Description
Intra-articular (IA) injection of hyaluronan into osteoarthritic joints is proposed to improve pain and function. It is thought to replace endogenous hyaluronan, restore the viscoelastic properties of the synovial fluid. Most studies to date have assessed hyaluronan injections for knee osteoarthritis, and this is the U.S. Food and Drug Administration-approved indication. Other joints (e.g., hip, shoulder) are being investigated for IA hyaluronan treatment of osteoarthritis. 

For individuals who have osteoarthritis of the knee who receive IA hyaluronan injections, the evidence includes randomized controlled trials (RCTs) and systematic reviews of RCTs. Relevant outcomes are symptoms, functional outcomes, and treatment-related morbidity. Many RCTs have been published over the last 2 decades. While outcomes of these RCTs have been mixed, the RCT evidence base is characterized by studies showing small treatment effects of IA hyaluronan injections. In many cases, these trials are at risk of bias, and it cannot be determined with certainty whether there is a true treatment effect or whether the reported differences are due to bias. Meta-analyses of RCTs have also had mixed findings. Some meta-analyses estimating the magnitude of treatment benefit have concluded that there is no clinically significant benefit; however, others have concluded that there is a clinically significant benefit. These meta-analyses have also highlighted the limitations of this evidence base, most notably publication bias and small trial bias. For example, a 2016 meta-analysis found more than a 3-fold larger treatment effect in small trials than in larger trials (i.e., > 100 participants). Overall, given the lack of a definitive treatment benefit despite a large quantity of literature, and given the biases present in the available evidence, it is unlikely there is a treatment benefit that is clinically meaningful. Overall, given the lack of a definitive treatment benefit despite a large quantity of literature, and given the biases present in the available evidence, it is unlikely there is a treatment benefit that is clinically meaningful.  

For individuals who have osteoarthritis of joints other than the knee who receive IA hyaluronan injections, the evidence includes RCTs, systematic reviews of RCTs, and observational studies. Relevant outcomes are symptoms, functional outcomes, and treatment-related morbidity. Meta-analyses of RCTs either have not found statistically significant benefits of the procedure on health outcomes or have found benefits that were statistically, but likely not clinically, significant (e.g., 0.27-point improvement on a 10-point visual analog scale for hip osteoarthritis).   

Background 
Knee osteoarthritis (OA) is common, costly, and a cause of substantial disability. Among U.S. adults, the most common causes of disability are arthritis and rheumatic disorders. Currently, no curative therapy is available for OA, and thus the overall goals of management are to reduce pain, disability, and need for surgery.

Intra-articular injection of hyaluronan has been proposed as a means of restoring the normal viscoelasticity of the synovial fluid in patients with OA and improving pain and function. This treatment may also be called viscosupplementation. Hyaluronan is a naturally occurring macromolecule that is a major component of synovial fluid and is thought to contribute to its viscoelastic properties. Chemical crosslinking of hyaluronan increases its molecular weight; cross-linked hyaluronans are referred to as hylans. In OA, the overall length of hyaluronan chains present in cartilage and the hyaluronan concentration in the synovial fluid are decreased.

Regulatory Status  
Several preparations of intra-articular (IA) hyaluronan have been approved by the U.S. Food and Drug Administration (FDA) as an alternative to nonsteroidal anti-inflammatory drug therapy in the treatment of osteoarthritis (OA) of the knee. Please see policy verbiage, guidelines and coding section for further information.

FDA has not approved intra-articular hyaluronan for joints other than the knee. 

FDA product code: MOZ. 

Related Policies
10127 Electrical Stimulation for the Treatment of Arthritis
20121 Temporomandibular Joint Dysfunction
701117 Arthroscopic Debridement and Lavage as Treatment for Osteoarthritis of the Knee

Policy:
Coverage of hyaluronan injection is provided when the FDA-approved indications are met and there has been a trial and failure of preferred therapies.

Intra-articular hyaluronan injections may be considered MEDICALLY NECESSARY for treatment of painful osteoarthritis of the knee in patients who meet BOTH of the following criteria:

• Trial and failure, contraindication, or intolerance to two of the following: 
  • Acetaminophen 
  • Duloxetine 
  • Formulary non-steroidal anti-inflammatory drugs (e.g., ibuprofen, naproxen) 
  • Topical capsaicin 
  • Tramadol
• Trial and failure, contraindication, or intolerance to intra-articular steroid injection (e.g., methylprednisolone, triamcinolone)    

Member must try and fail preferred products before resorting to non-formulary therapies.

