Medical Policy

Policy Num:       07.001.039
Policy Name:     Meniscal Allografts and Other Meniscal Implants

Policy ID:          [ 07.001.039]  [Ac / B / M+ / P+]  [7.01.15]

Last Review:     May 06, 2024
Next Review:     May 20, 2025
 

Related Policies:

07.001.156 - Autologous Chondrocyte Implantation for Focal Articular Cartilage Lesions
07.001.043 - Autografts and Allografts in the Treatment of Focal Articular Cartilage Lesions

Meniscal Allografts and Other Meniscal Implants

Summary

Meniscal allografts and other meniscal implants (eg, collagen) are intended to improve symptoms and reduce joint degeneration in patients who have had a total or partial meniscus resection.

For individuals who are undergoing partial meniscectomy who receive meniscal allograft transplantation, the evidence includes systematic reviews of mostly case series and a randomized controlled trial. The relevant outcomes are symptoms, functional outcomes, and quality of life. The systematic reviews concluded that most studies have shown statistically significant improvements in pain and function following the procedure. The benefits have also been shown to have a long-term effect (>10 years). Reviews have also reported acceptable complication and failure rates. There remains no evidence that meniscal allograft transplantation can delay or prevent the development of knee osteoarthritis. A limitation of the evidence is its reliance primarily on case series. Because the single randomized controlled trial, which enrolled a very small number of patients, pooled data from randomized and nonrandomized groups, results cannot be interpreted in a meaningful way. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who are undergoing partial meniscectomy and concomitant repair of malalignment, focal chondral defects, and/or ligamentous insufficiency who receive meniscal allograft transplantation, the evidence includes a systematic review of case series as well as case series published after the systematic review. The relevant outcomes are symptoms, functional outcomes, and quality of life. The systematic review concluded that pain and function improved following the procedure. One of the series published after the review showed that patients with more severe cartilage damage experienced favorable outcomes similar to patients with less cartilage damage. Another series published subsequently reported an overall 9.7-year survival of the implant. A limitation of the evidence is its reliance primarily on case series. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who are undergoing partial meniscectomy who receive collagen meniscal implants (CMIs), the evidence includes 2 systematic reviews primarily of case series. Relevant outcomes are symptoms, functional outcomes, and quality of life. The reviews reported overall positive results with the CMI, but the quality of the selected studies (RCTs, observational studies) was low. Radiologic evaluations have shown reductions in the size of the implant in a large portion of patients. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome

Additional Information

Not applicable.

Objective

The objective of this evidence review is to determine the net health outcome when meniscal allografts are used to treat patients with disabling knee pain following meniscectomy who are too young for total knee arthroplasty.

Policy Statements

Meniscal allograft transplantation may be considered medically necessary in patients who have had a prior meniscectomy and have symptoms related to the affected side when all of the following criteria are met:

• Adult patients should be too young to be considered an appropriate candidate for total knee arthroplasty or other reconstructive knee surgery (eg, <55 years)
• Disabling knee pain with activity that is refractory to conservative treatment
• Absence or near absence (>50%) of the meniscus, established by imaging or prior surgery
• Documented minimal to absent diffuse degenerative changes in the surrounding articular cartilage (eg, Outerbridge grade II or less, <50% joint space narrowing)
• Normal knee biomechanics or alignment and stability achieved concurrently with meniscal transplantation.

Meniscal allograft transplantation may be considered medically necessary when performed in combination, either concurrently or sequentially, with treatment of focal articular cartilage lesions using any of the following procedures:

• autologous chondrocyte implantation, or
• osteochondral allografting, or
• osteochondral autografting.

Use of other meniscal implants incorporating materials such as collagen are considered investigational.

Policy Guidelines

Patients should exhibit symptoms of persistent disabling knee pain that has not adequately responded to physical therapy and analgesic medications. Uncorrected misalignment and instability of the joint are contraindications. Therefore, additional procedures, such as repair of ligaments or tendons or creation of an osteotomy for realignment of the joint, may be performed at the same time.

Severe obesity (eg, body mass index >35 kg/m²) may affect outcomes due to the increased stress on weight-bearing surfaces of the joint. Meniscal allograft transplantation is typically recommended for young active patients who are too young for total knee arthroplasty.

Coding

Please see the Codes table for details.

Benefit Application

BlueCard/National Account Issues

State or federal mandates (eg, Federal Employee Program) may dictate that certain U.S. Food and Drug Administration-approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity.

Plans may consider requiring prior approval or preauthorization for meniscal allograft. 

