Genetic tests set to reduce burden of joint replacement surgery

Woman with grandmother walking in park in autumn

A range of ground-breaking genetic tests could help predict whether joint replacements succeed or fail.

These new genetic tests are poised to help the UK meet its goal of becoming a world-leading ‘science superpower’ by 2030.

The Medicines and Healthcare products Regulatory Agency-registered Orthotype tests from ExplantLab were launched this week at the Artificial Intelligence in Orthopaedics conference at the Royal College of Surgeons.

The tests have been developed with the backing of Innovate UK and the Academic Health Science Networks for the North East and North Cumbria, in collaboration with:

  • Newcastle University
  • University Hospital of North Tees
  • Nuffield Health Tees Hospital
  • Hospital for Special Surgery, New York
  • Royal Perth Hospital, Australia

Testing for allergic reactions

Orthotype tests identify genetic markers in saliva or blood samples for specific variations of human leukocyte antigen (HLA) genes, which regulate immune responses.

These genes indicate whether patients will develop an allergic reaction to cobalt chrome, a type of metal found in many joint replacement implants.

Predicting risk

David Langton from ExplantLab explains:

By sequencing DNA in saliva swabs and blood tests from over 600 joint-replacement patients around the world, we established that those who suffered complications carried specific variations of the HLA gene family.

We then used our findings to develop a machine-learning algorithm called Orthotype that uses genetics to accurately predict whether a patient is at risk of reacting to a joint replacement made of a cobalt chrome (CoCr) component, often referred to as an allergic reaction to the joint implant.

Innovation driven by necessity

The pandemic saw the number of hip and knee replacements fall, due to the pressures on the NHS. There remains a significant backlog of cases which has led to increased waiting times.

The problem is worsened by the fact that not all joint replacements are successful. Worldwide, it is estimated that 10% to 20% of the procedures being carried out are revision surgeries, where original implants have failed. Up to 44% of failed knee joint replacements show evidence of an adverse CoCr reaction.

In addition, around 20% of patients return post-surgery with joint pain. A genetic test that can help reduce the adverse effects of implants may reduce the need for post-operative chronic pain management and repeat surgery.

This will help to deliver better orthopaedic care and health outcomes for patients as well as potentially reducing NHS waiting lists.

Innovation in othopaedics

Mr Jeremy Latham, Consultant Orthopaedic Hip Surgeon in Southampton, said:

We know that the majority of patients have an excellent outcome following joint replacement surgery. However, some people do experience an adverse reaction to implants that are made from cobalt chrome alloy.

The use of Orthotype will help us identify these patients so that we can make better decisions about the best implant for them. In the age of personalised medicine and shared decision making, this is the type of innovation that we should be adopting in orthopaedics.

Why artificial joints fail

While joint replacement operations tend to be successful, a significant number of patients return post surgery with unexplained pain and inflammation which can result in implant failure.

Sometimes this is because the joints have become unstable or infected but over the past 2 decades an allergic reaction to the ‘debris’, or metal particles, shed by a joint implant has been increasingly recognised as a contributing factor.

As well as chronic pain and inflammation, this can cause irreparable tissue damage. In the most severe cases, people can develop an autoimmune-like response to their implant, leading to a more serious disorder known as ‘metal hypersensitivity’. It is in these cases that joint revision surgery may be recommended.

Information is empowering

Sally, aged 66 from Leeds has had knee pain for over 40 years. She said:

When the pain began stopping me doing the things I wanted to, like going for long walks, I knew I needed some help. My doctor started discussing knee replacement surgery. I heard about the Orthotype research in the news and thought having the test before I had surgery would be a good idea.

Sally accessed the test on compassionate grounds from ExplantLab prior to launch.

She said:

The test was easy to do at home, and I sent it back in the post. A couple of weeks later I learned that I have the genes that might make me more likely to react badly to the most commonly used knee replacement implants.

Having this information is empowering because my doctor can use it to choose the best kind of implant for me, which makes me feel a lot more confident about having the surgery.

Personalised orthopaedic medicine

It is hoped that the launch of Orthotype could herald a new surgical era of personalised medicine in orthopaedics in which individuals undergo genetic testing prior to receiving implants.

Innovate UK, which part-funded the research into Orthotype, believe that it will relieve the burden faced by patients and the already buckling health service. Orthotype’s use in standard clinical practice is also an additional demonstration of Britain’s thriving innovation in science and technology.

Richard Hebdon, Director of Health and Life Sciences at Innovate UK said:

As health systems come under increasing pressure to serve a growing, ageing population, it is inevitable we’ll see more of a move towards personalised medicine.

The traditional one-size-fits-all approach simply will not meet the increasing complexity of society’s needs. Therefore, innovations such as Orthotype, that inform and enhance clinical decision-making on a personal, practical level, will be vital in enabling a fit-for-purpose transformation.

A transformation that could help cement Britain’s position as a leader in scientific innovation on the international stage.

First-in-class genetic tests

The MyOrthotype saliva-based home test kit is available for pre-operative joint replacement patients to order online via the ExplantLab website.

Surgeons and clinicians can order more detailed blood-based versions of the Orthotype tests via the pathology laboratory services in their hospitals. This includes a post-operative combined test that can be used to diagnose metal sensitivity in people who have already undergone surgery.

Further information

About ExplantLab

ExplantLab is an orthogenomic biotechnology company. It is Europe’s largest independent orthopaedic retrieval company and the provider of explant analysis to the NHS in the UK.

Following 15 years of international research involving over 600 patients, scientists at ExplantLab have been able to prove a link between the HLA genes and the risk of metal hypersensitivity.

Some people have genetic variations that mean their immune system will react more aggressively to CoCr debris, putting them at a higher risk of autoimmune-like reactions.

These findings were recently published in the leading scientific journal Nature Communications Medicine.

ExplantLab has the backing of Innovate UK and the Academic Health Science Network for the North East and North Cumbria, in collaboration with:

  • Newcastle University
  • University Hospital of North Tees
  • Nuffield Health Tees Hospital
  • Hospital for Special Surgery, New York
  • Royal Perth Hospital, Australia

ExplantLab has used their findings to develop a machine-learning algorithm that uses genetics to accurately predict whether a patient is at risk of reacting to a joint prosthesis made of a CoCr component.

The addition of blood metal concentration testing allows the test to also be used to determine the cause of post-replacement pain and inflammation. Blood Cancer Charity, Anthony Nolan will provide the testing services.

About Orthotype

Pre-operative tests

MyOrthotype

A consumer-focused test for patients who are waiting for joint replacement surgery. A saliva-based test kit can be ordered online and posted back to ExplantLab for genotyping.

This test informs the patient if they carry the primary at-risk genotype for an adverse reaction to metal.

Orthotype Pre Op

A more detailed blood test that can be requested by surgeons and clinicians to quantify a patient’s risk of CoCr hypersensitivity by identifying their HLA genotype. It combines this with additional patient risk factors to provide a patient specific risk profile.

Post-operative tests

Orthotype Post Op

This test combines the HLA genotyping and patient risk factors and also measures CoCr concentrations in the blood. This enables identification of an active metal reaction and the information can be used to help guide management plans and suggest whether revision surgery is required.

Orthotype Plus Ti

A combined test that identifies the same factors as Orthotype Post Op and also levels of titanium in the blood. Measurement of titanium may help diagnose abnormal wear or loosening of titanium components where applicable.

Top image:  Credit: Ridofranz, iStock, Getty Images Plus via Getty Images

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