Repeated courses of intra-articular hyaluronan injections of the knee may be considered MEDICALLY NECESSARY under the following conditions: 

• Significant pain relief achieved with the prior course of injections
• At least 6 months have passed since completion of the prior course

The use of intra-articular hyaiuronan injections in joints other than the knee is investigational and/or unproven and therefore considered NOT MEDICALLY NECESSARY.

Policy Guidelines
The procedure may be billed using a combination of CPT codes to describe the procedure and J codes to describe the hyaluronic acid product.

20610: Arthrocentesis, aspiration and/or injection, major joint or bursa (e.g., shoulder, hip, knee joint, subacromial bursa); without ultrasound guidance
20611: With ultrasound guidance, with permanent recording and reporting

The initial office visit to initiate hyaluronan therapy may be billed using an evaluation and management CPT code; however, the use of both the arthrocentesis procedure code and an evaluation and management CPT code during subsequent visits for the sole purpose of hyaluronan injections is not routinely warranted.

The following HCPCS codes are specific to the various hyaluronan products:

C9465 Hyaluronan or derivative, Durolane or Trivisc, for intra-articular injection, per dose
J7318: Hyaluronan or derivative, durolane, for intra-articular injection, 1 mg
J7320: Hyaluronan or derivative, GenVisc 850, for intra-articular injection, 1 mg
J7321: Hyaluronan or derivative, Hyalgan, Supartz or Visco-3, for intra-articular injection, per dose
J7322: Hyaluronan or derivative, Hymovis, for intra-articular injection, 1 mg.
J7323: Hyaluronan or derivative, Euflexxa, for intra-articular injection, per dose
J7324: Hyaluronan or derivative, Orthovisc, for intra-articular injection, per dose
J7325: Hyaluronan or derivative, Synvisc or Synvisc-One, for intra-articular injection, 1 mg
J7326: Hyaluronan or derivative, Gel-One, for intra-articular injection, per dose
J7327: Hyaluronan or derivative, Monovisc, for intra-articular injection, per dose
J7328: Hyaluronan or derivative, Gel-Syn, for intra-articular injection, per dose.
J7329: Hyaluronan or derivative, trivisc, for intra-articular injection, 1 mg
J7331: Hyaluronan or derivative, SynoJoynt, for intra-articular injection, 1 mg
J7332: Hyaluronan or derivative, synojoynt, for intra-articular injection, 1 mg
J7333: Hyaluronan or derivative, visco-3, for intra-articular injection, per dose

Rationale
Assessment of efficacy for a therapeutic intervention involves a determination of whether the technology improves health outcomes. The optimal study design for this purpose is a randomized controlled trial (RCT) that includes clinically relevant measures of health outcomes. Intermediate outcome measures, also known as surrogate outcome measures, may also be adequate if there is an established link between the intermediate outcome and true health outcomes. Nonrandomized comparative studies and uncontrolled studies can sometimes provide useful information on health outcomes, but are prone to biases such as noncomparability of treatment groups, the placebo effect and variable natural history of the condition. As there are a number of RCTs on intra-articular (IA) hyaluronan for osteoarthritis (OA), this evidence review will focus on RCTs and systematic reviews.

Knee Osteoarthritis
This evidence review was originally based on a 1998 TEC Assessment on IA hyaluronan injections for OA,¹ and incorporated material from subsequent TEC Assessments and a TEC review for Agency for Healthcare Research and Quality (AHRQ).^2,3,4 The 2007 AHRQ report concluded that results from 42 generally showed positive effects of viscosupplementation on pain and function scores compared with placebo for patients with primary OA of the knee.³ However, the evidence on viscosupplementation was accompanied by considerable uncertainty due to variable trial quality, potential publication bias and unclear clinical significance of the changes reported. Trials of hylan G-F 20 (Synvisc, 6000 kDa), the highest molecular weight cross-linked product, generally reported better results than other trials.

