise, physical therapy and non-prescription analgesics. Hyaluronic acid gels have also been approved by the FDA for treatment of wrinkles and other facial contouring disorders. CLINICAL EVIDENCE Numerous randomized controlled trials have investigated the utility of sodium hyaluronate for osteoarthritis of the knee as well as for temporomandibular joint arthritis and disc displacement. There is growing literature regarding the use of Synvisc Hylan G-F 20 for the treatment of osteoarthritis (OA) of the hip. However, today, FDA labeling for sodium hyaluronate is limited to osteoarthritis of the knee. Knee Osteoarthritis A systematic review and meta-analysis by Bannuru et al. (2009) compared the effectiveness of intra-articular hyaluronic acid (n=312 patients) with corticosteroids (n=294 patients) for knee osteoarthritis (OA). Of 1238 studies evaluated, 7 studies were included for meta-analysis. The authors found that intra-articular corticosteroids appeared more effective for pain relief through 5

6 week 4. At week 4 both treatments appeared equal. However, treatment effects at 8 weeks and beyond showed greater effectiveness in the hyaluronic acid group. Goldberg and Buckwalter's (2005) meta-analysis of the use of hyaluronans in the treatment of OA concluded that there is clinical evidence to support that in addition to relieving the symptoms of OA, they also modify the structure of the disease joint and the rate of OA disease progression. A prospective, multi-center, randomized, placebo controlled double-blind study by Jorgensen et al. (2010) compared the use Hyalgan (n=165) with saline (n=170) for knee osteoarthritis. Patients in each group received 5 weekly injections. During the study, 37 patients were dropped from the study for non-compliance with the study protocol leaving 298 patients (139 in Hyalgan group and 159 in the saline group). All patients were followed for 3 months after the first injection. Patients still benefiting from treatment after 3 months were followed until time to recurrence or a maximum of 1 year after the first injection. At 3 months, 53 patients in the Hyalgan group and 47 in the saline group did not respond to treatment. Mean time to recurrence was 172 days for the Hyalgan group and 204 days for the saline group. The authors found no differences between the saline and Hyalgan group. Five weekly injections of Hyalgan did not improve pain, function or use of acetaminophen at 3, 6, 9 and 12 months after treatment for knee osteoarthritis. Chevalier et al. (2010) conducted a prospective double-blind study of 253 patients to compare the use of a single 6ml intra-articular injection of hylan G-F 20 (n=123) with placebo (n=130) in patients with symptomatic knee osteoarthritis. Outcomes were measured by the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, Likert and patient global assessment (PGA) questionnaires as well as a blinded evaluator completed by the clinical observer global assessment (COGA). Patients were followed up 1, 4, 8, 12, 18 and 26 weeks after injection. Patients receiving hylan G-F 20 had greater improvements in WOMAC A pain scores and several of the secondary outcome measures (WOMAC A1, PGA and COGA), than patients receiving placebo treatment. The authors concluded that a single 6 ml intra-articular injection of hylan G-F 20 provided better pain relief over 26 weeks than placebo. In a prospective, naturalistic study by Petrella (2005), 537 patients received a 3 intra-articular injection series with Suplasyn over 3 weeks. The cohort group was followed for 6.7 years. Patients returned for consideration of a repeat injection series based on their perception of symptom severity and were eligible if their resting visual analog scale pain was > 45 mm. The three-injection series and data collection were repeated, and again, patients were given similar instructions regarding consideration of a third injection series. The mean time between first and second series was 27 +/- 7 wks. Duration of symptom control was about 6 months. These data support the potential role of intra-articular hyaluronic acid as an effective long-term therapeutic option for patients with osteoarthritis of the knee. Conrozier et al. (2009) conducted a prospective, multi-center, randomized study of 100 patients to evaluate the safety and efficacy of five dosing regimens of viscosupplementation with hylan G- F 20 in patients with symptomatic tibio-femoral osteoarthritis. Patients were randomized to receive varying dosing regimens of hylan G-F 20 (1 x 6 ml, 1 x 4 ml, 2 x 4 ml 2 weeks apart, 3 x 4 ml 1 week apart, or 3 x 2 ml 1 week apart). Patients in the 3 x 4 ml group reported the highest percentage of device-related local adverse events (30%) while patients in the 1 x 6 ml and 3 x 2 ml groups reported only 10%. Patients in the 1 x 6, 3 x 4 and 3 x 2 ml treatment groups showed the greatest improvements in the patient-rated knee osteoarthritis pain assessment visual analog score. The authors concluded that a single 6 ml injection of hylan G-F 20 may be as efficacious, and as well tolerated, as 3 x 2 ml one week apart; however, a double-blind, controlled trial is needed to confirm these data. A systematic review and meta-analysis of 54 trials reported that hyaluronic acid is efficacious for treatment of knee pain by 4 weeks, reaches its peak of effectiveness at 8 weeks, and exerts a residual detectable effect at 24 weeks (Bannuru, 2011). However, other systematic reviews and a meta-analysis reported that evidence for clinical benefit is hindered by variable quality of trials, 6