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

Background

Meniscal Cartilage Damage

Meniscal cartilage is an integral structural component of the human knee, functioning to absorb shocks and providing load sharing, joint stability, congruity, proprioception, and lubrication and nutrition of the cartilage surfaces. Total and partial meniscectomy frequently result in degenerative osteoarthritis. The integrity of the menisci is particularly important in knees in which the anterior cruciate ligament has been damaged. In these situations, the menisci act as secondary stabilizers of anteroposterior and varus-valgus translation.

Treatment

Meniscal allograft transplantation (MAT) is considered a salvage procedure, reserved for patients with disabling knee pain following meniscectomy who are considered too young to undergo total knee arthroplasty or in patients who require a total or near total meniscectomy for irreparable tears. As a result, the population intended to receive these transplants is relatively limited. Using a large database of privately insured non-Medicare patients, Cvetanovich et al (2015) estimated an annual incidence of MAT in the U. S. of 0.24 per 100000.^1, It is not expected that clinical trials will be conducted to compare meniscal allografts with other orthopedic procedures, although trials comparing allograft transplant with medical therapy are possible.

There are three general groups of patients who have been treated with MAT:

• young patients with a history of meniscectomy who have symptoms of pain and discomfort associated with early osteoarthritis that is localized to the meniscus-deficient compartment
• patients undergoing anterior cruciate ligament reconstruction in whom a concomitant meniscal transplant is intended to provide increased stability
• young athletes with few symptoms in whom the allograft transplantation is intended to deter the development of osteoarthritis. Due to the risks associated with this surgical procedure, prophylactic treatment for this purpose is not frequently recommended.

Issues under study include techniques for processing and storing the grafts, proper sizing of the grafts, and appropriate surgical techniques. The four primary ways of processing and storing allografts are fresh viable, fresh frozen, cryopreserved, and lyophilized. Fresh viable implants, harvested under sterile conditions, are less frequently used because the grafts must be used within a couple of days to maintain viability. Alternatively, the harvested meniscus can be fresh frozen for storage until needed. Cryopreservation freezes the graft in glycerol, which aids in preserving the cell membrane integrity and donor fibrochondrocyte viability. CryoLife is a commercial supplier of such grafts. Donor tissues may also be dehydrated (freeze-dried or lyophilized), permitting storage at room temperature. Lyophilized grafts are prone to reduced tensile strength, shrinkage, poor rehydration, posttransplantation joint effusion, and synovitis; they are no longer used in the clinical setting. Several secondary sterilization techniques may be used, with gamma irradiation the most common. The dose of radiation considered effective has been shown to change the mechanical structure of the allograft; therefore, nonirradiated grafts from screened donors are most frequently used. In a survey conducted by the International Meniscus Reconstruction Experts Forum, when surgeons were asked about allograft preference, 68% preferred fresh frozen nonirradiated allografts, with 14% responding fresh viable allografts.^2,

There are several techniques for MAT; most are arthroscopically assisted or all-arthroscopic. Broadly, the techniques are either all-suture fixation or bone fixation. Within the bone fixation category, the surgeon may use either bone plugs or a bone bridge. Types of bone bridges include keyhole, trough, dove-tail, and bridge-in-slot. The technique used depends on laterality and the need for concomitant procedures. Patients with malalignment, focal chondral defects, and/or ligamentous insufficiency may need concomitant procedures (osteotomy, cartilage restoration, and/or ligament reconstruction, respectively).^3,

Tissue engineering that grows new replacement host tissue is also being investigated. For example, the Collagen Meniscus Implant (Ivy Sports Medicine, formerly the ReGen Collagen Scaffold by ReGen Biologics), is a resorbable collagen matrix composed primarily of type I collagen from bovine Achilles tendons. The implant is provided in a semilunar shape and trimmed to size for suturing to the remaining meniscal rim. The implant provides an absorbable collagen scaffold that is replaced by the patient's soft tissue; it is not intended to replace normal body structure. Because it requires a meniscal rim for attachment, it is intended to fill meniscus defects after a partial meniscectomy. Other scaffold materials and cell-seeding techniques are being investigated. Nonabsorbable and nonporous synthetic implants for total meniscus replacement are in development. One total meniscus replacement that is in early phase clinical testing is NUsurface® (Active Implants); it is composed of a polyethylene reinforced polycarbonate urethane.

Outcome Measures

The outcomes of this treatment (ie, pain, functional status) are subjective, patient-reported outcomes that are prone to placebo effects. On the other hand, the natural history of a severely damaged meniscus is predictable, with progressive joint damage, pain, and loss of function.

