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

Clinical Policy Number: 00.02.08

Effective Date: October 1, 2014

Initial Review Date: April 16, 2014

Most Recent Review Date: July 20, 2016

Next Review Date: July 2017

Related policies:

CP# 14.02.08 Prolotherapy

ABOUT THIS POLICY: Keystone First has developed clinical policies to assist with making coverage determinations. Keystone First’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 peer-reviewed 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 Keystone First 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. Keystone First’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. Keystone First’s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, Keystone First will update its clinical policies as necessary. Keystone First’s clinical policies are not guarantees of payment.

Coverage policy

Keystone First 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;

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.

Policy contains:

Hyaluronic acid.

Viscosupplementation.

Osteoarthritis of the knee.

Chondromalacia.

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Criteria for Medical Necessity

(Criteria A,B,C,D,E and F must be met)

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:

­ Lateral epidcondyltis (“tennis elbow”), as the condition is frequently self-limiting.

­ Glenohumeral joint arthritis.

­ Any tendinitis diagnosis.

­ 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), and 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 2020. 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 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.

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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

Keystone First 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 22, 2016. 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

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.

Keystone First 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).

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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

An RCT (Askari 2016) inclusive of 140 patients with knee OA randomized subjects to receive intra-articular 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 three months for knee joint OA, while corticosteroids needed to be injected

every two 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 Content, Methods, Recommendations

Askari (2016)

Hyaluronic acid compared with

corticosteroid injections for the

treatment of osteoarthritis of the

knee: a randomized control trail.

Key points:

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).

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Citation Content, Methods, Recommendations

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:

­ HA 3 months.

­ Corticosteroids 2 months.

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.

Key points:

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.

Chandrasekaran (2016)

Symposium: evidence for the use

of intra-articular cortisone or

hyaluronic acid injection in the

hip.

Key points:

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--

meta-analysis.

Key points:

Systematic review evaluated treatments for primary knee OA:- Aug 2014.

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.

Bannuru (2014)

Relative efficacy of hyaluronic

acid in comparison with NSAIDs

for knee osteoarthritis: a

systematic review and meta-

analysis.

Key points:

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

Samson (2014) Key points:

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Citation Content, Methods, Recommendations

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

meta-analyses; 21 RCTs of glucosamine/chondroitin, 16 synthesized among 6

meta-analyses; and 23 articles on arthroscopy.

Viscosupplementation trials generally report positive effects on pain and

function 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.

Schmajuk (2014)

Using Medicare Data to

Understand Low-Value Health

Care: The Case of Intra-articular

Hyaluronic Acid Injections.

Key points:

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.

Key points:

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 intra-articular

hyaluronic acid for ankle

osteoarthritis treatment: a

systematic review and meta-

analysis.

Key points:

Ankle osteoarthritis:

RCTs (4); CCTs (1) or prospective cohort (4): vs. saline, exercise or

arthroscopy 345 subjects total; 1995 – 2012;

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.

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Citation Content, Methods, Recommendations

Hayes (2013)

Viscosupplementation for

chondromalacia.

Key points:

Chondromalacia.

Searches — July 2013;

Mostly animal studies; very limited human clinical data;

No products are specifically FDA-approved for chondromalacia.

Hayes (2013)

Preoperative

viscosupplementation for the

treatment of knee conditions.

Key points:

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;

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.

Krogh (2013)

Comparative effectiveness of

injection therapies in lateral

epicondylitis: a systematic review

and network meta-analysis of

randomized controlled trials.

Key points:

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.

Key points:

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.

Key points:

Knee osteoarthritis.

Available evidence of high quality; .

Intra-articular injection in patients for whom non-pharmacological treatments or

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Citation Content, Methods, Recommendations

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.

Trigkilidas (2013)

The effectiveness of hyaluronic

acid intra-articular injections in

managing osteoarthritic knee

pain.

Key points:

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.

American College of

Rheumatology (2012)

Recommendations for the use of

nonpharmacologic and

pharmacologic therapies in

osteoarthritis of the hand, hip, and

knee.

Key points:

Osteoarthritis: does not cover HA.

Rutjes (2012)

Viscosupplementation for

osteoarthritis of the knee: a

systematic review and meta-

analysis.

Key points:

Osteoarthritis of knee.

RCTs or quasi — Jan 2012.

89 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.

Bannuru (2011)

Therapeutic trajectory following

intra-articular hyaluronic acid

injection in knee osteoarthritis--

meta-analysis.

Key points:

Therapeutic trajectory after injection for knee osteoarthritis.