7 potential publication bias, and unclear clinical significance of some of the reported improvements. (Rutjes, 2012; Samson, 2007) A 40-month multicenter trial randomized 306 patients with knee osteoarthritis to intra-articular injection with placebo or 4 cycles of hyaluronic acid (each cycle consisted of one injection weekly for 5 weeks) and reported that repeated cycles of hyaluronic acid injection not only improved symptoms in between cycles compared with placebo, but also exerted a carryover effect for at least 1 year after the last cycle (Navarro-Sarabia, 2011). Similarly, an open-label extension study of 378 patients from a randomized double-blind placebo-controlled trial reported that a repeated series of 3 weekly intra-articular injections of bioengineered hyaluronate given 23 weeks after the initial 3-injection treatment course was safe and effective for symptom relief. (Altman, 2011) Comparative trial reported no significant differences among 3 different hyaluronic acid (HA) formulations; Orthovisc, Synvisc, and Ostenil (Juni et al., 2007). This was a multicenter, patientblind, randomized controlled trial in 660 patients with symptomatic knee OA. Patients were randomly assigned to receive 1 cycle of 3 intraarticular injections per knee of 1 of 3 preparations: a high molecular weight cross-linked hylan, a non-cross-linked medium molecular weight HA of avian origin or a non-cross-linked low molecular weight HA of bacterial origin. The primary outcome measure was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 6 months. Secondary outcome measures included local adverse events (effusions or flares) in injected knees. During months 7-12, patients were offered a second cycle of viscosupplementation. The results showed pain relief was similar in all 3 groups. The difference in changes between baseline and 6 months between hylan and the combined hyaluronic acids was 0.1 on the WOMAC pain score (95% confidence interval [95% CI] -0.2, 0.3). No relevant differences were observed in any of the secondary efficacy outcomes, and stratified analyses provided no evidence for differences in effects across different patient groups. There was a trend toward more local adverse events in the hylan group than in the HA groups during the first cycle (difference 2.2% [95% CI -2.4, 6.7]), and this trend became more pronounced during the second cycle (difference 6.4% [95% CI 0.6, 12.2]). The authors concluded that there was no evidence for a difference in efficacy between hylan and the two hyaluronic acids. Temporomandibular Joint One treatment for TMJ disorders is the injection of substances into the joint, to replace synovial fluid. Hyaluronates are one class of synovial fluid replacements. These substances are purified natural substances that have been shown to improve the pain associated with TMJ disorders. Although sodium hyaluronate has not been labeled by the FDA for use in the temporomandibular joint (TMJ), the evidence from randomized controlled trials indicates that this treatment has a beneficial effect in patients with osteoarthritis or disc disorders of the temporomandibular joint. In a comparative study by Bjornland et al. (2007), 40 patients with osteoarthritis of the TMJ were randomly divided into two groups to compare the efficacy and complications of intra-articular TMJ injections. The subjects received either two intra-articular injections with sodium hyaluronate or two intra-articular injections with corticosteroids, 14 days apart. The effect of the treatment was evaluated 14 days, 1 and 6 months after the initial injection and was based on the following measurements: pain intensity, pain localization, joint sounds, mandibular function and complications. Both groups of patients had less pain intensity at the 6-month follow-up, and there was significantly less pain intensity in the group of patients receiving sodium hyaluronate compared with corticosteroids. A decrease in crepitation was seen in both groups. In the 20 subjects receiving sodium hyaluronate both the mandibular vertical opening and protrusion increased significantly (P < 0.000). Lateral movement from the affected side increased both in subjects injected with sodium hyaluronate (P = 0.024), and those injected with corticosteroids (P = 0.042). In conclusion, this study confirms that injections in the TMJ with sodium hyaluronate or corticosteroids may reduce pain and improve function in patients with osteoarthritis. The injections were more effective in patients with only TMJ pain compared with patients suffering 7

8 from both TMJ and myofascial pain. Injection with sodium hyaluronate was significantly more effective in decreasing pain intensity than corticosteroids. In patients with TMJ pain unresponsive to analgesics, physical therapy, and occlusal adjustment, sodium hyaluronate has been shown to reduce pain and increase range of motion in the joint. This effect can be sustained for several years and appears to be equivalent to corticosteroids without the potential adverse effects associated with chronic steroid use (Gray, 1996; Bertolami, 1993). Sato et al. (2001) found that in a study of 121 patients with disc displacement without reduction who received injections of HA, had significantly improved outcomes as compared to the control group at the one and two year follow-up. Hepguler et al. (2002) found that the use of HA in patients with disk displacement with reduction was an effective treatment for reducing pain, joint sounds and signs of clinical dysfunction. In patients with degenerative TMJ pain unresponsive to analgesics, physical therapy, and occlusal adjustment, sodium hyaluronate has been shown to reduce pain and increase range of motion in the joint. This effect can be sustained for several years and appears to be equivalent to corticosteroids without the potential adverse effects associated with chronic steroid use (Gray, 1996; Bertolami, 1993). Long et al. (2009) conducted a randomized controlled trial on 120 patients to compare the outcome of inferior and superior joint space injection of sodium hyaluronate in patients with disc displacement without reduction of the temporomandibular joint (TMJ). Patients were randomized into 2 experimental groups. One group of patients received superior joint space injections of sodium hyaluronate and the other group was treated with inferior joint space injections. Patient's TMJ status and clinical symptoms were evaluated at the 3 and 6 month follow-up appointments. The clinical parameters recorded were maximal mouth opening (MMO), pain intensity on a visual analog scale (VAS), and modified Helkimo's clinical dysfunction index and analyzed with ANCOVA. Fifty of the superior and 54 of the inferior joint space injection therapy group returned for the 3 and 6 month evaluations. Both groups had improvement in the clinical parameters at the 3 and 6 month follow-ups; however, the inferior joint injection group at 3 months had a greater reduction in TMJ pain compared with the superior joint injection group. The authors concluded that inferior joint space injection with sodium hyaluronate is a valid method of treating disc displacement without reduction of TMJ and a long-term study will be needed to assess the effect of inferior joint injection on the morphologic changes of the TMJ. Firestein: Kelley's Textbook of Rheumatology, 8th ed., 2008 edition states that intra-articular injection of high-molecular-weight sodium hyaluronate may be given twice, 2 weeks apart. Use of sodium hyaluronate has been shown to have essentially the same therapeutic effect as a steroid injection without the potential adverse side effects. Shoulder A randomized, double-blind, placebo-controlled study by Chou et al. (2010) evaluated the use of sodium hyaluronate in 51 patients with rotator cuff lesions without complete tears. Patients received either weekly injections of sodium hyaluronate or normal saline for 5 weeks. Outcomes were measured using a Constant score, which measures shoulder function, and visual analog scale. The Constant score and visual analog scale improved every week throughout treatment for both groups. However the treatment group showed greater improvement. The authors concluded that subacromial injections of sodium hyaluronate may be an alternative treatment in patients with rotator cuff lesions. The study is limited by small sample size and lack of comparison to other treatments such as subacromial steroid injection. Blaine et al. (2008) conducted a double-blind randomized controlled trial of 660 patients to evaluate the use of sodium hyaluronate (Hyalgan) to treat persistent shoulder pain. Patients were equally randomized to receive either 5 weekly intra-articular injections of sodium hyaluronate, 3 weekly intra-articular injections of sodium hyaluronate followed by 2 weekly intraarticular injections of saline solution, or 5 weekly intra-articular injections of saline solution over 26 weeks. Patients were evaluated at baseline and at 7, 9, 13, 17, and 26 weeks after the initiation of treatment. Outcomes were measured by a reduction in shoulder pain during 8