The 2014 TEC Assessment involved a systematic review of recent meta-analyses on the treatment of knee OA with IA hyaluronan injections.⁴ Included in the assessment were 5 meta-analyses published between 2011 and 2013.^5,6,7,8,9 Two meta-analyses concluded that IA hyaluronan provides a clinically meaningful benefit and 3 concluded that it did not, due to a lack of supportive evidence. It was not possible from the data to determine the proportions of patients achieving clinically meaningful improvement, although the analysis from the American Academy of Orthopaedic Surgeons determined that is was unlikely that an appreciable number of patients would benefit compared with placebo. It is also possible that the results supporting a clinically meaningful benefit were biased in favor of IA hyaluronan, due to unpublished trial data. When results from unpublished trials were obtained, the magnitude of treatment effect was notably lower compared with published results. Substantial heterogeneity between trials was also evident, increasing uncertainty. The TEC Assessment concluded that the 5 meta-analyses, sampling from a similar collection of published trials and two unpublished ones, highlight biases and difficulty ascertaining clinically meaningful patient-level improvement compared with placebo. Although accumulating evidence would be expected to increase certainty about whether a clinically important treatment benefit exists, the current studies do not provide convincing evidence that the net health outcome is improved with IA hyaluronan over placebo.

The 2016 literature review did not identify any additional RCTs evaluating IA hyaluronan for the treatment of knee OA. However, a number of systematic reviews and meta-analyses were published after the 2014 TEC Assessment.^{10,11,12,13,14,15,16,17} Only four of them reported pooled analyses synthesizing results of RCTs that compared IA hyaluronan with placebo, and reported the outcome, pain.^10,11,12,14 Three of the 4 new meta-analyses concluded that IA hyaluronan injections for knee OA provided a clinically meaningful reduction in pain compared with placebo.^11,12,14 The other meta-analysis (Jevsevar et al.¹⁰) concluded that evidence from trials at low risk of bias (e.g., double-blind, sham-controlled) did not demonstrate a clinically meaningful benefit of IA hyaluronan. (Two of the meta-analyses concluding benefit of IA hyaluronan also limited analysis to trials at low risk of bias.) Only the review by Jevsevar et al. reported a minimally clinically important difference with treatment (-0.29). As noted in the 2014 TEC Assessment, "... for a standardized mean difference, a minimally important difference of -0.37 is sometimes cited..."⁴

In addition to the meta-analyses of trials directly comparing IA hyaluronan and placebo, a network meta-analysis by Bannuru et al. addressed this comparison indirectly.¹⁷ The investigators included 137 studies examining a number of treatments for knee OA: IA hyaluronan, intra-articular steroids, acetaminophen, diclofenac, ibuprofen, naproxen and celecoxib.¹⁷ Although none of the included trials compared IA hyaluronan directly with oral placebo, the authors concluded that if IA hyaluronan were to be compared to oral placebo, it would be the most effective of the agents considered in the review. For example, when indirect comparisons were made with oral placebo, the standardized mean difference for pain relief reported at (or nearest) 3 months with IA hyaluronan was 0.63 (95% credible interval (CrI), 0.39 to 0.88)^a and with ibuprofen was 0.44 (95% CrI, 0.25 to 0.63). The estimated pain relief effect for IA hyaluronan compared with oral placebo was nearly double that for IA hyaluronan compared with a sham procedure.

However, conclusions that can be drawn from the newer meta-analyses are limited by potential biases with included trials. The presence of publication bias has been documented in the IA hyaluronan literature.⁵ Likewise, a small trial bias has been noted with effect estimates from smaller trials ( < 100 participants) almost three-fold that of large trials. These observations are consistent with positive results from a small trial having a higher probability of being reported than a small negative one (or possibly a small negative trial having even been completed). In summary, the results from the 2015 – 2016 meta-analyses, which do not include any new RCTs, do not alter conclusions of the 2014 TEC Assessment on the impact of IA hyaluronan on health outcomes in patients with knee OA.