Regulatory Status

Collagen Meniscus Implants

In 2008, the ReGen Collagen Scaffold was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process. The FDA determined that this device was substantially equivalent to existing absorbable surgical mesh devices. The ReGen Collagen Scaffold (also known as MenaFlex^TM CMI) was the only collagen meniscus implant with the FDA clearance at that time. Amid controversy about this 510(k) clearance decision, the FDA reviewed its decision. In October 2010, the FDA rescinded the approval, stating that MenaFlex^TM is intended for different purposes and is technologically dissimilar from the predicate devices identified in the approval process. The manufacturer appealed the rescission and won its appeal in 2014. The product, now called CMIÒ, is manufactured by Ivy Sports Medicine. CMIÒ is the only FDA-approved collagen meniscus product currently on the market.

FDA product code: OLC.

Rationale

This evidence review was created in December 1995 with searches using the PubMed database. The most recent literature update was performed through February 20, 2024.

Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life, and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, 2 domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent 1 or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Population Reference No. 1

Meniscal Allograft Transplantation

Clinical Context and Therapy Purpose

The purpose of meniscal allograft transplantation (MAT) is to provide a treatment option that is an alternative to or an improvement on existing therapies, such as partial meniscectomy without MAT, in patients who are undergoing partial meniscectomy.

The following PICO was used to select literature to inform this review.

P opulations

The relevant population of interest is individuals who are undergoing partial meniscectomy.

Interventions

The therapy being considered is MAT. Meniscal allografts and other meniscal implants (eg, collagen) are intended to improve symptoms and reduce joint degeneration in patients who have had a total or partial meniscus resection.

Comparators

Comparators of interest include partial meniscectomy without MAT.

Partial meniscectomy without MAT is performed by an orthopedic surgeon in an inpatient clinical setting.

Outcomes

The general outcomes of interest are symptoms, functional outcomes, and quality of life.

Table 1. Outcomes of Interest for Individuals Undergoing Partial Meniscectomy

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

Systematic Reviews

Several systematic reviews of available case series have reported reductions in pain and improvements in function at mid-term follow-up, with failure rates at the time of follow-up ranging from 7% to 35% ( Table 2). Elattar et al (2011) published a large systematic review with a total of 1136 allografts.^4, Twelve different clinical scoring systems were described, which generally showed reductions in pain and improvements in function. Hergan et al (2011) conducted a systematic review of the literature to evaluate the characteristics of patients, graft survival, and clinical outcomes.^5, The analysis found that patients with Outerbridge scores of II or less in any area had significantly improved posttreatment Lysholm Knee Score (LKS) and Tegner Activity Scale (TAS) scores, whereas patients with Outerbridge grade III or more in any area (not repaired) did not. Studies that analyzed patients undergoing concomitant procedures did not detect a difference between subgroups compared with MAT alone. Functional outcomes were considered generally good where reported. Rosso et al (2015) published a systematic review evaluating 55 studies ( N=1623 patients).^6, Data from 37 studies were included in demographic and outcome analyses. Collectively, these systematic reviews, which are based primarily on level IV evidence, summarize the short- to medium-term outcomes of MAT ( Table 2).

Table 2. Summary of Systematic Reviews of Meniscal Allograft Transplantation

LKS: Lysholm Knee Score; MAT: meniscal allograft transplantation; VAS: visual analog scale.a Data from 37 of the 55 studies in the systematic review.

Randomized Controlled Trials

Smith et al (2018) reported on the results of a small RCT that randomized 21 patients with a symptomatic meniscal deficient knee to MAT (n=10) or personalized physical therapy (n=11).^7, Another 15 patients who were screened for the RCT decided instead to choose their treatment (referred to as the preference group), receiving MAT (n=6) or personalized physical therapy (n=9). The Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee score, LKS score, and complications were collected at baseline, 4 and 8 months, and 1 year after the interventions. Trialists reported pooled results from the RCT and preference group, with statistically significant differences in favor of the MAT group for KOOS composite score (mean difference, 12; p=0.03) and KOOS subscales of pain (mean difference, 15; p=0.02) and activities of daily living (mean difference, 18; p=0.005). However, pooling data from the RCT and preference group precluded a meaningful interpretation of data.

