Clinical Policy Title: Intra-articular hyaluronic acid injection for osteoarthritis

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1 Clinical Policy Title: Intra-articular hyaluronic acid injection for osteoarthritis Clinical Policy Number: Effective Date: October 1, 2014 Initial Review Date: April 16, 2014 Most Recent Review Date: July 20, 2017 Next Review Date: July 2018 Related policies: Policy contains: Hyaluronic acid. Viscosupplementation. Osteoarthritis of the knee. Chondromalacia. CP# CP# CP# CP# Aquatic therapy Major joint replacement (hip and knee) Spinal surgeries Prolotherapy ABOUT THIS POLICY: AmeriHealth Caritas Louisiana has developed clinical policies to assist with making coverage determinations. AmeriHealth Caritas Louisiana s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peerreviewed professional literature. These clinical policies, along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by AmeriHealth Caritas Louisiana when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. AmeriHealth Caritas Louisiana s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. AmeriHealth Caritas Louisiana s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, AmeriHealth Caritas Louisiana will update its clinical policies as necessary. AmeriHealth Caritas Louisiana s clinical policies are not guarantees of payment. Coverage policy AmeriHealth Caritas Louisiana considers the use of intra-articular injection with hyaluronic acid (HA) to be clinically proven and, therefore, medically necessary when all of the following criteria are met: Criteria for Medical Necessity (Criteria A,B,C,D,E and F must be met) A. Documented symptomatic mild to moderate knee osteoarthritis. B. Patient reports pain interfering with functional activities, such as ambulation or prolonged standing. C. One of the following criteria: 1. Conservative therapy (oral medications) over the past four months has not resulted in functional improvement after at least three months; 2. Patient cannot tolerate other treatments (e.g., non-steroidal anti-inflammatory drugs [NSAIDs]) because of adverse effects; 3. Other therapy is contraindicated because of other medical problems; 1

2 Criteria for Medical Necessity (Criteria A,B,C,D,E and F must be met) 4. Steroid injection therapy was administered within the prior two months and aspiration for effusion was unsuccessful, per affected knee; or 5. There is a medical reason for not being able to utilize steroid injections. D. The pain cannot be attributed to other forms of joint disease. E. A single course of treatment is given as described in the package insert of each product F. Specific prior authorization criteria in Appendix A are met. Limitations: All other uses of intra-articular injection with hyaluronic acid are not medically necessary. Other uses include, but are not limited to: o Lateral epidcondyltis ( tennis elbow ), as the condition is frequently self-limiting. o Glenohumeral joint arthritis. o Any tendinitis diagnosis. o Chondromalacia. Coverage of specific pharmaceuticals and/or treatments is subject to prior authorization by plan criteria. Prior authorization criteria for the pharmaceuticals listed in this policy is set forth in Appendix A. Alternative covered services: Simple analgesics. Nonsteroidal anti-inflammatory drugs (NSAIDs). Corticosteroid injections. Background Osteoarthritis (OA) is a chronic and progressive disease resulting from failure of joint cartilage repair after breakdown or wear, accompanied by changes in synovial fluid, pain, and joint movement limitations. OA is the most common type of arthritis, particularly in the elderly, and is associated with high rates of disability. Aging populations and the risk factor of obesity contribute to increasing prevalence in developed countries U.S. (United States) prevalence is expected to nearly double by The most commonly affected joints include cervical and lumbosacral spine, hip, knee, and first metatarsal-phalangeal (base of thumb); in other words, joints ill-suited by evolution for prolonged weight bearing or other bipedal locomotion uses, while others (wrist and elbow) are usually spared. OA is diagnosed by structural abnormalities (loss of joint space) on imaging studies and associated symptoms (activity-related joint pain and disability). Pharmacologic treatment includes acetaminophen, NSAIDs, and COX-2 inhibitors. Other options are intra-articular injections with corticosteroids or hyaluronic acid. Optimal therapy tends to the idiosyncratic and is achieved by trial and error for each 2