9 movement in the previous 24 hours with use of a visual analog scale at the 13 week follow-up visit as well as maintenance of visual analog scale pain relief through the 26 week period. At 7 weeks, the 5 injection hyaluronate group began to show improvement; at week 17, the 3 injection hyaluronate group began to show improvement and the 5 injection hyaluronate group maintained improvement; and at 26 weeks, the 3 injection hyaluronate maintained improvement. Patients with osteoarthritis demonstrated significantly better visual analog scale shoulder pain scores after hyaluronate treatment than those without osteoarthritis. At 26 weeks, 456 patients completed the study. The most common reasons for study discontinuation were lack of efficacy (82 patients), patient withdrawal of consent (54 patients), and loss to follow-up (11 patients). There were no meaningful differences between the groups for these reasons. Although the original endpoint of pain reduction at 13 weeks was not achieved the maintenance of pain relief at 26 weeks, as a secondary endpoint, was achieved. The patients with osteoarthritis who received Hyalgan (5 or 3 injections) achieved and maintained reductions in pain and improved function by week 26. There was no difference in pain reduction for patients without osteoarthritis between the three treatment groups; however, a significant treatment effect was observed in the control group. The threeinjection option may decrease time, expenditure and discomfort associated with the injection process. The authors concluded that the use of sodium hyaluronate is effective and well tolerated for the treatment of osteoarthritis and persistent shoulder pain in patients with shoulder pain who do not achieve adequate relief with analgesics, nonsteroidal anti-inflammatory drugs, or corticosteroids and who are not candidates for surgical intervention. However, additional work is needed to determine those who might benefit more from one regimen over the other and whether these regimens may be associated with variable outcomes not fully evaluated in this study (e.g., longer-term duration of benefit). A prospective, multi-center study by Noel et al. (2009) evaluated the use of sodium hyaluronate (Hylan G-F 20 or Synvisc-One) in 33 patients with shoulder osteoarthritis and an intact rotator cuff. Baseline measurements included a visual analog score between 59 and 64 / 100 and documentation of shoulder osteoarthritis with an osteophyte at the lower part of the humeral head measuring at least 2mm along the long axis. Follow-up was 6 months. All patients received an intra-articular injection of 2ml of Hylan G-F 20 given under fluoroscopic guidance. Patients with visual analog scores between 40 and 90 received a second injection after 1 (n=7), 2 (n=4), or 3 (n=5) months. The mean VAS pain score decreased from an average of 61.2mm at baseline to 37.1mm after 3 months. Outcomes were measured utilizing visual analog scales. Twenty-nine patients completed the study; 4 dropped out due to unacceptable pain but it was not specified if these patients received one or two injections. The authors concluded that one or two intraarticular injections of Hylan GF 20 may be a valid option in patients with shoulder osteoarthritis with an osteophyte of at least 2mm on the long axis and an intact cuff. However further studies are needed to validate the results and determine the optimal treatment frequency and appropriate patient selection criteria. The study is limited by small sample size, lack of comparison to a control group and manufacturer sponsorship. A prospective study by Brander et al. (2010) evaluated the use of 2 intra-articular injections of Hylan G-F 20 in 36 patients with shoulder arthritis who had failed 3 months of standard treatment. After injection, patients had equal or greater than 20% improvement in visual analog scale scores. Seven patients reported either increased pain (n=3) at 6 months or no pain relief (n=4). Despite these results, the authors concluded that 2 injections of Hylan G-F 20 should be considered for treating shoulder arthritis. The study is limited by small sample and lack of comparison to a control group. For osteoarthritis of the shoulder, a meta-analysis of 2120 patients from 19 randomized controlled trials reported significant improvement in pain and functional scores, but not shoulder range of motion, after intra-articular hyaluronic acid injection. In comparison with steroid injection, improvement was modestly better, but the authors were concerned with significant heterogeneity and other quality issues across all studies, and they recommended that additional studies be performed. (Saito, 2010) 9

