A range of ground-breaking genetic tests that could help predict whether joint replacements succeed or fail were this week launched to the medical community at the British Orthopaedic Association’s annual congress.
The MHRA-registered Orthotype tests from ExplantLab were developed with the backing of Innovate UK and the Academic Health Science Network for the North East and North Cumbria (AHSN NENC) in collaboration with Newcastle University and University Hospital North Tees, Nuffield Health Tees Hospital, Hospital for Special Surgery (New York) and Royal Perth Hospital. Using next-generation genetic sequencing, the tests identify genetic markers in saliva or blood samples for specific variations of HLA genes which, if found, indicate patients will develop an adverse reaction to the cobalt chrome (CoCr) contained in many joint replacement implants.1
David Langton from ExplantLab explains: “By sequencing DNA in saliva swabs and blood tests from 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 component, often referred to as an adverse reaction to metal debris (ARMD) or metal hypersensitivity.”
Unmet need in orthopaedics
Worldwide it is thought that between 10-20% of total joint arthroplasties (TJA) are revision surgeries, required because the original implants have failed,2 with up to 44% of failed knee joint replacements showing evidence of an adverse CoCr reaction.3 While the complications linked to revision surgery are similar in nature to those associated with a first-time replacement, the risk of any single complication occurring is significantly higher.4 This places a considerable toll on both patients and health services.
To date, a lack of specific implant-related hypersensitivity diagnostic tools5 has made it difficult to diagnose metal hypersensitivity in post-operative patients. Risk factors have been unclear, meaning surgeons have been unable to predict how well a patient may tolerate an implant.
Aiding clinical decision-making
By assessing whether a patient is likely to develop metal hypersensitivity, the Orthotype suite of tests can help ensure more implants are well-tolerated first-time round, in turn lessening the need for post-operative chronic pain management and repeat surgery. As a result, this could deliver better orthopaedic outcomes for patients and help ease the clinical backlogs that have built up since the pandemic.6
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 undoubtedly have an adverse reaction to implants that are made from cobalt chrome alloy. In the age of personalised medicine, this type of innovation represents a significant advance in orthopaedic care, providing surgeons with information about the host factors that influence the outcome of surgery. This will help them and their patients to make better decisions about the best treatment.”
Proven algorithm
The science behind Orthotype is based on 15 years of international research involving over 600 patients, 176 of whom experienced prosthesis failure.1 It found that metal hypersensitivity is associated not only with patient age, gender, and the levels of metal debris in the blood, but also the presence of certain HLA class II alleles.1 Researchers used this insight to inform and validate an algorithm to predict the likelihood of development of a serious disorder called ‘aseptic lymphocyte-dominant vasculitis-associated lesion’ (ALVAL) at an accuracy (1.8% probability error) suitable for clinical use. The addition of blood metal concentration testing means Orthotype can also be used to determine the cause of post-replacement pain and inflammation (with a sensitivity and specificity of around 90%).1
Potential benefits
It is hoped that the launch of Orthotype could herald a new surgical era of personalised medicine in orthopaedics in which individuals routinely undergo genetic testing prior to receiving medical implants. AHSN NENC, which supported the research and development of Orthotype, believe that as well as relieving the burden faced by patients, Orthotype’s use in standard clinical practice could deliver cost savings to the NHS. Russell Watkins, Commercial Director at AHSN for North East and North Cumbria explains: “Orthotype represents a much-needed innovation in orthopaedics which has the potential to provide significant financial implications for healthcare systems, through the avoidance of repeat surgery. The AHSN NENC exists to spread innovation at pace through the NHS and I believe the adoption of innovations, such as Orthotype, will lead the way to improving patient health outcomes”.
Surgeons and clinicians can order the suite of Orthotype tests via the pathology laboratory services in their hospitals, including a post-operative combined test that can be used to diagnose metal sensitivity in people who have already undergone surgery – see more information on the ExplantLab website: https://www.explantlab.com/orthotype-test.
A saliva-based home test kit is also available for pre-operative joint replacement patients to order online via the ExplantLab website.
References
[1] Langton DJ, Bhalekar RM, et al. The influence of HLA genotype on the development of metal hypersensitivity following joint replacement. Commun Med (Lond). 2022 Jun 24;2:73. doi: 10.1038/s43856-022-00137-0. Erratum in: Commun Med (Lond). 2022 Jul 15;2:91.
[2] Akil S, et al. Metal hypersensitivity in total hip and knee arthroplasty: Current concepts. J Clin Orthop Trauma. 2018 Jan-Mar;9(1):3-6. doi: 10.1016/j.jcot.2017.10.003. Epub 2017 Oct 10.
[3] Ng VY, Lombardi AV Jr, Berend KR, Skeels MD, Adams JB. Perivascular lymphocytic infiltration is not limited to metal-on-metal bearings. Clin Orthop Relat Res. 2011 Feb;469(2):523-9. doi: 10.1007/s11999-010-1570-7. PMID: 20878289; PMCID: PMC3018196.
[4] West Suffolk NHS Foundation Trust. Hip replacement revision. 2021. Available at https://www.wsh.nhs.uk/CMS-Documents/Patient-leaflets/TraumaandOrthopaedics/5060-2-Revision-Hip-Replacement.pdf. [Last accessed: Sept 2022]
[5] Schoon J, Ort MJ, Huesker K, Geissler S and Rakow A (2019) Diagnosis of Metal Hypersensitivity in Total Knee Arthroplasty: A Case Report. Front. Immunol. 10:2758.
[6] The Health Foundation. Waiting for Care. 2021. Available from https://www.statista.com/statistics/1099162/hip-replacement-procedures-in-england/. [Last accessed: Sept 2022]