3 patient. When medical therapy fails and patients find unacceptable reduction in quality of life, knee or hip total arthroplasty (arthroscopic debridement and lavage) may be considered. Sodium hyaluronate HA is a viscoelastic substance occurring naturally in synovial fluid and extracellular matrices of many tissues, including cartilage and skin. It plays a role in joint lubrication, protection, and cartilage maintenance. Commercially available preparations, administered as intra-articular injections, are used to relieve pain, improve synovial fluid quantity or quality, and to modify disease progression in osteoarthritis and other joint diseases. Other medical uses of HA include: Dry, scaly skin, such as that caused by atopic dermatitis or eczema, in a prescription skin lotion containing sodium hyaluronate as its active ingredient. As a tumor marker for prostate and breast cancer. In some cancers, HA levels correlate well with malignancy and poor prognosis. It may also be used to monitor the progression of the disease. Postoperatively to induce tissue healing, notably after cataract surgery. Current models of wound healing propose the larger polymers of HA appear in the early stages of healing to physically make room for white blood cells, which mediate the immune response. In the synthesis of biological scaffolds for wound-healing applications. These scaffolds typically have proteins such as fibronectin attached to the HA to facilitate cell migration into the wound. This application is particularly important for individuals with diabetes suffering from chronic wounds, such as foot or leg ulcers. Searches: AmeriHealth Caritas Louisiana searched PubMed and the databases of: UK National Health Services Centre for Reviews and Dissemination. Agency for Healthcare Research and Quality Guideline Clearinghouse and evidence-based practice centers. The Centers for Medicare & Medicaid Services. We conducted searches on June 9, Searched terms were hyaluronic acid, injection therapies and osteoarthritis. We included: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. Findings 3

4 The evidence supporting the efficacy and safety of HA intra-articular injection for improving pain and function in osteoarthritis and other musculoskeletal conditions has recently improved. Prior to 2010, most reviewers cited insufficient evidence; since then, reviewers generally agree on HA s effectiveness. However, experts continue to cite small study sizes and the need for larger randomized controlled trials (RCTs) to support selection criteria and cost-utility. This information, along with the safety profiles and relative costs of included treatments, will be helpful for individualized patient care decisions. AmeriHealth Caritas Louisiana identified one systematic review from the Blue Cross Blue Shield Technology Evaluation Center for the Agency for Healthcare Research and Quality (Samson 2014); one analysis of Medicare utilization data (Schmajuk 2014); and one clinical practice guideline from the American Academy of Orthopedic Surgeons (AAOS 2013). Results of the two systematic reviews reflect some continued uncertainty regarding the effectiveness of intra-articular HA for treatment of knee osteoarthritis. Indirect comparisons suggest some improvement in pain and function relative to other available treatments, but comparisons to placebo have yielded conflicting results. An analysis of Medicare utilization data found frequent use of intra-articular HA among Medicare beneficiaries despite its higher cost, uncertain effectiveness, lack of optimal patient selection criteria, and variations in recommendations from evidence-based guidelines. Therefore, it is reasonable to offer intra-articular HA for individuals who have failed to respond adequately to conservative nonpharmacologic therapy, simple analgesics and anti-inflammatories. Policy updates A systematic review evaluated the effectiveness of a course of 3 or 5 weekly intra-articular injections of Hyalgan to treat knee OA pain in 2168 study participants. The pooled estimate for relief from baseline pain was (SE, 5.46; 95% confidence interval [CI], to -17.4) with a 3-week course of Hyalgan and (SE, 5.25; 95% CI, to -18.7) with a 5-week course of Hyalgan. Findings from the metaanalysis indicate relief of knee OA pain with a 3-week course of Hyalgan is similar to that with a 5-week course of Hyalgan (P=.916). The pooled estimate for relief from baseline pain with a 3-week course of other HA products was (SE, 4.98; 95% CI, to -16.6), also indicating pain relief with a 3-week course of Hyalgan is similar to that with a 3-week course of other HA products (P=.696). In sum, there was no statistical difference between reduction in knee OA pain with a 3-week course of Hyalgan compared with reduction in knee OA pain with a 5-week course of Hyalgan or a 3-week course of other HA products. An RCT (Askari 2016) inclusive of 140 patients with knee OA randomized subjects to receive intraarticular injection of either HA or corticosteroid. The mean age of the patients in the corticosteroid group was 57 ± 1.9 years and in the HA group was 58.5 ± 8.3 years. Pain and stiffness did not improve in either of the groups at any time points after the intervention (p > 0.05). However, a different pain scale suggested that symptoms improved after 3 months in both corticosteroid and HA groups, and daily activity improved in both groups (p < 0.05). The most important difference between the two intervention groups was the duration of effectiveness: HA could be administered intra-articularly every 4