10 A nonrandomized study of 93 elderly patients with cuff tear arthropathy of the shoulder found that in the 33 patients receiving intra-articular hyaluronic acid, as compared with the rest who were controls, pain scores were significantly improved during the first 4 months as compared with the control group, but the groups were equivalent after 5 months. The authors indicate that further study is required. (Tagliafico, 2011) A double-blind, randomized, controlled multicenter trial enrolled 300 patients with GH-OA: 150 received HA and 150 received phosphate-buffered saline (PBS) in 3 weekly injections and were evaluated over 26 weeks. Primary and secondary outcome measurements were visual analog scale (VAS) for pain and the percentage of Outcome Measures in Rheumatoid Clinical Trials- Osteoarthritis Research Society International (OMERACT-OARSI) high responders. However, differences between groups did not reach statistical significance. The authors noted that, in a subset of patients with GH-OA and no concomitant shoulder pathologies, differences between VAS and OMERACT-OARSI high-responder rated between groups were 4.0mm and 8.37 percent, respectively, which reached statistical significance. Safety analyses showed comparable rates of adverse events between groups, and neither group reported serious treatment-related adverse events. A numeric advantage, but without statistical significance, was found for HA ITT patients with GH-OA. Although data for a subset of HA patients without concomitant pathologies reached statistical significance, additional randomized trials are needed to confirm the clinical implication of this outcome. (Kwon, 2013) There is a Clinical Trial on Comparative Analysis of Intra-articular Injection of Steroid and/or Sodium Hyaluronate in Adhesive Capsulitis, which has been completed but no study results are posted. The ClinicalTrials.gov Identifier is NCT , and it was last verified on December 17, The purpose of this study is to compare the efficacy of intra-articular steroid injection, sodium hyaluronate injection, a combination of the two, and placebo in the treatment of adhesive capsulitis of the shoulder. American College of Occupational and Environmental Medicine: In a guideline last updated in 2011 on shoulder disorders, the American College of Occupational and Environmental Medicine (ACOEM) did not recommend the use of intraarticular glenohumeral viscosupplementation injections citing insufficient evidence on this therapy (ACOEM, 2011). Overall, the limited evidence from these studies suggests that intra-articular injection of sodium hyaluronate has promise for relieving shoulder pain and improving function and quality of life in patients with shoulder OA. There were no serious adverse effects associated with these viscosupplements, and the treatment appears to be safe. However, the overall quality of the evidence is low due to the paucity of studies, and methodological weaknesses of the existing studies. Hip A retrospective review by Migliore and colleagues (2012) reported on 224 participants who received injections of hylan G-F 20 and who were then followed to see if total hip replacement was required. Of the study participants, 56 were classified as being candidates for total hip replacement and 168 participants were classified to not be a candidate for a total hip replacement. Following injections, 84 participants later required total hip replacement (32 of these participants came from the non-surgical candidate group), Survival time (in months) was the amount of time between start of treatment with injections and total hip replacement, if performed. Twelve month survival was achieved by 206 participants, 24 month survival was achieved by 170 participants, and five years survival was achieved by 69 participants. This study is limited by its retrospective design and lack of a control group. The authors also note that intra-articular treatment is known to have a placebo effect and additional studies are needed to gain further insight into functional and clinical improvement. A multicenter, randomized, placebo-controlled trial by Richette et al. (2009) of 85 patients with symptomatic hip osteoarthritis (pain score of >40 mm on a visual analog scale [VAS]) and a 10

11 Kellgren/Lawrence grade of 2 or 3. Patients were randomized to the hyaluronic acid (HA) group (n = 42) or placebo group (n = 43) and followed for 3 months. At 3 months, the decrease in pain score did not differ between the HA and placebo groups in the intent-to-treat analysis (mean +/- SD decrease 7.8 +/ mm with HA versus 9.1 +/ mm with placebo; P = 0.98). The authors concluded that the findings indicate that a single IA injection of HA is no more effective than placebo in treating the symptoms of hip OA. A multi-center clinical trial by Conrozier et al. (2006), evaluated 56 patients following one intraarticular injection of hylan G-F 20. The results suggest that hylan G-F 20 is an effective treatment of symptomatic osteoarthritis of the hip, particularly in less severe radiological cases. In a clinical trial by Migliore et al. (2006), 30 patients with symptomatic hip osteoarthritis were treated with hylan G-F 20 under ultrasound guidance. Lequesne index, VAS scale of hip pain, and NSAID consumption were evaluated at baseline as well as 2 and 6 months after the beginning of the treatment. The study results showed a reduction in the Lequesne index, VAS scale of hip pain, and NSAID consumption that was statistically significant to the baseline. In a systematic review by Fernandez and Ruano-Ravina (2006), a total of 8 studies, comprising clinical trials and one review were evaluated. It was concluded that HA treatment should only be used under careful supervision by the clinician and just in those cases where other treatments have failed in hip osteoarthritis. A prospective double-blind trial by Migliore et al. (2009) of 42 patients with osteoarthritis of the hip compared the use of intra-articular bacterial-derived hyaluronic acid (Hyalubrix ) (HA) with local analgesia (mepivacaine). Outcomes were measured by the Lequesne algofunctional index (grades 1 to 4), visual analog scale (VAS), and the patient's global assessment score for hip OA. Patients receive 2 monthly injections. Both groups showed improvement from baseline. However, the hyaluronic acid group showed greater improvement in Lequesne algofunctional index and VAS scores. The authors concluded that intra-articular hyaluronic acid may be a treatment option for patients with osteoarthritis of the hip. The study is limited by small sample size and lack of a control group. Use of HA has been approved in Europe for hip pain and is in clinical trials in the US. Clinical trials are also in the process for use of HA in shoulder and ankle joints in Europe. Professional Societies The American College of Rheumatology has no recommendation for the use of intraarticular hyaluronate injections for the management of OA of the hip (Hochberg, 2012). Ankle Osteoarthritis Migliore et al (2011) evaluated the effectiveness of viscosupplementation treatment of ankle OA in the current literature. A total of 7 articles concerning the efficacy of a total of 275 patients undergoing VS treatment for ankle OA were included. The authors concluded that viscosupplementation is used widely in knee OA and is included in the professional guidelines for treatment of the disease in this joint. The potential for treating OA of the ankle joint by viscosupplementation has been suggested in the literature, however, no dosing studies have been published to date, and dosing in the ankle joint remains an area for discussion. They stated that viscosupplementation could potentially provide a useful alternative in treating such patients with painful ankle OA. A study by Mei-Dan et al. (2010) evaluated the efficacy of sodium hyaluronate to treat ankle osteoarthritis in 16 patients. Patients underwent 5 weekly injections and were followed for 32 weeks. Improvement in pain was seen in 13 of the 15 patients for the duration of the study. One patient was dropped from follow-up due to unrelated surgery. Range of motion improved by 20% and there was a reduction in pain assessed by visual analog scale and ankle-hindfoot scores. The authors concluded that intra-articular injection of sodium hyaluronate for ankle osteoarthritis is a viable treatment option. The study is limited by small sample size, lack of a control group and lack of baseline data for range of motion and pain. 11