RCTs — Mar 2010.

54 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.

Coombes (2010)

Efficacy and safety of

corticosteroid injections and other

injections for management of

tendinopathy.

Key points:

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 2010.

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Citation Content, Methods, Recommendations

41 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.

Hayes (2009)

Sodium hyaluronate for

osteoarthritis.

Key points:

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”:

­ Single course of treatment for OA of knee with goal of improving

symptoms and function.

­ 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.

Key points:

Osteoarthritis of the hip — insufficient evidence.

Glossary

Chondromalacia — Also known as patello-femoral pain syndrome or chondromalacia patellae. A painful repetitive

trauma- or overuse-related condition, in which joint cartilage softens and breaks down, becoming unable to

perform its usual functions of cushioning and protecting opposing bones within the joint. While any joint cartilage

may be involved, the most common site is the underside of the patella (kneecap) and the individuals most

commonly affected are athletes and the elderly.

Glenohumeral — Related to the shoulder joint, which is a multiaxial synovial ball and socket joint. Involves

articulation between the glenoid fossa of the scapula (shoulder blade) and the head of the humerus (upper arm

bone). Due to the very limited interface of the humerus and scapula, it is the most mobile joint of the human body.

Lateral epicondylitis — Also known as “tennis elbow.” An idiopathic and generally self-limiting condition in which

the outer part of the elbow becomes tender. It is usually due to over-exertion, a sudden forceful pull, or incorrect

tennis technique, any of which can result in micro-or macroscopic tears to tendons in the joint.

Non-steroidal anti-inflammatory drugs (NSAIDs) — A class of drugs with both analgesic and anti-inflammatory

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effects. They include ibuprofen (Advil®) and naproxen (Aleve®), and are available over the counter in the United

States. They are used for acute and chronic conditions involving pain and inflammation, such as osteoarthritis,

rheumatoid arthritis, low back pain, headache, and toothache. Since gastrointestinal side effects are prominent,

they should be avoided by people with dyspepsia or other existing gastrointestinal conditions, such as diarrhea or

bleeding.

Prolotherapy — Also known as proliferation or regenerative injection therapies. Involves injecting a non-

pharmacologic or inactive but irritant substance (e.g., dextrose or glycerin) into a joint or surrounding tissues to

promote healing and resolve symptoms.

Synovial joint — Bony intersection in which the ends of the articulating bones are separated by a joint cavity and

enclosed in a joint capsule containing synovial fluid.

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. 2013.

Hayes Inc., Hayes Medical Technology Report. Preoperative viscosupplementation for the treatment of knee

conditions. Lansdale, Pa. Hayes Inc.; 2013.

Hayes Inc., Hayes Medical Technology Report. Sodium hyaluronate for osteoarthritis. Lansdale, Pa. Hayes Inc.;

2009.

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 2012.

Hayes Inc., Hayes Medical Technology Report. Viscosupplementation for chondromalacia. Lansdale, Pa. Hayes Inc.;

2013.

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):465-474.

Michigan Quality Improvement Consortium. Medical management of adults with osteoarthritis. Southfield (MI);

Michigan Quality Improvement Consortium. 2013.

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. 2013.

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 Evidencebased

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Practice Center under Contract No. 290-02-0026). AHRQ Publication No. 07-E012. Rockville, MD: Agency for

Healthcare Research and Quality. 2007.

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;5:442.

Bannuru RR, Natov NS, Dasi UR, Schmid CH, McAlindon TE. Therapeutic trajectory following intra-articular

hyaluronic acid injection in knee osteoarthritis--meta-analysis. Osteoarthritis and cartilage / OARS, Osteoarthritis

Research Society. 2011;19(6):611-619.

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):593-599.

Brander VA, Stadler TS. Functional improvement with hylan G-F 20 in patients with knee osteoarthritis. The

Physician and sportsmedicine. 2009;37(3):38-48.

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):951-960.

Cianflocco AJ. Viscosupplementation in patients with osteoarthritis of the knee. Postgraduate medicine.

2013;125(1):97-105.

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. 20

2010;376(9754):1751-1767.

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); 2005.

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):465-474.

Iannitti T, Lodi D, Palmieri B. Intra-articular injections for the treatment of osteoarthritis: focus on the clinical use

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of hyaluronic acid. Drugs in R&D. 2011;11(1):13-27.

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):1435-1446.

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;6:57-63.

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. 7 2012;157(3):180-191.

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):1702-1704.

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):545-551.