5 3 months for knee joint OA, while corticosteroids needed to be injected every 2 months to maintain symptom control. Strand (2016) evaluated an injectable viscoelastic hydrogel composed of a cross-linked hyaluronate (Gel- 200 ) in a 13-week trial and demonstrated statistically significant improvements in patients treated with a single injection of Gel-200 compared with a saline control. Improvements in pain score were evident as early as 3 weeks following injection with more than 40 percent improvement from baseline. Adverse events were not significantly different between the intervention group and saline controls. No unanticipated treatment-related serious adverse events were reported. A systematic review (Chandrasekaran 2016) of 72 RCTs assessed the use of corticosteroid, HA and platelet rich plasma (PRP) in the non-operative management of OA and femoroacetabular impingement. The authors affirmed the efficacy of diagnostic intra-articular hip injections, finding them sensitive and specific for differentiating between intra-articular, extra-articular and spinal causes of hip symptoms. With regard to therapy, corticosteroids were more effective than HA and PRP in alleviating pain from hip OA. A higher dose of corticosteroids produced a longer benefit. Summary of clinical evidence: Citation Stitik (2017) Effectiveness of 3 weekly injections compared with 5 weekly injections of intraarticular sodium hyaluronate on pain relief of knee osteoarthritis or 3 weekly injections of other hyaluronan products Askari (2016) Content, Methods, Recommendations Systematic review investigated whether the number of HA injections in a sodium hyaluronate course of therapy alters effectiveness in reducing knee OA pain. Twenty-four studies were identified, comprising 2168 study participants in 30 treated cohorts. The pooled estimate for relief from baseline pain was (SE, 5.46; 95% confidence interval [CI], to -17.4) with a 3-week course of Hyalgan and (SE, 5.25; 95% CI, to -18.7) with a 5-week course of Hyalgan. Findings from the meta-analysis indicate relief of knee OA pain with a 3-week course of Hyalgan is similar to that with a 5-week course of Hyalgan (P=.916). The pooled estimate for relief from baseline pain with a 3-week course of other HA products was (SE, 4.98; 95% CI, to -16.6), also indicating pain relief with a 3-week course of Hyalgan is similar to that with a 3-week course of other HA products (P=.696). These findings demonstrate that comparable knee OA pain relief is achieved with a 3- week course of Hyalgan and the 2 control groups. Hyaluronic acid compared with corticosteroid injections for the treatment of osteoarthritis of the knee: a randomized control trail. An RCT inclusive of 140 patients with knee OA. Randomized subjects to receive intra-articular injection of either HA or corticosteroid. Mean age in the corticosteroid group was 57 ± 1.9 years and in the HA group was 58.5 ± 8.3 years. Pain and stiffness did not improve in either of the groups at any time points after the intervention (p > 0.05). A different pain scale suggested that symptoms improved after 3 months in both corticosteroid and HA groups (p < 0.05). The most important difference between the two intervention groups was the duration of effectiveness: 5