12 A case series of 51 patients with osteoarthritis of the ankle demonstrated improvement in pain, function, and balance at 6-month follow-up of 3 weekly intra-articular hyaluronic acid injections; however, the authors advised that larger controlled trials with longer follow-up are needed (Sun, 2011). A randomized study with 26 patients assigned to hyaluronic acid at 3 different single doses, or to 3 weekly injections of the lowest dose, found that after 15 weeks only those receiving 3 weekly injections had significant improvement in pain score, but there was no placebo group and the study suffered from a high dropout rate in several groups (Witteveen, 2010). A subsequent review found that while use of hyaluronic acid for ankle arthritis continues to be actively investigated, there has not been confirmation of effectiveness or determination of established dosing regimens, and significant additional study is required (Migliore, 2011). A randomized double-blind placebo-controlled trial of 64 patients with ankle osteoarthritis found that there was no significant difference in effectiveness between treatment with a single intra-articular injection of hyaluronic acid vs saline solution at both 6-week and 12-week follow-up. (DeGroot, 2012) The available studies do not provide sufficient evidence that sodium hyaluronate injection is a safe and effective treatment for ankle osteoarthritis. Rheumatoid Arthritis (RA) There is controversy regarding the underlying biological basis for use of sodium hyaluronate for the treatment of RA. There is some evidence that sodium hyaluronate inhibits synovial cell proliferation and suppresses lymphocyte proliferation, both of which occur in RA patients (Matsuno, 1999). Furthermore, sodium hyaluronate has been shown to inhibit the release of proteoglycans from articular cartilage, a finding that suggests that there may be a reduction in degeneration of the cartilage (Matsuno, 1999). In patients with osteoarthritis, sodium hyaluronate increases the viscoelasticity of synovial fluid, which plays a key role in cushioning and protecting the joint. However, an increase in viscoelasticity of synovial fluid after sodium hyaluronate injection has not been demonstrated in patients with RA, and it has not been determined whether sodium hyaluronate is protective in joints affected by RA. Wang (2002) concluded that glycosaminoglycans (Hyaluronic Acid) may be a potential cause of rheumatoid arthritis. Majeed (2004) found that the high hyaluronic acid levels correlated with early rheumatoid arthritis disease activity. Knee (RA) For rheumatoid arthritis of the knee, a meta-analysis found 5 randomized controlled trials with 720 patients that, when pooled, resulted in significant effect sizes in favor of hyaluronic acid in terms of improvement of pain and inflammation, as well as overall treatment effectiveness. However, the authors cautioned that the number and sizes of studies were small, and that several sources of bias were present, such as with regard to language, type of preparation used, and conflicting results from larger vs smaller studies. The authors urged that additional large randomized controlled trials be undertaken (Saito, 2009). Patello-Femoral Syndrome or Chondromalacia Review of the literature resulted in one study by Jiang et al. (2007) regarding the use of sodium hyaluronate for treatment of chondromalacia. This study was uncontrolled, and is insufficient to conclude that sodium hyaluronate is effective for treatment of chondromalacia. In the study, Jiang et al. explored the use of sodium hyaluronate (visco-elastic material) for joint cavity filling combined with exercise for power in the treatment of chondromalacia patellae. The experiment was carried out among 179 knees of 120 patients with knee osteoarthritis from April 2003 to May At the 90 degrees angle of knee flexion, the patella was injected with 2 ml sodium hyaluronate solution, once per week, and 5 times were taken as a course. Meanwhile, isometric exercise for strengthening medial vastus muscle was accompanied. The result showed that after 5-week exercise, the rate of excellent and good curative effects was 91.1%, and overall response rate reached 98.9%. Excellent: disappearance of knee joint pain and rigidity, free movement, 12

13 knee joint flexion > 130degrees and extension at 0 degrees in 102 knees; Good: basic disappearance of knee joint pain and rigidity, limited movement, knee joint flexion > 110degrees and extension at 0 degrees in 61 knees; Fair: occasional disappearance of knee joint pain and rigidity, recovery after rest, limited movement, knee joint flexion 90 degrees and extension at 0 degrees in 14 knees; Ineffective: no improvements of knee joint pain and rigidity after injection, severely limited movement, knee joint flexion < 90degrees and extension at 0 degrees in 2 knees. The Randomized Evaluation of the Efficacy of Synvisc-One for the Treatment of Patellofemoral Chondromalacia clinical trial is currently recruiting participants. The purpose of this study is to determine the safety and efficacy of Synvisc-One in treating patients with chondromalacia of the patella. ClinicalTrials.gov. The American College of Occupational and Environmental Medicine (ACOEM) s occupational medicine practice guideline on Knee disorders (2011) provided no recommendation on the use hyaluronic acid injections for patellofemoral joint pain because of insufficient evidence. Joint Replacement There are no clinical studies evaluating the use of sodium hyaluronate in persons following total or partial joint replacement surgery. A literature search only found a few studies with outcomes of viscosupplementation when administered as a component of a postsurgical treatment plan. The study abstracts present conflicting findings regarding this therapy for this condition. Full-text review is required to confirm abstract content and, therefore, conclusions about the safety and effectiveness of this technology cannot be made until a full assessment has been completed. (Hayes, 2013). Treatment of Skin Contours and Depressions While sodium hyaluronate can fill in contours, the presence of depressions and/or wrinkles is not a functional impairment. Use of sodium hyaluronic gel for these indications is cosmetic. Professional Societies The American College of Rheumatology (ACR) published Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies in Osteoarthritis of the Hand, Hip, and Knee. Both strong and conditional recommendations were made for OA management. Modalities conditionally recommended for the management of hand OA include instruction in joint protection techniques, provision of assistive devices, use of thermal modalities and trapeziometacarpal joint splints, and use of oral and topical nonsteroidal antiinflammatory drugs (NSAIDs), tramadol, and topical capsaicin. Nonpharmacologic modalities strongly recommended for the management of knee OA were aerobic, aquatic, and/or resistance exercises as well as weight loss for overweight patients. Nonpharmacologic modalities conditionally recommended for knee OA included medial wedge insoles for valgus knee OA, subtalar strapped lateral insoles for varus knee OA, medially directed patellar taping, manual therapy, walking aids, thermal agents, tai chi, self-management programs, and psychosocial interventions. Pharmacologic modalities conditionally recommended for the initial management of patients with knee OA included acetaminophen, oral and topical NSAIDs, tramadol, and intraarticular corticosteroid injections; intraarticular hyaluronate injections, duloxetine, and opioids were conditionally recommended in patients who had an inadequate response to initial therapy. Opioid analgesics were strongly recommended in patients who were either not willing to undergo or had contraindications for total joint arthroplasty after having failed medical therapy. Recommendations for hip OA were similar to those for the management of knee OA. (ACR, 2012). The American Academy of Orthopaedic Surgeons (AAOS): In May 2013, the American Academy of Orthopaedic Surgeons (AAOS) published the second edition of an evidence based guideline titled, Treatment of Osteoarthritis of the Knee. In these guidelines, the AAOS does not support the use of viscosupplementation for treatment of knee OA. This rationale is based on 13