Osteoarthritis of Joints Other Than the Knee
Ankle Osteoarthritis
Evidence was examined from RCTs and systematic reviews that have been published. A 2015 Cochrane review by Witteveen et al. addressed IA hyaluronan and other conservative treatments for ankle OA.¹⁸ The investigators identified 6 RCTs, 3 of which were double-blind and compared IA hyaluronan with placebo. The other trials were single-blind. Two of them compared IA hyaluronan to another treatment (exercise in 1 study and botulinum toxin in the other study) and the sixth study compared different doses of hyaluronan. Five of the 6 studies included patients with unilateral ankle pain. Sample sizes at the time of randomization ranged from 17 to 75, and length of follow-up ranged from 3 to 12 months. The authors pooled findings only for 2 of the 3 studies comparing IA hyaluronan and placebo. Meta-analyses of efficacy outcomes (pain, function) did not find statistically significant benefit of IA hyaluronan over placebo, with the exception of the outcome Ankle Osteoarthritis Scale (AOS) total score at 6 months. For the AOS outcome, the pooled effect size was -12.53 (95% confidence interval [CI], -23.84 to -1.22) in favor of IA hyaluronan; however, the evidence for this analysis was rated as low due to the limitation in study design (i.e., unclear risk of bias) and "…imprecision of result (low number of participants)." No serious adverse events were reported and no patient withdrew from the study due to an adverse event.

A 2011 review of IA hyaluronan for ankle OA by Migliore et al. considered both RCTs and observational studies.¹⁹ The authors identified 3 small RCTs with a total of 75 patients, and 4 case series. In 2 of the RCTs, IA hyaluronan was compared with placebo injection and the third RCT compared IA hyaluronan with exercise therapy. The authors were unable to do a meta-analysis due to the limited number of studies and study heterogeneity.

Foot Osteoarthritis
There is a very limited amount of evidence on IA hyaluronan injections in the foot. Munteanu et al. reported on an RCT of a single IA hyaluronan injection in 151 patients with first metatarsophalangeal joint OA.²⁰ At the 1-, 3- and 6-month follow-up, there were no significant differences between the IA hyaluronan and placebo groups on the Foot Health Status Questionnaire.

Thumb Osteoarthritis
Two systematic reviews evaluated IA hyaluronan, as well as corticosteroid injections, for treating thumb OA. The 2016 review by Kroon et al. identified 3 studies comparing HA and placebo and 6 comparing IA hyaluronan and corticosteroids.²¹ Findings of the HA studies were not pooled. Unlike the Kroon et al. review, the 2015 systematic review by Trellu et al. included only RCTs and pooled study data.²² Six trials (total N = 428 patients) were included in the meta-analyses; 169 patients were treated with HA, 147 with corticosteroids and 74 with placebo. In pooled analyses of studies comparing IA hyaluronan and placebo (74 patients in each arm), there was no significant between-group difference in pain at week 12 (standardized response mean [SRM], -0.95; 95% CI, -3.87 to 1.97); however, functional capacity at week 12 was significantly better after IA hyaluronan than placebo (SRM = -1.14; 95% CI, -1.69 to -0.60). When IA hyaluronan and corticosteroids were compared, there was no significant difference in pain, functional capacity or pulp pinch force at 12 weeks. At 24 weeks, findings were mixed. There was no significant between IA hyaluronan and corticosteroids in functional capacity, HA was superior on pulp pinch force status (SRM = -1.66; 95% CI, -0.75 to -2.57) and corticosteroids were superior on pain (SRM = 1.44; 95% CI, 0.14 to 2.74).

Hip Osteoarthritis
A 2015 systematic review by Lieberman et al. included RCTs and observational studies with a minimum of 10 patients evaluating IA hyaluronan for treatment of pain associated with hip OA.²³ A total of 23 studies were identified, 6 of which were RCTs. The studies evaluated 11 different formulations of HA. Duration of follow-up varied; 19 studies followed patients for 6 months or less, 3 studies had between 6 months and 1 year of follow-up and only 1 study followed patients for more than 1 year. The primary efficacy outcome was change from baseline in pain measured by a visual analog scale (VAS). The authors did not report the number of points on the VAS but presumably this differed across studies and the authors appeared to standardize results on a 10-point VAS. A pooled analysis of data from all studies found a statistically significantly lower pain score at follow-up compared to baseline. Mean change was -1.97 points on a VAS (95% CI, -2.83 to -1.12). In a pooled analysis of the 6 RCTs, there was a significantly greater decrease in pain with IA hyaluronan compared with a control intervention (-0.27 points on a VAS; 95% CI, -0.43 to -0.11). Although statistically significant, a between-group difference of 0.27 points on a VAS may not be clinically meaningful.