6 Citation Strand (2016) Evidence for safety of retreatment with a single intra-articular injection of Gel-200 for treatment of osteoarthritis of the knee from the double-blind pivotal and open-label retreatment clinical trials. Chandrasekaran (2016) Content, Methods, Recommendations o HA 3 months. o Corticosteroids 2 months. An RCT evaluated Gel-200 in a 13-week trial. Statistically significant improvements were noted compared with a saline control. Improvements in pain score were evident as early as 3 weeks. Adverse events were not significantly different between the intervention group and saline controls. No unanticipated treatment-related serious adverse events were reported. Symposium: evidence for the use of intra-articular cortisone or hyaluronic acid injection in the hip.. A systematic review of 72 RCTs Assessed the use of corticosteroid, HA and platelet rich plasma (PRP). Affirmed the efficacy of diagnostic intra-articular hip injections. Corticosteroids were more effective than HA and PRP in alleviating pain from hip OA. A higher dose of corticosteroids produced a longer benefit. Bannuru (2015) Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis--metaanalysis Bannuru (2014) Relative efficacy of hyaluronic acid in comparison with NSAIDs for knee osteoarthritis: a systematic review and metaanalysis Samson (2014) Systematic review evaluated treatments for primary knee OA:- Aug Network meta-analysis of 137 studies (33,243 subjects). HA most efficacious treatment: effect size 0.63 (95% credible interval [CrI], 0.39 to 0.88) for pain control; acetaminophen least efficacious: effect size 0.18 (CrI, 0.04 to 0.33). For function, all interventions except IA corticosteroids superior to oral placebo. For stiffness, NS differences among treatments. Limitations: Lack of long-term data, inadequate reporting of safety data, possible publication bias, and few head-to-head comparisons. HA v. NSAIDs for knee osteoarthritis: RCTs, - Feb 2013; 5 trials (712 subjects); No significant differences at 4 and 12 weeks; No safety concerns from review but limited by short follow-up Treatment of Primary and Secondary Osteoarthritis of the Knee. Systematic review of outcomes of three treatments for osteoarthritis (OA) of the knee: intra-articular viscosupplementation; oral glucosamine, chondroitin or the combination; and arthroscopic lavage or debridement. Included 42 RCTs of viscosupplementation, all but one synthesized among six metaanalyses; 21 RCTs of glucosamine/chondroitin, 16 synthesized among 6 metaanalyses; and 23 articles on arthroscopy. Viscosupplementation trials generally report positive effects on pain and function 6

7 Citation Schmajuk (2014) Content, Methods, Recommendations scores compared to placebo The evidence on clinical benefit is uncertain, due to variable trial quality, potential publication bias, and unclear clinical significance of the changes reported. The best available evidence does not clearly demonstrate clinical benefit. Using Medicare Data to Understand Low-Value Health Care: The Case of Intra-articular Hyaluronic Acid Injections. Study reviewed 1,161,924 injections with intra-articular hyaluronic acid among 423,669 patients by 12,761 physicians or other clinicians. Most formulations of hyaluronic acid consisted of 3 injections given 1 week apart. The average cost per injection paid by Medicare was $179 for the drug and $69 for the injection. An analysis by regions showed that rates of intra-articular hyaluronic acid injections were clustered (p <.001). Higher rates of injection of intra-articular hyaluronic acid were associated with higher numbers of physicians, surgeons, and rheumatologists. AAOS (2013) Clinical practice guideline on the treatment of osteoarthritis of the knee Knee osteoarthritis Strong recommendation against using IAHA for patients with symptomatic knee osteoarthritis. Based on 14 studies (3 high-strength studies and 11 moderate-strength studies) indicating a low likelihood that IAHA provides minimum clinically important improvement to patients. Chang (2013) Effectiveness of intraarticular hyaluronic acid for ankle osteoarthritis treatment: a systematic review and meta-analysis Hayes (2013) Viscosupplementation for chondromalacia Hayes (2013) Ankle osteoarthritis: RCTs (4); CCTs (1) or prospective cohort (4): vs. saline, exercise or arthroscopy 345 subjects total; ; Significant reduction in pain versus before treatment; Molecular weight of preparation not associated with magnitude of pain relief but increases in total doses and active ingredients may be. Increased injection volume may be associated with reduced effect; Extremely high molecular weight preparations frequently caused early post-injection pain; Multiple doses and appropriate injection volume recommended. Chondromalacia: Searches July 2013; Mostly animal studies; very limited human clinical data; No products are specifically FDA-approved for chondromalacia. Preoperative viscosupplementation for the treatment of knee conditions Preoperative viscosupplementation for knee conditions: Products used in included studies: Orthovisc; Synvisc; Adant; Viscoseal; Suplasyn; Synochrom; 6 RCTs, 1 CCT: anterior cruciate ligament tear or rupture; osteoarthritis; meniscal tear; 30 to 80 subjects/study; FU, 6 weeks to 2 years; 7