14 limitations in the literature, which include variable quality of studies, a large degree of heterogeneity in outcomes, and possible publication bias. National Institute for Health and Clinical Excellence (NICE): A 2014 guidance document states that the mechanism by which hyaluronic acid exerts its therapeutic effect, if any, is not certain, and evidence for restoration of viscoelasticity is lacking. NICE concluded that intraarticular hyaluronan injections are not recommended for the treatment of osteoarthritis. The Agence d'des technologies et des modes d'intervention en sant (AETMIS) as well, reached similar conclusions to the draft NICE guidance (Dagenais, 2007). The AETMIS assessment concluded that viscosupplementation offers clinically modest relief from the symptoms of knee osteoarthritis over a period that could last up to several weeks offering safe short-term treatment. The assessment noted, however, that these conclusions are based on secondary analyses of a multitude of small primary studies of poor methodological quality. AETMIS reported that available data did not help distinguish differences in the effectiveness of any one product over the others. It was equally impossible to identify patient subgroups more likely to benefit from this treatment compared with other currently available therapeutic modalities. AETMIS concluded that, given the modest effectiveness of viscosupplementation compared with its relatively high cost and the additional professional resources required to administer it, it is not currently justified to contemplate funding viscosupplementation for all patients with osteoarthritis of the knee. The assessment noted, however, that it is possible that viscosupplementation could be offered as a last-resort treatment to patients who do not achieve pain relief from conventional therapies or for whom these are contraindicated. Agency for Healthcare Research and Quality (AHRQ): A 2009 Clinician s Guide summarized the evidence on the effectiveness and safety of viscosupplementation for osteoarthritis of the knee. AHRQ found that: Any clinical improvement attributable to viscosupplementation is likely small and not clinically meaningful Some trials suggest better clinical response to the highest molecular weight hyaluronan product, while other trials have not confirmed this finding. Overall, evidence is insufficient to demonstrate clinical benefit for the higher molecular weight products. Evidence is insufficient to determine whether the frequency of adverse events is higher with repeat injections U.S. FOOD AND DRUG ADMINISTRATION (FDA) Osteoarthritis Sodium hyaluronate has been approved and is marketed as a device for intra-articular treatment of pain due to osteoarthritis of the knee because it acts mechanically, as a lubricant, rather than by absorption into the body as would a drug. A number of different HA preparations used for viscosupplementation have been approved as devices through the FDA Premarket Approval (PMA) process. They are all classified under the same Product Code, MOZ, which is identified in the FDA database as acid, hyaluronic, intraarticular. The FDA has approved the following labeling instructions as single-treatment regimens consisting of 1, 3, 4 or 5 injections in patients who have failed conservative therapy with exercise and simple analgesics: Hyalgan: approved for 5 injections Synvisc and Euflexxa: approved for 3 injections Supartz: approved for 3-5 injections Orthovisc*: approved for 3-4 injections Synvisc One: approved as a single injection 14

15 Gel-One: approved as a single injection Monovisc: approved as a single injection Contraindications: Do not administer to patients with known hypersensitivity (allergy) to hyaluronate preparations or allergies to avian or avian-derived products (including eggs, feathers, or poultry). This contraindication does not apply to Orthovisc. Do not administer to patients with known hypersensitivity (allergy) to gram positive bacterial proteins. This contraindication applies to Orthovisc only. Do not inject sodium hyaluronate into the knees of patients with infections or skin diseases in the area of the injection site or joint. Supartz received premarket FDA approval on January 24, On January 20, 2006 the FDA approved a labeling change to modify the directions of use section to include a statement regarding the use of a course of 3 injections; previous label had not established effectiveness for less than 5 injections. Additional information is available regarding Supartz at: Accessed April 7, Synvisc-One (hylan G-F 20) received premarket approval February 26, Additional information on Synvisc-One is available at: s/recently-approveddevices/ucm htm Accessed April 7, Hyalgan received FDA premarket approval on May 28, Additional information on Hyalgan is available at: Accessed April 7, Gel-One (hyaluronan) received FDA premarket approval on March 22, Additional information on Gel-One is available at: Accessed April 7, Orthovisc High Molecular Weight Hyaluronan received FDA premarket approval on February 4, Additional information on Orthovisc is available at: Accessed April 7, Monovisc received premarket approval February 25, Monovisc is the first FDA approved single injection product comprised of hyaluronic acid (HA) which is derived from a non-animal source. Additional information on Monovisc is available at: Accessed April 7, Skin Contouring (including acne, scars and wrinkle treatments) The FDA has approved several products containing a transparent hyaluronic acid gel to improve the contours of the skin. These products are used to treat acne, scars and wrinkles on the skin by temporarily adding volume to facial tissue and restoring a smoother appearance to the face. Devices include: Restylane injectable gel received PMA approval March 25, Perlane injectable gel received PMA approval May 2, Hylaform received PMA approval April 22, Juvéderm 24HV, Juvéderm 30 & Juvéderm 30HV Gel Implants received PMA approval June 2, CENTERS FOR MEDICARE AND MEDICAID SERVICES (CMS) 15