Shoulder Osteoarthritis
A 2014 systematic review by Colen et al. identified RCTs, controlled observational studies and case series evaluating IA hyaluronan for treatment of glenohumeral OA in adult patients.²⁴ Eight studies met the eligibility criteria; 2 were RCTs, 5 were prospective case series and 1 was a retrospective case control study. Due to heterogeneity among studies and the small number of controlled studies, authors did not pool study findings on the efficacy of IA hyaluronan for treating shoulder OA compared with placebo or an alternative intervention. The RCTs are described next.

Blaine et al. (2008) was an industry-sponsored trial of 660 patients with persistent shoulder pain due to glenohumeral joint OA, rotator cuff tear and/or adhesive capsulitis that compared 3 weekly injections versus 5 weekly injections of sodium hyaluronate (Hyalgan) versus 5 weekly injections of saline.²⁵ Approximately 60% of patients had OA, although most of those with OA also had rotator cuff disorders or capsulitis. Sixty-nine percent (n = 456) of the patients had a follow-up visit at 26 weeks. There was no significant difference among groups in the primary outcome measure, shoulder pain with movement at 13 weeks. Analysis of predefined, stratified subgroups revealed no significant differences in reported pain at 13 weeks but a statistically significant decrease of 7.5 mm and 7.8 mm (on a 100-mm VAS) in reported pain in both treatment groups at 26 weeks compared with placebo among patients with OA. In those without OA, there was no significant improvement with either regimen. Of note, this appears to be an as-treated analysis of the OA subgroup data, and the difference may not be clinically meaningful.

In 2013, Kwon et al. published findings from a multicenter, randomized, double-blind, placebo-controlled trial of IA hyaluronan in 300 patients with glenohumeral OA.²⁶ Intention-to-treat analysis found similar improvement from baseline in 100-mm VAS for pain (19.88 mm for IA hyaluronan, 16.29 mm for sham treatment) and in the Outcome Measures in Rheumatoid Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) high responder rate (40.8% for IA hyaluronan, 34.9% for sham) at 26 weeks. In a subset of IA hyaluronan patients, there was a statistically significant difference of 4.0 mm in VAS score and 8.37% on the OMERACT-OARSI. However, the clinical significance of these differences is uncertain.

Spine Osteoarthritis
The data are limited to small pilot studies and case series.

Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed in Table 1. 

Table 1. Summary of Key Trials

NCT: National clinical trial. 

Clinical Input Received From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests, input was received from five academic medical centers (six reviewers) and three physician specialty societies while this policy was under review in 2011. Most reviewers agreed that IA hyaluronan of the knee was medically necessary. In addition, those providing input supported an interval of 6 months for repeat injections. In response to a question about total number of treatment courses, there was no consensus.

Practice Guidelines and Position Statements
American Medical Society for Sport Medicine
The 2016 scientific statement from the American Medical Society for Sport Medicine (AMSSM) recommended IA hyaluronan for "appropriate" patients with knee osteoarthritis (OA) based on high-quality evidence.¹² Patient selection criteria include individuals age 60 and older with Kellgren-Lawrence grade 2 – 3 OA. The society also "suggests" IA hyaluronan for patients under age 60 with knee OA based on moderate quality indirect evidence.  

American Academy of Orthopaedic Surgeons
The 2013 guideline of the American Academy of Orthopaedic Surgeons (AAOS) on treatment of OA of the knee states that it cannot recommend using IA hyaluronan for patients with symptomatic knee OA.⁶ This is a strong recommendation, meaning that the quality of the supporting evidence is high. This recommendation was based on a meta-analysis of 3 high-strength and 11 moderate-strength studies that showed that the overall effect was less than 0.5 minimally important different units, indicating a low likelihood that an appreciable number of patients achieved clinically important benefits. AAOS states that practitioners should follow a strong recommendation unless a clear and compelling rationale for an alternative approach is present. This replaces a 2008 guideline in which a recommendation could not be made for IA hyaluronan due to inconclusive evidence.