8 Citation Krogh (2013) Content, Methods, Recommendations Heterogeneity precluded meta-analysis but several studies reported benefits in pain reduction, range of motion/function, cartilage volume; No or few significant side effects reported. Comparative effectiveness of injection therapies in lateral epicondylitis: a systematic review and network metaanalysis of randomized controlled trials Injection therapies for lateral epicondylitis: 17 RCTs (1381 subjects);overall low risk of bias; 8 treatments assessed: glucocorticoids (10 trials); botulinum toxin (4); autologous blood (3); PRP (2); HA (1) and prolotherapy; Beyond 8 weeks: glucocorticoids no more effective than placebo; botulinum toxin had marginal benefit with temporary paralysis of finger extension; Superior to placebo: autologous blood; plasma; hyaluronic acid; and prolotherapy but all trials subject to bias; Additional research is needed. Miller (2013) Systematic Review and Meta-Analysis of Randomized, Saline- Controlled Trials Knee osteoarthritis: Full-text English-language RCTs 2013: Hyalgan; Synvisc; Supartz/Artzal; Orthovisc; Gel-One; Euflexxa were most commonly studied; 29 trials (4866 subjects); most of moderate quality although with substantial heterogeneity; Significant improvements in knee pain and function at 4 to 26 weeks; no differences in safety outcomes (inconsistently reported). Pichon-Riviere (2013) Intra-articular use of hyaluronic acid in the treatment of knee osteoarthritis. Trigkilidas (2013) The effectiveness of hyaluronic acid intra-articular injections in managing osteoarthritic knee pain American College of Rheumatology (2012) Recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Knee osteoarthritis. Available evidence of high quality;. Intra-articular injection in patients for whom non-pharmacological treatments or simple analgesics were ineffective slightly reduces pain and improves mobility vs placebo or intra-articuar corticosteroids in 3 to 6 month evaluation period. Evidence lacking for: benefit to repeated doses or impact on joint replacement. Most guidelines and insurers cover for knees which have not responded to other treatments. Osteoarthritic knee pain. 14 RCTS. HA has modest effect on early-to-moderate knee OA. Effect peaks at 6 to 8 weeks and by 6 months is doubtful. Osteoarthritis: does not cover HA. 8

9 Citation Rutjes (2012) Viscosupplementation for osteoarthritis of the knee: a systematic review and metaanalysis Bannuru (2011) Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis--metaanalysis Coombes (2010) Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy Hayes (2009) Content, Methods, Recommendations Osteoarthritis of knee. RCTs or quasi Jan moderate quality trials (12,667 subjects). Viscosupplementation has minimal or no benefit to patients with symptomatic OA of the knee. Serious adverse effects argue against use. Therapeutic trajectory after injection for knee osteoarthritis. RCTs Mar studies (7545 subjects). HA better than placebo, peaking at 8 weeks, residual detectable effect at 24 weeks. HA modestly effective for knee OA pain over six months from injection. Cost-utility analyses are needed. Corticosteroid and other injections ( prolotherapy, glycosaminoglycan polysulfate, proteinase, HA, PRP, botulinum toxin, NSAID) for tendinopathy (lateral or medial epicondyle, rotator cuff, Achilles,or patellar): RCTs without language restriction Mar studies (2672 subjects). Corticosteroids: improvements on all outcomes in short-term treatment; better than prolotherapy or no treatment for all tendinopathies. Non-corticosteroid injection: some improvements for some tendinopathies for varying periods. Challenged long-term use of corticosteroid injections as less effective than more conservative therapies. Additional large high-quality studies supporting subgroup analyses needed. Sodium hyaluronate for osteoarthritis Osteoarthritis. Moderate to strong evidence that intra-articular injection reduces pain and improves. function in patients who did not respond to or cannot tolerate conservative therapy. Magnitude of effect similar to corticosteroids. HA may be an option when steroids fail. Hayes rating B : o Single course of treatment for OA of knee with goal of improving symptoms and function. o Conflicting results from mixed boy of evidence (efficacy and safety) for hip OA. Fernandez-Lopez (2005) Efficacy and safety of hyaluronic acid in the treatment of osteoarthritis of the hip Osteoarthritis of the hip insufficient evidence. 9