16 Medicare does not have a National Coverage Determination (NCD) for sodium hyaluronate injections. Local Coverage Determinations (LCDs) do exist. Refer to the LCDs for Hyaluronate Polymers, Intra-articular Injections of Hyaluronan, Hyaluronan Acid Therapies for Osteoarthritis of the Knee and Viscosupplementation Therapy for Knee. (Accessed April 10, 2015) REFERENCES Altman RD, Rosen JE, Bloch DA, et al. Safety and efficacy of retreatment with a bioengineered hyaluronate for painful osteoarthritis of the knee: results of the open-label Extension Study of the FLEXX Trial. Osteoarthritis and Cartilage 2011; 19(10): American Academy of Orthopaedic Surgeons Clinical Practice Guideline on the Treatment of Osteoarthritis of the Knee (Non-Arthroplasty). Rosemont (IL): American Academy of Orthopaedic Surgeons (AAOS); Updated 2013 American College of Occupational and Environmental Medicine (ACOEM). Shoulder disorders. In: Hegmann KT, ed. Occupational medicine practice guidelines. Evaluation and management of common health problems and functional recovery in workers. 3rd ed. Elk Grove Village, IL: American College of Occupational and Environmental Medicine Agency for Healthcare Research and Quality (AHRQ). Three Treatments for Osteoarthritis of the Knee: Evidence Shows Lack of Benefit. Clinician s Guide. April, Anika Therapeutics, Inc. Orthovisc high molecular weight hyaluronan. Package Insert AML 06/05. Woburn, MA: Anika Therapeutics; February Bannuru RR, Natov NS, Obadan I, et al. Therapeutic Trajectory of Hyaluronic Acid Versus Corticosteroids in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-Analysis. Arthritis Rheum Dec 15; 61(12): Bannuru RR, Natov NS, Dasi UR, et al. Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis--meta-analysis. Osteoarthritis and Cartilage 2011; 19 (6): Bertolami CN, Gay T, Clark GT, et al. Use of sodium hyaluronate in treating temporomandibular joint disorders: a randomized, double-blind, placebo-controlled clinical trial. J Oral Maxillofac Surg. 1993; 51: Blaine T, Moskowitz R, Udell J, et al. Treatment of persistent shoulder pain with sodium hyaluronate: a randomized, controlled trial. A multicenter study. J Bone Joint Surg Am May; 90(5): Bjornland T, Gjaerum AA, Moystad A. Osteoarthritis of the temporomandibular joint: an evaluation of the effects and complications of corticosteroid injection compared with injection with sodium hyaluronate. J Oral Rehabil Aug; 34(8): Brander VA, Gomberawalla A, Chambers M, et al. Efficacy and safety of hylan G-F 20 for symptomatic glenohumeral osteoarthritis: a prospective, pilot study. PM R Apr; 2(4): Carruthers A, Carruthers J, Monheit GD, et al. Multicenter, randomized, parallel-group study of the safety and effectiveness of onabotulinumtoxina and hyaluronic acid dermal fillers (24-mg/ml smooth, cohesive gel) alone and in combination for lower facial rejuvenation. Dermatol Surg Dec; 36 Suppl 4:

17 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, doubleblind, placebo controlled trial. Ann Rheum Dis Jan; 69(1): Chou WY, Ko JY, Wang FS, et al. Effect of sodium hyaluronate treatment on rotator cuff lesions without complete tears: a randomized, double-blind, placebo-controlled study. J Shoulder Elbow Surg Jun; 19(4): Epub 2009 Dec 5. Conrozier T. Bertin P. Bailleul F. Mathieu P. Charlot J. Vignon E. Treves R. Chevalier X. Clinical response to intra-articular injections of hylan G-F 20 in symptomatic hip osteoarthritis: the OMERACT-OARSI criteria applied to the results of a pilot study. Joint, Bone, Spine: Revue du Rhumatisme. 73(6):705-9, 2006 Dec. Conrozier T, Jerosch J, Beks P, Kemper F, Euller-Ziegler L, Bailleul F, Chevalier X. Prospective, multi-centre, randomised evaluation of the safety and efficacy of five dosing regimens of viscosupplementation with hylan G-F 20 in patients with symptomatic tibio-femoral osteoarthritis: a pilot study. Arch Orthop Trauma Surg Mar; 129(3): Dagenais P, Framarin A. Viscosupplementation for the treatment of osteoarthritis of the knee. Summary Montreal, QC: Agence d'evaluation des technologies et des modes d'intervention en sante (AETMIS); July DeLorenzi C, Weinberg M, Solish N, et al. The long-term efficacy and safety of a subcutaneously injected large-particle stabilized hyaluronic acid-based gel of nonanimal origin in esthetic facial contouring. Dermatol Surg Feb; 35 Suppl 1: DeGroot H, Uzunishvili S, Weir R, Al-omari A, et al. Intra-articular injection of hyaluronic acid is not superior to saline solution injection for ankle arthritis: a randomized, double-blind, placebocontrolled study. Journal of Bone and Joint Surgery. American Volume 2012; 94(1):2-8. ECRI Institute. Hotline Service. Viscosupplementation for Treating Knee Osteoarthritis. July Fernandez Lopez JC. Ruano-Ravina A. Efficacy and safety of intraarticular hyaluronic acid in the treatment of hip osteoarthritis: a systematic review. Osteoarthritis & Cartilage. 14(12): , 2006 Dec. Firestein: Kelley's Textbook of Rheumatology, 8th ed.; Chapter 45 - Temporomandibular Joint Pain Goldberg VM, Buckwater MD. Hyaluronans in the treatment of osteoarthritis of the knee: evidence for disease modifying activity. Osteoarthritis and Cartilage March 2005; 13(3): Hayes, Inc. Hayes Health Technology Bried. Intra-Articular Injection of Non-Cross-Linked Sodium Hyaluronate for Treatment of Shoulder Osteoarthritis. July Hayes, Inc. Hayes Medical Technology Directory. Sodium Hyaluronate for Osteoarthritis. October Hayes, Inc. Hayes Medical Technology Directory. Postsurgical Viscusupplementation for Hip or Knee Conditions. July Hepguler S, Akkoc YS, Pehlivan M, et al. The efficacy of intra-articular sodium hyaluronate in patients with reducing displaced disc of the temporomandibular joint. J Oral Rehab. 2002; 29: Hochberg M., Altman R., Toupin-April K., et al. American College of Rheumatology 2012 Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies 17