Case Series

The characteristics and results of several case series with longer-term follow-up are provided in Tables 3 and 4. Verdonk et al (2005) published a large case series with long-term follow-up from 95% of their first 105 fresh cultured (viable) meniscal allografts.^8, The indication for transplantation was moderate-to-severe pain in patients who had undergone previous total meniscectomy, not old enough to be considered for a knee joint replacement, and with good alignment of the lower limb and a stable joint (some were corrected concomitantly). In the study by Hommen et al (2007), concomitant procedures were performed in 75% of the patients, including anterior cruciate ligament reconstruction or revision (n=10), high tibial osteotomy (n=2), and lateral retinaculum release (n=3).^9,

At a mean follow-up of 16 years, van der Wal et al (2009)^10, reported graft survival decreased to 52.5%, while most failures in the study by Vundelinckx et al (2010)^11, occurred approximately 10 years postoperatively. That said, at an average of 105 months of follow-up, the 34 remaining patients assessed in the Vundelinckx et al (2010) study showed significant reductions in pain and improvements in function relative to preoperative levels. Radiographic evidence reported by van der Wal et al (2009) also showed a slight or moderate increase in osteoarthritis in 42% of patients (1 or 2 points) and no increase in the other 58%. Of 15 patients with follow-up radiographs in the Hommen et al (2007) study, 10 (67%) had joint space narrowing, and 12 (80%) had a progression of the Fairbank degenerative joint disease score in the transplanted tibiofemoral compartment.

Table 3. Summary of Case Series Characteristics for Meniscal Allograft Transplantation

FU: follow-up; MAT: meniscal allograft transplantation.

Table 4. Summary of Case Series Outcomes for Meniscal Allograft Transplantation

Base: baseline; FU: follow-up; KOOS: Knee Injury and Osteoarthritis Outcome Score; LKS: Lysholm Knee Score; VAS: visual analog scale.

Section Summary: Meniscal Allograft Transplantation

Evidence for the use of MAT in patients with disabling knee pain and a prior meniscectomy consists of systematic reviews of a large number of case series and an RCT. The reviews have found that MAT is associated with reductions in pain and improvements in function. Longer-term studies have indicated that these improvements are maintained in a substantial percentage of patients, up to 10 years and beyond. Because the results of a single RCT, which enrolled a very small number of patients, pooled data from randomized and nonrandomized groups, results cannot be interpreted in a meaningful way. Adverse events, such as graft failure and the need for additional procedures, occur frequently. The strength of the evidence, including accurate estimates of the magnitude of benefit and the complication rates, are limited by the type of data available (case series and systematic reviews of these case series) as well as the heterogeneity in surgical techniques and patient characteristics across the studies.

For individuals who are undergoing partial meniscectomy who receive  meniscal allograft transplantation  (MAT), the evidence includes systematic reviews of mostly case series and an RCT. The relevant outcomes are symptoms, functional outcomes, and QOL. The systematic reviews concluded that most studies have shown statistically significant improvements in pain and function following the procedure. The benefits have also been shown to have a long-term effect (>10 years). Reviews have also reported acceptable complication and failure rates. There remains no evidence that MAT can delay or prevent the development of knee osteoarthritis. A limitation of the evidence is its reliance primarily on case series. Because of the single RCT, which enrolled a very small number of patients, pooled data from randomized and nonrandomized groups, results cannot be interpreted in a meaningful way. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 2

Meniscal Allograft Transplantation Plus Articular Cartilage Repair

Clinical Context and Therapy Purpose

The purpose of MAT is to provide a treatment option that is an alternative to or an improvement on existing therapies, such as partial meniscectomy without MAT, in patients who are undergoing partial meniscectomy and repair of malalignment, focal chondral defects and/or ligamentous insufficiency.

The following PICO was used to select literature to inform this review.

P opulations

The relevant population of interest is individuals who are undergoing partial meniscectomy and repair of malalignment, focal chondral defects and/or ligamentous insufficiency.

Interventions

The therapy being considered is MAT. Patients with malalignment, focal chondral defects, and/or ligamentous insufficiency may require additional surgery combined with MAT. When MAT is combined with osteotomy or articular cartilage repair in a single procedure, MAT should be performed first.

Comparators

Comparators of interest include partial meniscectomy without MAT.

Outcomes

The general outcomes of interest are symptoms, functional outcomes, and quality of life.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

Systematic Reviews

Harris et al (2011) published a systematic review of MAT plus cartilage repair or restoration ( Table 5).^12, Patients underwent MAT with autologous chondrocyte implantation (n=73), osteochondral allograft (n=20), osteochondral autograft (n=17), or microfracture (n=3). All studies showed improvement in clinical outcomes at final follow-up compared with the preoperative condition. Outcomes were similar to historical outcomes, extracted from mid-term and long-term follow-up studies, of procedures performed in isolation. Additional surgeries are common (nearly 50%) after MAT plus cartilage repair or restoration procedures.

Table 5. Summary of Systematic Reviews for Meniscal Allograft Transplantation Plus Articular Cartilage Repair

MAT: meniscal allograft transplantation.

