Treatment of lateral knee joint pain with artificial lateral meniscus prosthesis after meniscectomy.

Meniscal tears are the most common knee injury, resulting in approximately 61
meniscectomies per 100,000 patients annually of which ~40% of the procedures is
performed in lateral menisci.[1] In the Netherlands, in 2010, approximately
42,000 meniscectomies were performed annually and, in the US, approximately
500,000 patients are subject to partial or total meniscectomy. Meniscectomy
results in impaired function of the meniscus and decreases the contact area by
up to 75% and increase contact pressures by up to 300% [2]. Clinical and
radiological studies have shown that most patients improve clinically
post-meniscectomy, but that partial or complete loss of the meniscus promotes
in 40% of the post-meniscectomy patients the early development and progression
of Knee Osteoarthritis 5-20 years post-surgery [3]. Chatain, et al. [4]
outlines that 14% of these post-meniscectomy patients demonstrates the rapid
onset of symptomatic unicompartmental pain in the meniscus-deficient knee, the
so-called post-meniscectomy pain syndrome.

As no cure for the post-meniscectomy pain syndrome patient is currently
available, most patients endure the remaining pain and experience gradual loss
of their mobility. Therefore, patients have to adapt their daily life
activities. The symptoms often have a profound effect on the quality of life
(QoL), affecting both physical functioning and psychological parameters. There
are no specific clinical guidelines for the post-meniscectomy pain syndrome but
treatment is mostly conservative analogue to the treatment guidelines for knee
osteoarthritis [5] of which the Standard of Care (SOC) treatment scheme is as
follows:
• First line of treatment is a combination of non-pharmacological interventions
such as exercise, education and weight loss programs, physical therapy and use
of assistive devices. During this stage of the disease, physicians often
recommend soft pain medication, such as paracetamol.
• Second line of treatment involves stronger pain medication, such as
nonsteroidal anti-inflammatory drugs (NSAIDs) and the even less-desirable
opioids. Also, corticosteroid injections are applied directly into the knee
joint. These treatments reduce pain but do not prevent continuous joint
degeneration. This will eventually result in a more severe KOA, for which
pharmacological pain intervention is no longer sufficient. With a mean age at
KOA diagnosis of 54 years-old, the average time on pain medication preceding
the third line of treatment is 13 years for the regular patient (K/L grade 2)
[6].
• Third line and final treatment: once most articular cartilage is degenerated
and first- and second-line conservative therapies are no longer effective to
delay or prevent disease progression, surgical treatment is often necessary.
The SOC surgical treatment for end-stage KOA is Total Knee Arthroplasty (TKA)
or Unicompartmental Knee Arthroplasty (UKA). This highly invasive surgical
intervention removes the diseased bone and cartilage from respectively one or
both knee joint compartments, which is replaced with an artificial joint made
of synthetic materials. TKA have demonstrated improved function, reduced pain
and improved QoL for patients [7]. For ease of reading, TKA and UKA are grouped
as *TKA* in the remainder of this document, unless specifically indicated
separately. A distinct limitation of TKA is that it is a suboptimal treatment
option in patients under the age of 65 years since younger active and
high-demand patients are at a greater risk for prosthesis failure due to
reduced durability of the TKA. Consequently, the patients are likely to outlive
their prosthesis and a revision surgery is required to replace the original
implant with a new knee replacement. This is a more complex procedure
associated with higher complication rates, extended hospitalization, and
unsatisfactory functional outcomes [8]. After the revision TKA no other
treatment options are possible, leaving the patient immobile and wheelchair
bound when the prosthesis stops functioning.

The development of the lateral meniscus prosthesis focuses on post-meniscectomy
pain syndrome patients, with limited underlying cartilage damage (Kellgren
Lawrence scale 0-2), who remain with unicompartmental pain in the lateral
meniscus-deficient knee and reduced mobility. Clinical and radiological studies
have shown that most patients improve clinically, but that early onset
osteoarthritis can develop later[9]. This is the patient group that now spends
on average 13 years on a non-surgical regimen of pain medication [6].
Obviously, the non-surgical natural history of post-meniscectomy syndrome is
very unfavorable, and the pain remains also on the longer term. This is also
confirmed by the non-surgical control group in the study by McKeon et al. in
which the patients with a non-operative treatment perform stable low[10].
Treatment options for patients with meniscus deficient knees are limited to
transient conservative treatment options (i.e., first and second line of
treatment of SOC). This treatment often falls short, and the pain remains on an
unacceptable level in many patients. Furthermore, in a meniscus deficient knee
the KOA progresses until it reaches end-stage KOA condition, then the only
solution is a TKA whereby the degenerative (part of the) joint is removed and
replaced. There is a large treatment gap between the first knee pain after
meniscectomy and the eligibility for a TKA. Hence, there is a strong unmet need
for a durable and cost-effective treatment solution that will relieve chronic
knee pain and regain mobility in symptomatic post-meniscectomy patients. Such
treatment could save the knee joint and delay or prevent the need for a knee
joint replacement.

The LMP is intended to provide unicompartmental pain relief in the
meniscus-deficient knee by simulating the function of the natural meniscus. The
LMP is intended to restore the function of the natural meniscus and
redistribute loads transmitted across the knee joint.

The primary objective of the clinical investigation is to evaluate the safety
of the LMP system within 1 year after implantation in terms of adverse events
and prosthesis integrity. Outcomes: AEs and prosthesis extrusion on MRI 12
months post-operatively.

Secondary objectives are:
• To demonstrate clinical performance within 2 years in terms of pain relief
and maintenance of function (Outcomes: KOOS, Pain VAS, OKS, Lysholm scale,
Tegner Activity Scale).
• To record changes in general well-being (Outcomes: SF-36, EQ-5D-5L, WORQ).
• To identify wet biomarkers as objective measures for clinical status (urine,
blood, synovial fluid)

Prospective, multi-center, open label, single arm clinical investigation

Implantation with the lateral meniscus prosthesis (LMP) system.

The intended clinical benefits of the LMP system are:

• Pain relief in the lateral compartment of the knee
• Increased functional activity
• Symptom relief
• Improved Quality of Life

The following potential Adverse Device Effects have been identified:
• Pain discomfort and/or Range of Motion (RoM) impairment, caused by
oversizing, undersizing or wrong placement of the meniscus prosthesis
• Pain discomfort and/or RoM impairment, caused by impingement of the meniscus
prosthesis
• Breakage of the meniscus prosthesis, potentially leading to pain discomfort
and requiring consecutive surgery to remove or replace the prosthesis
• Wear of the meniscus prosthesis, potentially leading to breakage, pain
discomfort and/or synovitis
• Wear of the fixation tape, potentially leading to breakage and/or synovitis
• Impingement of implant components between the articular surfaces as a result
of incorrect positioning during surgery or after implant failure, potentially
resulting in changes to the cartilage and/or bone tissue
• Post-operative infection of the joint, which requires consecutive surgery
with rinsing of the joint, prolonged antibiotics, and possible removal of the
implant.
• Neurovascular damage during surgery: especially drilling of the posterior
drill hole may damage the neurovascular structures posterior in the knee
(popliteal nerve, artery, and vein)