18 in Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care & Research Vol. 64, No. 4, April 2012, pp Jiang G.Y., Ju Z.Q., Yang X.L., Xu Z.Q. Visco-elastic materials for joint cavity filling combined with exercise for power in the treatment of chondromalacia patellae in 120 patients. Journal of Clinical Rehabilitative Tissue Engineering Research. 11(5) (pp ), Date of Publication: 04 Feb Jørgensen A, Stengaard-Pedersen K, Simonsen O, et al. Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year. Ann Rheum Dis Jun; 69(6): Epub 2010 May 6. Juni, P, Reichenbach, S, Trelle, S, et al. Efficacy and safety of intraarticular hylan or hyaluronic acids for osteoarthritis of the knee: a randomized controlled trial. Arthritis Rheum. 2007; 56 (11): Kwon Y, Eisenberg G, Zuckerman J. Sodium hyaluronate for the treatment of chronic shoulder pain associated with glenohumeral osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled trial. Journal of Shoulder and Elbow Surgery. May 2013; 22 (5): Epub Jan. 18, Long X, Chen G, Cheng AH, Cheng Y, Deng M, Cai H, Meng Q. A randomized controlled trial of superior and inferior temporomandibular joint space injection with hyaluronic acid in treatment of anterior disc displacement without reduction. J Oral Maxillofac Surg Feb; 67(2): Majeed M. Relationship between serum hyaluronic acid level and disease activity in early rheumatoid arthritis. Ann Rheum Dis September 2004; 63(9): Matsuno H, Yudoh K, Kondo M, et al. Biochemical effect of intra-articular injections of high molecular weight hyaluronate in rheumatoid arthritis patients. Inflamm Res. 1999; 48: Mei-Dan O, Kish B, Shabat S, et al. Treatment of osteoarthritis of the ankle by intra-articular injections of hyaluronic acid: a prospective study. J Am Podiatr Med Assoc Mar-Apr; 100(2): Migliore A, Bizzi E, Massafra U, et al. The impact of treatment with hylan G-F 20 on progression to total hip arthroplasty in patients with symptomatic hip OA: a retrospective study. Curr Med Res Opin. 2012; 28(5): Migliore A, Giovannangeli F, Bizzi E, Massafra U. et al. Viscosupplementation in the management of ankle osteoarthritis: a review. Archives of Orthopaedic and Trauma Surgery 2011; 131 (1): Migliore A, Tormenta S, Martin Martin LS, et al. The symptomatic effects of intra-articular administration of hylan G-F 20 on osteoarthritis of the hip: Clinical data of 6 months follow-up. Clin Rheumatol. 2006; 25(3): Migliore A. Tormenta S. Martin Martin LS. Iannessi F. Massafra U. Carloni E. Monno D. Alimonti A. Granata M. The symptomatic effects of intra-articular administration of hylan G-F 20 on osteoarthritis of the hip: clinical data of 6 months follow-up. Clinical Rheumatology. 25(3):389-93, 2006 May. 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 Res Ther. 2009; 11(6):R183. Epub 2009 Dec 9. 18

19 National Institute for Health and Clinical Excellence (NICE). Osteoarthritis. National Clinical Guideline for the Care and Management of Osteoarthritis in Adults. London, UK: NICE Navarro-Sarabia F, Coronel P, Collantes E, et al. A 40-month multicentre, randomised placebocontrolled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project. Annals of the Rheumatic Diseases 2011;70(11): Noël E, Hardy P, Hagena FW, et al. Efficacy and safety of Hylan G-F 20 in shoulder osteoarthritis with an intact rotator cuff. Open-label prospective multicenter study. Joint Bone Spine Dec;76(6): Petrella RJ. Hyaluronic acid for the treatment of knee osteoarthritis: long-term outcomes from a naturalistic primary care experience. Am J Phys Med Rehabil Apr;84(4):278-83; quiz 284, 293. Richette P, Ravaud P, Conrozier T, Euller-Ziegler L, et al. Effect of hyaluronic acid in symptomatic hip osteoarthritis: a multicenter, randomized, placebo-controlled trial. Arthritis Rheum Mar;60(3): Rutjes AW, Juni P, da Costa BR, et al. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Annals of Internal Medicine 2012;157(3): Samson DJ, Grant MD, Ratko TA,et al. Treatment of primary and secondary osteoarthritis of the knee. Evidence Report/Technology Assessment 2007; (157): Saito S, Kotake S. Is there evidence in support of the use of intra-articular hyaluronate in treating rheumatoid arthritis of the knee? A meta-analysis of the published literature. Modern Rheumatology 2009;19 (5): Saito S, Furuya T, Kotake S. Therapeutic effects of hyaluronate injections in patients with chronic painful shoulder: a meta-analysis of randomized controlled trials. Arthritis Care & Research 2010; 62 (7): Sato S, Goto S, Kasahar T et al. Effect of pumping with injection of sodium hyaluronate and the other factors related to outcome in patients with non-reducing disk displacemt of the temporomandibular joint. Int J Oral Maxillifac Surg. 2001;30: Sun SF, Hsu CW, Sun HP, et al. The effect of three weekly intra-articular injections of hyaluronate on pain, function, and balance in patients with unilateral ankle arthritis. Journal of Bone and Joint Surgery. American Volume 2011; 93 (18): Tagliafico A, Serafini G, Sconfienza LM, et al. Ultrasound-guided viscosupplementation of subacromial space in elderly patients with cuff tear arthropathy using a high weight hyaluronic acid: prospective open-label non-randomized trial. European Radiology 2011; 21 (1): Wang JY. Glycosaminoglycans are a potential cause of rheumatoid arthritis. Proc Natl Acad Sci U S A OCT-2002; 99(22): Witteveen AG, Sierevelt IN, Blankevoort L, et al. Intra-articular sodium hyaluronate injections in the osteoarthritic ankle joint: effects, safety and dose dependency. Foot and Ankle Surgery: Official Journal of the European Society of Foot and Ankle Surgeons 2010; 16 (4):

20 POLICY HISTORY/REVISION INFORMATION Date 10/01/2015 Action/Description Updated lists of applicable codes; added language to indicate ICD-10-CM (diagnoses) and ICD-10-PCS (inpatient procedures) must be used to report services provided on or after 10/01/2015: o ICD-9 codes will not be accepted for services provided on or after 10/01/2015 o ICD-10 codes will not be accepted for services provided prior to 10/01/2015 Archived previous policy version 2015T0078S 20