The 2009 (reaffirmed 2014) AAOS Clinical Practice Guideline on glenohumeral joint osteoarthritis²⁷ includes a weak grade C recommendation that: "The use of injectable viscosupplementation is an option when treating patients with glenohumeral [shoulder] osteoarthritis." Grade C recommendations are based on poor-quality evidence. In this instance, the recommendation is based on a single case series of 30 patients with OA of the glenohumeral joint who received 3 weekly IA injections of Synvisc.²⁸ At 1, 3 and 6 months, clinically significant improvements were seen in pain, function and quality-of-life measures.  

American College of Rheumatology
The American College of Rheumatology (ACR) published updated guidelines in 2012 that addressed OA of the hand, hip and knee.²⁹ A conditional recommendation was given for IA hyaluronan to treat OA of the knee. ACR recommends not using IA hyaluronan for OA of the hand. For OA of the hip, ACR explicitly made no recommendation regarding treatment with IA hyaluronan due to the lack of RCTs. 

Osteoarthritis Research Society International

The 2014 Osteoarthritis Research Society International guidelines, developed by consensus after review of existing guidelines and systematic reviews, gave an "uncertain" recommendation for the use of IA hyaluronan for knee OA and a recommendation of "not appropriate" for multiple-joint OA.³⁰ 

National Institute for Health and Care Excellence
The 2014 guidelines by the National Institute for Health and Care Excellence³¹ state: "Do not offer intra-articular hyaluronan injections for the management of osteoarthritis."  