The largest and longest study to report on MAT in patients with significant (grade III and IV) chondral damage is that by Stone et al (2010) who reported mean allograft survival of 9.9 years ( Table 6 ).^13, Other prospective studies have reported on graft survival and functional outcomes when MAT has been combined with articular cartilage repair.^14,15,

Case Series

The following studies were published subsequent to the systematic review ( Table 6). Kempshall et al (2015) looked at MAT concomitant with cartilage repair procedures on (1) patients with more knee cartilage damage (grade 3b >1 cm² ) and (2) patients with less knee cartilage damage (grade 3b <1 cm²).^16, Functional outcomes following the procedures were similar between the 2 groups. However, implant survival (using graft failure as an endpoint) was lower among those with greater cartilage damage.

Ogura et al (2016) retrospectively reviewed patients who had undergone autologous chondrocyte implantation and MAT.^17, Seventeen patients were followed for a mean of 7.9 years. Significant improvements in clinical outcomes (visual analog scale for pain, Western Ontario and McMaster Universities Arthritis Index, 36-Item Short-Form Health Survey, and modified Cincinnati Knee Rating Scale scores) were reported in 65% of the patients. Of the 6 procedures considered failures, 4 underwent total knee arthroplasty and 2 underwent revision surgery.

Zaffagnini et al (2016) reviewed 147 patients undergoing arthroscopic bone plug-free MAT, with 48% of patients having concomitant procedures (mostly high tibial osteotomy and anterior cruciate ligament reconstruction).^18, Two survival analyses were conducted, 1 with the endpoint of surgical failure (need for revision procedures related to initial MAT) and the other with the endpoint of clinical failure (same revision procedures as a surgical failure or LKS less than 65 at final follow-up). Mean overall survival time with the surgical failure endpoint was 9.7 years (95% confidence interval, 9.1 to 10.3 years) and mean overall survival with the clinical failure endpoint was 8.0 years (95% confidence interval, 7.1 to 8.8 years). Logistic regression analysis did not reveal any variables (including concomitant procedures) affecting the surgical or clinical failure endpoints.

Table 6. Case Series of Meniscal Allograft Transplantation Plus Articular Cartilage Repair

ACI: autologous chondrocyte implantation; FU: follow-up; IKDC: International Knee Documentation Committee; KOOS: Knee Injury and Osteoarthritis Outcome Score; LKS : Lysholm Knee Score; MACI: matrix-assisted autologous chondrocyte implantation; MAT: meniscal allograft transplantation; MCKRS: modified Cincinnati Knee Rating Scale; SF-36: 36-Item Short-Form Health Survey; TAS: Tegner Activity Scale; VAS: visual analog scale; WOMAC: Western Ontario and McMaster Universities Arthritis Index.

Section Summary: Meniscal Allograft Transplantation Plus Articular Cartilage Repair

There is a limited amount of low-quality evidence on combined MAT and articular cartilage repair. The available literature has reported reductions in pain and improvements in functioning following these procedures, though studies have reported graft failures and the need for additional surgeries.

For individuals who are undergoing partial meniscectomy and concomitant repair of malalignment, focal chondral defects, and/or ligamentous insufficiency who receive MAT, the evidence includes a systematic review of case series as well as case series published after the systematic review. The relevant outcomes are symptoms, functional outcomes, and QOL. The systematic review concluded that pain and function improved following the procedure. One of the series published after the review showed that patients with more severe cartilage damage experienced favorable outcomes similar to patients with less cartilage damage. Another series published subsequently reported an overall 9.7-year survival of the implant. A limitation of the evidence is its reliance primarily on case series. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 3

Collagen Meniscus Implants

Clinical Context and Therapy Purpose

The purpose of collagen meniscal implants (CMIs) is to provide a treatment option that is an alternative to or an improvement on existing therapies, such as partial meniscectomy without a meniscal implant, in patients with who are undergoing partial meniscectomy.

The following PICO was used to select literature to inform this review.

P opulations

The relevant population of interest is individuals who are undergoing partial meniscectomy.

Interventions

The therapy being considered is CMIs. A CMI is sutured into place on a meniscal rim and is intended for use with a partial meniscectomy.

Comparators

Comparators of interest include partial meniscectomy without a meniscal implant..

Outcomes

The general outcomes of interest are symptoms, functional outcomes, and quality of life.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

Systematic Reviews

Two systematic reviews, one by Harston et al (2012)^19, and the other by Warth et al (2015)^20, are summarized in Table 7. A third, by Zaffagnini et al (2015),^21, focused only on studies assessing postoperative magnetic resonance imaging evaluations, which included 6 studies, none of which was an RCT and all of which were included in the Warth et al (2015) review. We do not discuss the Zaffagnini et al (2015) review further. Houck et al (2018) published the results of a systematic review that included multiple scaffold implantations including CMI.^22, No studies in addition to those previously summarized by Warth et al (2015)^20, were cited in this systematic review and Houck et al (2018) are not discussed further.