10 References Professional society guidelines/other: American Academy of Orthopedic Surgeons (AAOS). Clinical practice guideline on the treatment of osteoarthritis of the knee. Second edition. Rosemont (IL): American Academy of Orthopedic Surgeons Hayes Inc., Hayes Medical Technology Report. Preoperative viscosupplementation for the treatment of knee conditions. Lansdale, Pa. Hayes Inc.; Hayes Inc., Hayes Medical Technology Report. Sodium hyaluronate for osteoarthritis. Lansdale, Pa. Hayes Inc.; Hayes Inc., Hayes Medical Technology Report. Synovisc (hylang-f 20) (Genzyme Corp) for arthritis of the ankle. Lansdale, Pa. Hayes Inc.; 2009; reviewed 2011; archived as outdated July Hayes Inc., Hayes Medical Technology Report. Viscosupplementation for chondromalacia. Lansdale, Pa. Hayes Inc.; 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 & research. 2012;64(4): Michigan Quality Improvement Consortium. Medical management of adults with osteoarthritis. Southfield (MI); Michigan Quality Improvement Consortium Pichon-Riviere A, Augustovski F, Garcia Marti S, et al. Intra-articular use of hyaluronic acid in the treatment of knee osteoarthritis. Institute for Clinical Effectiveness and Health Policy (IECS) Report No.305. Buenos Aires; IECS Samson DJ, Grant MD, Ratko TA, Bonnell CJ, Ziegler KM, Aronson N. Treatment of Primary and Secondary Osteoarthritis of the Knee. Evidence Report/Technology Assessment No. 157 (Prepared by Blue Cross and Blue Shield Association Technology Evaluation Center Evidence based Practice Center under Contract No ). AHRQ Publication No. 07-E012. Rockville, MD: Agency for Healthcare Research and Quality Peer-reviewed references: Askari A, Gholami T, NaghiZadeh MM, Farjam M, Kouhpayeh SA, Shahabfard Z. Hyaluronic acid compared with corticosteroid injections for the treatment of osteoarthritis of the knee: a randomized control trail. SpringerPlus. 2016;5:

11 Bannuru RR, Natov NS, Dasi UR, Schmid CH, McAlindon TE. Therapeutic trajectory following intraarticular hyaluronic acid injection in knee osteoarthritis--meta-analysis. Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 2011;19(6): Bannuru RR, Vaysbrot EE, Sullivan MC, McAlindon TE. Relative efficacy of hyaluronic acid in comparison with NSAIDs for knee osteoarthritis: a systematic review and meta-analysis. Seminars in arthritis and rheumatism. 2014;43(5): Brander VA, Stadler TS. Functional improvement with hylan G-F 20 in patients with knee osteoarthritis. The Physician and sportsmedicine. 2009;37(3): Chang KV, Hsiao MY, Chen WS, Wang TG, Chien KL. Effectiveness of intra-articular hyaluronic acid for ankle osteoarthritis treatment: a systematic review and meta-analysis. Archives of physical medicine and rehabilitation. 2013;94(5): Cianflocco AJ. Viscosupplementation in patients with osteoarthritis of the knee. Postgraduate medicine. 2013;125(1): Chandrasekaran S, Lodhia P, Suarez-Ahedo C, Vemula SP, Martin TJ, Domb BG. Symposium: evidence for the use of intra-articular cortisone or hyaluronic acid injection in the hip. Journal of Hip Preservation Surgery. 2016;3(1):5-15. Coombes BK, Bisset L, Vicenzino B. Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials. Lancet ;376(9754): Fernandez-Lopez JC, Ruano-Ravina A. Efficacy and safety of hyaluronic acid in the treatment of osteoarthritis of the hip. Santiago de Campostela: Galician Agency for Health Technology Assessment (AVALIA-T); Henrotin Y, Hauzeur JP, Bruel P, Appelboom T. Intra-articular use of a medical device composed of hyaluronic acid and chondroitin sulfate (Structovial CS): effects on clinical, ultrasonographic and biological parameters. BMC research notes. 2012;5:407. 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 & research. 2012;64(4): Iannitti T, Lodi D, Palmieri B. Intra-articular injections for the treatment of osteoarthritis: focus on the clinical use of hyaluronic acid. Drugs in R&D. 2011;11(1):