U.S. Preventive Services Task Force Recommendations
Not applicable 

References

1. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Intra-Articular Hyaluronan Injections for Treatment of Osteoarthritis of the Knee. TEC Assessments 1998;Volume 13, Tab 17.
2. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Special Report: intra-articular hyaluronan for osteoarthritis of the knee. TEC Assessments. 2004;Volume 19, Tab 17.
3. Samson DJ, Grant MD, Ratko TA, et al. Treatment of primary and secondary osteoarthritis of the knee. AHRQ Publication No. 07-E012. September 2007; http://www.ncbi.nlm.nih.gov/books/NBK38385/. Accessed March 11, 2016.
4. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Intra-articular hyaluronic acid for osteoarthritis of the knee. TEC Assessments. 2014;Volume 29, Tab 6.
5. Rutjes AW, Juni P, da Costa BR, et al. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med. Aug 7 2012;157(3):180-191. PMID 22868835
6. American Academy of Orthopaedic Surgeons. Treatment of osteoarthritis of the knee. 2013; http://www.aaos.org/research/guidelines/TreatmentofOsteoarthritisoftheKneeGuideline.pdf. Accessed March 11, 2016.
7. Bannuru RR, Natov NS, Dasi UR, et al. Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis--meta-analysis. Osteoarthritis Cartilage. Jun 2011;19(6):611-619. PMID 21443958
8. Colen S, van den Bekerom MP, Mulier M, et al. Hyaluronic acid in the treatment of knee osteoarthritis: a systematic review and meta-analysis with emphasis on the efficacy of different products. BioDrugs. Aug 1 2012;26(4):257-268. PMID 22734561
9. Miller LE, Block JE. US-approved intra-articular hyaluronic acid injections are safe and effective in patients with knee osteoarthritis: systematic review and meta-analysis of randomized, saline-controlled trials. Clin Med Insights Arthritis Musculoskelet Disord. 2013;6:57-63. PMID 24027421
10. Jevsevar D, Donnelly P, Brown GA, et al. Viscosupplementation for Osteoarthritis of the Knee: A Systematic Review of the Evidence. J Bone Joint Surg Am. Dec 16 2015;97(24):2047-2060. PMID 26677239
11. Richette P, Chevalier X, Ea HK, et al. Hyaluronan for knee osteoarthritis: an updated meta-analysis of trials with low risk of bias. RMD Open. 2015;1(1):e000071. PMID 26509069
12. Trojian TH, Concoff AL, Joy SM, et al. AMSSM scientific statement concerning viscosupplementation injections for knee osteoarthritis: importance for individual patient outcomes. Br J Sports Med. Jan 2016;50(2):84-92. PMID 26729890
13. Ammar TY, Pereira TA, Mistura SL, et al. Viscosupplementation for treating knee osteoarthrosis: review of the literature. Rev Bras Ortop. Sep-Oct 2015;50(5):489-494. PMID 26535192
14. Strand V, McIntyre LF, Beach WR, et al. Safety and efficacy of US-approved viscosupplements for knee osteoarthritis: a systematic review and meta-analysis of randomized, saline-controlled trials. J Pain Res. 2015;8:217-228. PMID 26005358
15. Wang F, He X. Intra-articular hyaluronic acid and corticosteroids in the treatment of knee osteoarthritis: A meta-analysis. Exp Ther Med. Feb 2015;9(2):493-500. PMID 25574222
16. Newberry SJ, Fitzgerald JD, Maglione MA, et al. Systematic Review for Effectiveness of Hyaluronic Acid in the Treatment of Severe Degenerative Joint Disease (DJD) of the Knee. Rockville MD2015.
17. Bannuru RR, Schmid CH, Kent DM, et al. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. Jan 6 2015;162(1):46-54. PMID 25560713 
18. Witteveen AG, Hofstad CJ, Kerkhoffs GM. Hyaluronic acid and other conservative treatment options for osteoarthritis of the ankle. Cochrane Database Syst Rev. 2015;10:CD010643. PMID 26475434
19. Migliore A, Giovannangeli F, Bizzi E, et al. Viscosupplementation in the management of ankle osteoarthritis: a review. Arch Orthop Trauma Surg. Jan 2011;131(1):139-147. PMID 20697901
20. Munteanu SE, Zammit GV, Menz HB, et al. Effectiveness of intra-articular hyaluronan (Synvisc, hylan G-F 20) for the treatment of first metatarsophalangeal joint osteoarthritis: a randomised placebo-controlled trial. Ann Rheum Dis. Oct 2011;70(10):1838-1841. PMID 21791454
21. Kroon FP, Rubio R, Schoones JW, et al. Intra-Articular Therapies in the Treatment of Hand Osteoarthritis: A Systematic Literature Review. Drugs Aging. Feb 2016;33(2):119-133. PMID 26650235
22. Trellu S, Dadoun S, Berenbaum F, et al. Intra-articular injections in thumb osteoarthritis: A systematic review and meta-analysis of randomized controlled trials. Joint Bone Spine. Oct 2015;82(5):315-319. PMID 25776442
23. Lieberman JR, Engstrom SM, Solovyova O, et al. Is intra-articular hyaluronic acid effective in treating osteoarthritis of the hip joint? J Arthroplasty. Mar 2015;30(3):507-511. PMID 25542833
24. Colen S, Geervliet P, Haverkamp D, et al. Intra-articular infiltration therapy for patients with glenohumeral osteoarthritis: A systematic review of the literature. Int J Shoulder Surg. Oct 2014;8(4):114-121. PMID 25538430
25. 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 2008;90(5):970-979. PMID 18451387
26. Kwon YW, Eisenberg G, Zuckerman JD. Sodium hyaluronate for the treatment of chronic shoulder pain associated with glenohumeral osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled trial. J Shoulder Elbow Surg. Jan 16 2013;22(5):584-594. PMID 23333168
27. American Academy of Orthopaedic Surgeons. The treatment of glenohumeral joint osteoarthritis: guideline and evidence report. 2009; http://www.aaos.org/research/guidelines/gloguideline.pdf. Accessed March 11, 2016.
28. Silverstein E, Leger R, Shea KP. The use of intra-articular hylan G-F 20 in the treatment of symptomatic osteoarthritis of the shoulder: a preliminary study. Am J Sports Med. Jun 2007;35(6):979-985. PMID 17395958
29. Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). Apr 2012;64(4):465-474. PMID 22563589
30. McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. Mar 2014;22(3):363-388. PMID 24462672
31. National Institute for Health and Clinical Excellence (NICE). CG177 Osteoarthritis: Care and management in adults. 2014; http://publications.nice.org.uk/osteoarthritis-cg177/recommendations#pharmacological-management. Accessed March 11, 2016. 

Coding Section 

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

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines. 

"Current Procedural Terminology © American Medical Association. All Rights Reserved"  

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