Table 7. Summary of Systematic Reviews for Collagen Meniscus Implants

CMI: collagen meniscus implant; FU: follow-up; LKS : Lysholm Knee Score; TAS: Tegner Activity Scale.

The quality of the studies included in the systematic reviews was generally rated as low. Tables 8 and 9 summarize select studies (2 RCTs, 2 cohorts) included in the systematic reviews. A large RCT from the manufacturers of MenaFlex (Rodkey et al [2008]^23,) was conducted under a U.S. Food and Drug Administration investigational device exemption. Only TAS scores in the chronic arm (but not the acute arm) differed significantly between the CMI and partial meniscectomy only groups. Kaplan-Meier analysis suggested a modest 10% increase in survival in the chronic CMI group.

Randomized Controlled Trials

An independent research group published results from an RCT, reported by Linke et al (2006), comparing high tibial valgus osteotomy alone with osteotomy plus CMI.^24, Arthroscopy in the CMI group showed 35% complete healing, 30% partial healing requiring resection of the posterior part of the implant, and 35% with only small remains of the CMI left. Complications included implantation in insufficiently vascularized tissue, sutures cutting into the implant, inadequate fixation to the rim, destruction of the implant in an unstable knee joint or with premature loading postoperatively, allergic reaction to the xenogenic collagen implant, avulsion of the implant with joint blocking, and infection. Pain and function scores did not differ significantly between the CMI and control groups.

Observational Studies

Zaffagnini et al (2011) compared outcomes of 18 patients who chose CMI with 18 patients who chose partial medial meniscectomy, with a minimum 10-year follow-up.^25, The 2 groups were comparable at baseline. No significant differences were found in the LKS and Yulish scores. Independent and blinded radiographic evaluation showed significantly less medial joint space narrowing in the CMI group (0.48 mm) than in the partial meniscectomy group (2.13 mm). This study had the potential for selection bias.

A retrospective review by Bulgheroni et al (2015) of 34 patients (17 CMI, 17 partial medial meniscectomies) found no significant differences between the groups for pain and function scores at an average of 9.6 years of follow-up.^26,

Table 8. Summary of Study Characteristics for Collagen Meniscus Implants

CMI: collagen meniscus implant; FU: follow-up; RCT: randomized controlled trial.

Table 9. Summary of Study Results for Collagen Meniscus Implants

CMI: collagen meniscus implant; Ctrl: control; IKDC: International Knee Documentation Committee; LKS : Lysholm Knee Score; NS: not significant; TAS: Tegner Activity Scale; VAS: visual analog scale.a Chronic only. b Higher scores reported by CMI group vs control group.

Section Summary: Collagen Meniscal Implants

Evidence for the use of CMI in patients undergoing partial meniscectomies consists of 2 systematic reviews, the most recent including 674 patients. The reviews reported overall positive results with CMI, but the quality of the included studies (RCTs and observational studies) was low. Radiologic evaluation showed destruction and/or absorption of the implant in a very large portion of patients

For individuals who are undergoing partial meniscectomy who receive collagen meniscal implants (CMIs) , the evidence includes (2) two systematic reviews primarily of case series. The relevant outcomes are symptoms, functional outcomes, and quality of life (QOL). The reviews reported overall positive results with the CMI, but the quality of the selected studies (RCTs, observational studies) was low. Radiologic evaluations have shown reductions in the size of the implant in a large portion of patients. The evidence is insufficient to determine the effects of the technology on health outcomes.

SUPPLEMENTAL INFORMATION

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Clinical Input 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.

2011 Input

In response to requests, input was received from 1 physician specialty society (3 reviewers) and 3 academic medical centers while this policy was under review in 2011. Input considered combined meniscal allograft transplantation (MAT) and focal cartilage repair procedures to be medically necessary for patients younger than 55 years of age who have failed conservative treatment. Reviewers agreed that the collagen meniscus implant is investigational, although some considered it to be both investigational and medically necessary for some patients.

2008 Input

In response to requests, input was received from 1 physician specialty society and 3 academic medical centers while this policy was under review in 2008. Although long-term effects on joint space narrowing were unknown, all reviewers considered MAT to be beneficial in selected patients, with evidence of short to intermediate pain relief when performed in younger patients who had a prior meniscectomy and disabling knee pain. Contraindications noted were uncorrected instability, uncorrected malalignment, and the presence of significant articular disease.