12 Krogh TP, Bartels EM, Ellingsen T, et al. Comparative effectiveness of injection therapies in lateral epicondylitis: a systematic review and network meta-analysis of randomized controlled trials. The American journal of sports medicine. 2013;41(6): 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. Clinical medicine insights. Arthritis and musculoskeletal disorders. 2013;6: Rutjes AW, Juni P, da Costa BR, Trelle S, Nuesch E, Reichenbach S. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Annals of internal medicine ;157(3): Schmajuk G, Bozic KJ, Yazdany J. Using Medicare Data to Understand Low-Value Health Care: The Case of Intra-articular Hyaluronic Acid Injections. JAMA Intern Med. 2014;174(10): Stitik TP, Issac SM, Modi S, Nasir S, Kulinets I. Effectiveness of 3 weekly injections compared with 5 weekly injections of intra-articular sodium hyaluronate on pain relief of knee osteoarthritis or 3 weekly injections of other hyaluronan products: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2017;98(5): Strand V, Lim S, Takamura J. Evidence for safety of retreatment with a single intra-articular injection of Gel-200 for treatment of osteoarthritis of the knee from the double-blind pivotal and open-label retreatment clinical trials. BMC Musculoskeletal Disorders. 2016;17:240. Trigkilidas D, Anand A. The effectiveness of hyaluronic acid intra-articular injections in managing osteoarthritic knee pain. Annals of the Royal College of Surgeons of England. 2013;95(8): CMS National Coverage Determinations (NCDs): No NCDs identified as of the writing of this policy. Local coverage determinations (LCDs): No LCDs identified as of the writing of this policy. Commonly submitted codes Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill accordingly. 12

13 CPT Code Description Comments 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); without ultrasound guidance ICD-10 Code Description Comments 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 HCPCS Level II Code J7321 J7323 J7324 J7325 J7326 Description Hyaluronan or derivative:(hylgan or Supartz) for intra-articular injection. Hyaluronan or derivative: (Euflexxa)for intra-articular injection. Hyaluronan or derivative: (Orthovisc) for intra-articular injection. Hyaluronan or derivative: (ynvisc or SynviscOne) for intra-articular injection. Hyaluronan or derivative: (Gel-One) for intra-articular injection. Comments APPENDIX A PerformRx criteria Field Name Prior Authorization Group Drug(s) Covered Uses Field Description HYALURONIC ACID DERIVATIVES EUFLEXXA is PREFERRED agent Gel-One Hyalgan Monovisc Orthovisc Supartz Synvisc Synvisc One Any other newly mar keted Hyaluronic Acid derivative *Medically accepted indications are defined using the following sources: the Food and Drug Administration (FDA), Micromedex, American Hospital Formulary Service (AHFS), United States Pharmacopeia Drug Information for the Healthcare Professional (USP DI), or the Drug Package Insert (PPI). 13

14 Exclusion Criteria Required Medical Information Age Restrictions Prescriber Restrictions Coverage Duration Other Criteria Revision/Review Date: 3/2017 None See other criteria None None If all of the criteria is met, the request will be approved for one complete course of treatment (based on the FDA labeled dose of the drug requested). If all of the criteria is not met, the request is referred to a Medical Director for medical necessity review. Initial Authorization: A diagnosis of Osteoarthritis (OA)/Degenerative joint disease (DJD) of the knee. There is documentation (in claim history or provider statement) that the patient recently (over the past 4 months) has had adequate trials on simple analgesics (acetaminophen containing products or topical capsaicin cream) & NSAIDS (including two different prescription strength NSAIDS) on a continuous basis for 3 months without success or has a medical reason (intolerance, hypersensitivity, contraindication, etc.) for not being able to utilize simple analgesic products and NSAIDS. Documentation has been provided that a steroid injection has been tried and failed, per affected knee or patient has a medical reason for not being able to utilize steroid injections. If the request is for any other product other than Euflexxa, the patient has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not using Euflexxa to treat their medical condition. Reauthorization: At least 6 months have elapsed since the previous course of HAD therapy for the treated knee(s). Documentation was submitted that the patient had a response to the treated knee (s) that lasted for > 6 months to previous HAD therapy, as documented by at least ONE of the following: Decreased joint pain or stiffness, improved knee range of motion, decrease in midpatellar knee circumference in millimeters, or synovial effusion absent or volume decreased. Documentation was submitted that the patient has a return of symptoms of osteoarthritis, and has been retreated with NSAIDS and simple analgesics (acetaminophen containing products or topical capsaicin cream) without success, or has a medical reason (intolerance, hypersensitivity, contraindication, etc) for not being able to utilize simple analgesic products and NSAIDS. If the request is for any other product other than Euflexxa, the patient has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not using Euflexxa to treat their medical condition. If all of the criteria is not met, the request is referred to a Medical Director for medical necessity review. 14