Impact case study database

The discovery of novel myositis-specific autoantibody (MSAs) by the Bath group and studies highlighting their clinical utility in patient stratification have transformed the clinical approach to investigation and treatment of adults and children with myositis. This has benefited both Industry and patients, particularly those patients with anti-SAE, anti-Zo and anti-EIF3 who would otherwise be considered autoantibody negative.

Impact on industry

The anti-SAE and anti-Zo autoantibodies, discovered by the Bath serology team, have to-date been incorporated into diagnostic kits (e.g. ELISA, line blot) sold by the following manufacturers: EUROIMMUN, D-Tek, Alphadia, Inova, RDL, and ARUP [ A]. In contrast to the traditional Immunoprecipitation (IPP) technique, these kits offer faster, cheaper autoantibody characterisation, without the need for specialist expertise, meaning that more patient samples can now be tested for these biomarkers. A 2019 survey, conducted by the Bath serology group, of 111 clinical experts (based at 65 institutions across 6 continents and belonging to the International Myositis Assessment and Clinical Studies (IMACS) Group) revealed the widespread accessibility of these diagnostic tools:

“ELISA was reported to be the most widely used MSA detection technique worldwide, used by 46% of respondents’ local laboratories. This was followed by the line blot, used by 37% of respondents’ laboratories. In Europe, the market was dominated by the EUROIMMUN line blot; 74% of European respondents’ local laboratories used a line blot and 48% the EUROIMMUN line blot” [ B].

The IMACS survey also showed that, of the nine most popular commercial assay manufacturers, two thirds include anti-SAE and 1 in 9 anti-Zo, discovered at Bath [ A and B].

As the primary European manufacturer of assay kits [ c], EUROIMMUN report that, since the inclusion of anti-SAE on their line blot in 2013, there has been a 50 fold increase in its use, with 217,281 strips being tested worldwide in 2019, generating an estimated revenue of GBP5,700,000 (based on UK price of GBP26.50 per strip) [ C, D].

A statement from the Chairman of the Executive Board for EUROIMMUN, leader in autoimmune serology diagnostics [ B, C], reads as follows:

“The inclusion of this marker [anti-SAE1] was instrumental to EUROIMMUN's quest to cover all relevant antibodies specific to, and associated with, myositis...The [Bath] group also identified anti-Zo autoantibodies in myositis patients. EUROIMMUN will implement this new important marker into their new myositis profiles” [ C].

Impact on patient wellbeing and clinical practice/policy

A Consultant Paediatric Rheumatologist at the Leeds Teaching Hospitals NHS Trust described how testing for anti-HMG CoA autoantibody, identified by the Bath serology group as a biomarker of JDM, after several years of difficulties in understanding the condition of his patient, finally enabled a definitive diagnosis to be made:

“[W]e were really struggling to understand her diagnosis in 2015. She had presented around 5 years earlier with rashes and weakness. [T]he result of positive HMG CoA antibodies was very helpful and contributed significantly to a confident diagnosis of HMG CoA antibody associated autoimmune myopathy. This has helped the young person psychologically to a large extent and has allowed more directed treatment, which I am confident has allowed a better outcome than if we had continued to follow standard pathways, with the uncertainty of diagnosis ‘hanging over us” [ E].

At present there are no guidelines for the investigation or treatment of patients with myositis. Guidelines for the management of patients with myositis are currently under development by the British Society of Rheumatology (Neil McHugh and Sarah Tansley are both contributing to this project). Despite a lack of guidelines, it is clear that the Bath serology group has contributed to a substantial change in the overall diagnostic approach, by highlighting the importance of autoantibody testing. In the IMACS group survey:

“…the majority of participants reported that MSA testing influenced their diagnostic confidence (83%), the information they relayed to their patients on prognosis (86%), further investigations planned (81%), and even their recommended treatment (73%)” [ B].

A renowned Manchester-based Professor and Consultant Rheumatologist, who oversees the collection of adult myositis samples for the clinical and scientific UK Myositis Network (UKMYONET), gave the following statement:

“The Bath serology group have changed the pattern of practice in the work-up and management of myositis cases here in the UK and elsewhere, through the discovery of new autoantibodies, and their ability to measure those not detectable by other means. Certainly, their work has helped reduce diagnostic delay and other unnecessary investigations. They have helped shape NHS England clinical commissioning policy for treatment of myositis and by demonstrating the presence of myositis autoantibodies have allowed more patients access to effective treatment such as Rituximab” [ F].

NHS England Rituximab Clinical Commissioning Policy 2018 concluded that there was sufficient evidence to support the routine commissioning of rituximab in the treatment of adult myositis patients who have autoantibodies relevant to myositis [ G]. This includes those autoantibodies discovered by the Bath group meaning that approximately 60 myositis patients a year are able to receive rituximab, which they would otherwise be denied.