Practice Guidelines and Position Statements

Guidelines or position statements will be considered for inclusion in ‘Supplemental Information’ if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

International Meniscus Reconstruction Experts Forum

The International Meniscus Reconstruction Experts Forum (2015) published consensus statements on the practice of MAT (see Table 10).^2, The Forum's statements included guidance on indications, graft procurement and preparation, surgical technique, and rehabilitation.

Table 10. Select Consensus Statements on the Practice of MAT

MAT: meniscal allograft transplantation; OA: osteoarthritis.

National Institute for Health and Care Excellence

The guidance from the National Institute for Health and Care Excellence (2012) stated that the evidence on "partial replacement of the meniscus of the knee using a biodegradable scaffold raises no major safety concerns," but evidence for any advantage of the procedure over standard surgery was limited.^27,

American Academy of Orthopaedic Surgeons

The American Academy of Orthopaedic Surgeons (2009) updated its position in 2014, still recommending MAT for active people younger than 55 years old, with the goal of replacing the meniscus cushion before the articular cartilage is damaged.^28, The website also notes that "synthetic (artificial) meniscal tissue has been tried, but there is conflicting information at this time."

U.S. Preventive Services Task Force Recommendations

Not applicable.

Medicare National Coverage

The Centers for Medicare & Medicaid Services (2010) issued a national noncoverage determination for the collagen meniscus implant.^29,A number of concerns regarding the efficacy and safety were raised by the Centers for Medicare & Medicaid Services analysis, which compared data reported to the Food and Drug Administration and published data. Concerns included an increased number of reoperations and a higher serious adverse event rate than in the control group. Centers for Medicare & Medicaid Services concluded that the collagen meniscus implant does not improve health outcomes in the Medicare population and that collagen meniscus implant is not reasonable and necessary for the treatment of meniscal injury or tear.

Ongoing and Unpublished Clinical Trials

Currently, ongoing and unpublished trials that might influence this review are listed in Table 11.