Clinical trials

Searched ClinicalTrials.gov on June 28, 2016 using terms: Open Studies | hyaluronic acid. Nineteen studies found; 5

relevant.

NuCel, LLC. An Investigation of ReNu™ Knee Injection in Patients With Osteoarthritis. ClinicalTrials.gov Web site.

http://clinicaltrials.gov/show/NCT02318511. Published December 9, 2014. Updated November 2015. Accessed

June 28, 2016.

University of California, San Francisco. To Look at the Characteristics of Synovial Fluid and Cartilage Matrix in

Osteoarthritic Knee After Hyaluronic Acid Injection. ClinicalTrials.gov Web site.

http://clinicaltrials.gov/show/NCT01895959. Published July 5, 2013. Updated September 2015. Accessed June 28,

2016.

New York University School of Medicine. Effectiveness Trial for Evaluating IAHA for PFPS (PFPS). ClinicalTrials.gov

Web site. http://clinicaltrials.gov/show/NCT02318511. Published February 15, 2013. Updated April 2016. Accessed

June 28, 2016.

Laval University. Daily Activity and Gait Analysis After Viscosupplement Injection Among Hip Osteoarthritis

Patients. ClinicalTrials.gov Web site. http://clinicaltrials.gov/show/NCT02086474. Published March 7, 2014.

Updated March 2016. Accessed June 28, 2016.

ProCore Ltd. A Phase I, Prospective, Randomized, Open-label, Active-Controlled Clinical Trial for Safety Evaluation

13

of Intra-articular Injection of RegenoGel-SP for the Treatment of Moderate to Severe Osteoarthritis.

ClinicalTrials.gov Web site. https://ClinicalTrials.gov/show/NCT02188771. Published July 10, 2014. Updated July

2014. Accessed June 28, 2016.

Centers for Medicare & Medicaid Services (CMS) national coverage determinations (NCDs).

No NCDs found at this time.

Local coverage determinations (LCDs)

Hyaluronan acid therapies for osteoarthritis of the knee (L32237). Available at: http://www.cms.gov/medicare-

coverage-database/details/lcd-

details.aspx?LCDId=32237&ContrId=314&ver=24&ContrVer=1&SearchType=Advanced&CoverageSelection=Both&

NCSelection=NCD&PolicyType=Final&s=All&KeyWord=Hyaluronan&KeyWordLookUp=Title&KeyWordSearchType=

Exact&kq=true&bc=IAAAABAAAAAAAA%3d%3d&. Accessed June 28, 2015.

Intra-articular Injections of hyaluronan (L30149). Available at: http://www.cms.gov/medicare-coverage-

database/details/lcd-

details.aspx?LCDId=30149&ContrId=143&ver=39&ContrVer=1&SearchType=Advanced&CoverageSelection=Both&

NCSelection=NCD&PolicyType=Final&s=All&KeyWord=Hyaluronan&KeyWordLookUp=Title&KeyWordSearchType=

Exact&kq=true&bc=IAAAABAAAAAAAA%3d%3d&. Accessed June 28, 2015.

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.

CPT Code Description Comment

20610 Arthrocentesis, aspiration and/or injection; major joint or bursa (eg, shoulder,

hip, knee, subacromial bursa); without ultrasound guidance

20611 Arthrocentesis, aspiration and/or injection; major joint or bursa (eg, shoulder,

hip, knee, subacromial bursa); without ultrasound guidance

ICD-10 Code Description Comment

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

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ICD-10 Code Description Comment

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 Description Comment

J7321 Hyaluronan or derivative:(Hylgan or Supartz) for intra-articular injection.

J7323 Hyaluronan or derivative: (Euflexxa)for intra-articular injection.

J7324 Hyaluronan or derivative: (Orthovisc) for intra-articular injection.

J7325 Hyaluronan or derivative: (ynvisc or SynviscOne) for intra-articular injection.

J7326 Hyaluronan or derivative: (Gel-One) for intra-articular injection.

APPENDIX A

PerformRx criteria:

Field Name Field Description

Prior Authorization Group HYALURONIC ACID DERIVATIVES.

Drug(s) EUFLEXXA is PREFERRED agent.

Gel-One

Hyalgan

Monovisc

Orthovisc

Supartz

Covered Uses *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).

Exclusion Criteria None.

Required Medical Information See other criteria.

Age Restrictions None.

Prescriber Restrictions None.

Coverage Duration If all of the criteria is met, the request will be approved for one complete course

15

Field Name Field Description

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.

Other Criteria 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.

Revision/Review Date: 4/2015