Table 11. Summary of Ongoing Trials

References

1. Cvetanovich GL, Yanke AB, McCormick F, et al. Trends in Meniscal Allograft Transplantation in the United States, 2007 to 2011. Arthroscopy. Jun 2015; 31(6): 1123-7. PMID 25682330
2. Getgood A, LaPrade RF, Verdonk P, et al. International Meniscus Reconstruction Experts Forum (IMREF) 2015 Consensus Statement on the Practice of Meniscal Allograft Transplantation. Am J Sports Med. May 2017; 45(5): 1195-1205. PMID 27562342
3. Frank RM, Cole BJ. Meniscus transplantation. Curr Rev Musculoskelet Med. Dec 2015; 8(4): 443-50. PMID 26431702
4. Elattar M, Dhollander A, Verdonk R, et al. Twenty-six years of meniscal allograft transplantation: is it still experimental? A meta-analysis of 44 trials. Knee Surg Sports Traumatol Arthrosc. Feb 2011; 19(2): 147-57. PMID 21161170
5. Hergan D, Thut D, Sherman O, et al. Meniscal allograft transplantation. Arthroscopy. Jan 2011; 27(1): 101-12. PMID 20884166
6. Rosso F, Bisicchia S, Bonasia DE, et al. Meniscal allograft transplantation: a systematic review. Am J Sports Med. Apr 2015; 43(4): 998-1007. PMID 24928760
7. Smith NA, Parsons N, Wright D, et al. A pilot randomized trial of meniscal allograft transplantation versus personalized physiotherapy for patients with a symptomatic meniscal deficient knee compartment. Bone Joint J. Jan 2018; 100-B(1): 56-63. PMID 29305451
8. Verdonk PC, Demurie A, Almqvist KF, et al. Transplantation of viable meniscal allograft. Survivorship analysis and clinical outcome of one hundred cases. J Bone Joint Surg Am. Apr 2005; 87(4): 715-24. PMID 15805198
9. Hommen JP, Applegate GR, Del Pizzo W. Meniscus allograft transplantation: ten-year results of cryopreserved allografts. Arthroscopy. Apr 2007; 23(4): 388-93. PMID 17418331
10. van der Wal RJ, Thomassen BJ, van Arkel ER. Long-term clinical outcome of open meniscal allograft transplantation. Am J Sports Med. Nov 2009; 37(11): 2134-9. PMID 19542303
11. Vundelinckx B, Bellemans J, Vanlauwe J. Arthroscopically assisted meniscal allograft transplantation in the knee: a medium-term subjective, clinical, and radiographical outcome evaluation. Am J Sports Med. Nov 2010; 38(11): 2240-7. PMID 20724642
12. Harris JD, Cavo M, Brophy R, et al. Biological knee reconstruction: a systematic review of combined meniscal allograft transplantation and cartilage repair or restoration. Arthroscopy. Mar 2011; 27(3): 409-18. PMID 21030203
13. Stone KR, Adelson WS, Pelsis JR, et al. Long-term survival of concurrent meniscus allograft transplantation and repair of the articular cartilage: a prospective two- to 12-year follow-up report. J Bone Joint Surg Br. Jul 2010; 92(7): 941-8. PMID 20595111
14. Farr J, Rawal A, Marberry KM. Concomitant meniscal allograft transplantation and autologous chondrocyte implantation: minimum 2-year follow-up. Am J Sports Med. Sep 2007; 35(9): 1459-66. PMID 17435058
15. Rue JP, Yanke AB, Busam ML, et al. Prospective evaluation of concurrent meniscus transplantation and articular cartilage repair: minimum 2-year follow-up. Am J Sports Med. Sep 2008; 36(9): 1770-8. PMID 18483199
16. Kempshall PJ, Parkinson B, Thomas M, et al. Outcome of meniscal allograft transplantation related to articular cartilage status: advanced chondral damage should not be a contraindication. Knee Surg Sports Traumatol Arthrosc. Jan 2015; 23(1): 280-9. PMID 25432522
17. Ogura T, Bryant T, Minas T. Biological Knee Reconstruction With Concomitant Autologous Chondrocyte Implantation and Meniscal Allograft Transplantation: Mid- to Long-term Outcomes. Orthop J Sports Med. Oct 2016; 4(10): 2325967116668490. PMID 27803938
18. Zaffagnini S, Grassi A, Marcheggiani Muccioli GM, et al. Survivorship and clinical outcomes of 147 consecutive isolated or combined arthroscopic bone plug free meniscal allograft transplantation. Knee Surg Sports Traumatol Arthrosc. May 2016; 24(5): 1432-9. PMID 26860105
19. Harston A, Nyland J, Brand E, et al. Collagen meniscus implantation: a systematic review including rehabilitation and return to sports activity. Knee Surg Sports Traumatol Arthrosc. Jan 2012; 20(1): 135-46. PMID 21695465
20. Warth RJ, Rodkey WG. Resorbable collagen scaffolds for the treatment of meniscus defects: a systematic review. Arthroscopy. May 2015; 31(5): 927-41. PMID 25595693
21. Zaffagnini S, Grassi A, Marcheggiani Muccioli GM, et al. MRI evaluation of a collagen meniscus implant: a systematic review. Knee Surg Sports Traumatol Arthrosc. Nov 2015; 23(11): 3228-37. PMID 24993568
22. Houck DA, Kraeutler MJ, Belk JW, et al. Similar clinical outcomes following collagen or polyurethane meniscal scaffold implantation: a systematic review. Knee Surg Sports Traumatol Arthrosc. Aug 2018; 26(8): 2259-2269. PMID 29340746
23. Rodkey WG, DeHaven KE, Montgomery WH, et al. Comparison of the collagen meniscus implant with partial meniscectomy. A prospective randomized trial. J Bone Joint Surg Am. Jul 2008; 90(7): 1413-26. PMID 18594088
24. Linke RD, Ulmer M, Imhoff AB. Replacement of the meniscus with a collagen implant (CMI). Oper Orthop Traumatol. Dec 2006; 18(5-6): 453-62. PMID 17171330
25. Zaffagnini S, Marcheggiani Muccioli GM, Lopomo N, et al. Prospective long-term outcomes of the medial collagen meniscus implant versus partial medial meniscectomy: a minimum 10-year follow-up study. Am J Sports Med. May 2011; 39(5): 977-85. PMID 21297005
26. Bulgheroni E, Grassi A, Bulgheroni P, et al. Long-term outcomes of medial CMI implant versus partial medial meniscectomy in patients with concomitant ACL reconstruction. Knee Surg Sports Traumatol Arthrosc. Nov 2015; 23(11): 3221-7. PMID 24990662
27. National Institute for Health and Care Excellence (NICE). Partial replacement of the meniscus of the knee using a biodegradable scaffold: guidance [IPG430]. 2012; https://www.nice.org.uk/guidance/IPG430. Accessed February 20, 2024.
28. American Academy of Orthopaedic Surgeons. OrthoInfo: Meniscal transplant surgery. 2014; https://orthoinfo.aaos.org/en/treatment/meniscal-transplant-surgery/. Updated March 2021. Accessed February 20, 2024.
29. Centers for Medicare and Medicaid Services (CMS). Decision Memo for COLLAGEN MENISCUS IMPLANT (CAG-00414N). 2010; https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=235. Accessed February 20, 2024.

Codes

Applicable Modifiers

As per correct coding guidelines.

Policy History