MICA: A UK-wide networking partnership to facilitate collaborative research in the idiopathic inflammatory myopathies

Objective
To improve the way we treat sufferers with unexplained inflammation in muscle (myositis), by bringing together UK experts, helping research activities, increasing awareness of the disease, improving the way we diagnose and monitor, and improving training opportunities for the UK health-care community.

Background
Unexplained inflammation in muscles is known as "myositis", a condition that affects about 15 in 100,000 people. The muscles affected usually include those around the shoulders and hips, but other parts of the body can be affected. Unlike other muscle diseases, such as muscular dystrophy, the inflammation in myositis is potentially treatable, although the drugs used can be toxic and don't always work. As myositis is uncommon, doctors are often not familiar with recognizing the disease. Delays in diagnosis may lead to irreversible muscle damage, so even after treatment has started, sufferers often remain weak and disabled, leading to significant illness burden on families, carers and society.

The way we diagnose myositis varies widely, which can lead to a wrong diagnosis being made, and use of toxic treatments that may cause harm. Current treatments for myositis are mostly "borrowed" from other inflammatory musculoskeletal diseases. There is no national or international guidance about treatments. We need to improve the care given to myositis sufferers by combining expertise across different medical disciplines. A non-funded organisation, UKMYONET, created by the applicants, aims to share expertise and generate ideas for future research studies and drug trials. An existing UK network working on childhood myositis, the Juvenile Dermatomyositis Research Group, also closely aligns with UKMYONET.

Aim 1: To support current and future myositis research activities and optimize their quality, quantity and success in the UK for years to come. Myositis is rare, meaning that many samples are needed for research and cannot be collected in a single hospital. Instead, collection has to be done by many collaborating muscle experts and hospitals, requiring careful and detailed organisation. The success of this grant application would allow a coordinator to support a coordinated collection of clinical information and blood samples from myositis sufferers, establish UKMYONET meetings as an important national event, and help collaborations with patient-run organizations.

Aim 2: To improve the way we work together to manage myositis better. This grant will help support the collaborating applicants to work together to develop further scientific work aimed at improving the tests that we use to diagnose and monitor myositis. We would like to diagnose myositis earlier with a minimum of delay, tease out the different forms of myositis with ease, and standardize myositis treatment across the UK, with a view to improving future outcomes for patients. The grant will help to support ongoing research activities to make these activities happen, by further developing a study resource of myositis patients.

Aim 3: To improve training opportunities in the field of myositis and the way that sufferers are cared for. We wish to bring different medical experts together, as myositis is truly a multisystem disease: currently these specialists tend to work in "silos", do not attend meetings out of their discipline, may read different literature, and thus have different approaches to treatment. Current funding streams may not attract the spectrum of expertise needed, and exchange of knowledge is poor across disciplines. Health care professionals need more understanding about the variation of how myositis may present, and this can be tackled by improving standards of care and treatment for different types of myositis. Training workshops will be established in national centres of expertise.

The term myositis refers to a group of rare autoimmune diseases affecting about 10,000 UK patients, the idiopathic inflammatory myopathies (IIM), which cause muscle weakness and disability. It is imperative to bring together IIM expertise and knowledge in the UK to improve infrastructure and coordinate research, clinical trial and training activities. To address this, a clinical and scientific network, UKMYONET, was established by the applicants. Funding for laboratory-based research work on samples recruited through UKMYONET has been available via an Arthritis Research UK programme grant, but no funding supports UKMYONET administrative costs. Similarly, there is no current professional funding to support training opportunities or UKMYONET meetings.

The partnership grant would provide funding otherwise not available by other funding streams. The funds requested will facilitate coordinated UK-wide research activities including genetics, serology, and fundamental cellular mechanisms, and align parallel efforts for adults and children with IIM. Research activities will use datasets including ongoing collection of a core clinical dataset, establishment of a UK-wide adult IIM prospective cohort study, a national treatment outcomes registry to assess the safety and efficacy of novel therapies and establishment of a national myositis biobank. The resource will allow implementation of international research activities to be conducted using UK-based resources and expertise, including validation of new classification criteria and definitions of disease improvement/worsening/remission, and consensus on diagnostic and treatment approaches. Training workshops and visits will allow health care professionals to gain disease-specific experience.

Overall, a more coordinated, collaborative approach and sharing of expertise for IIM research and patient care is anticipated to improve translation of existing/emerging research outputs and knowledge into clinical practice.

Pharma: Stakeholders in existing and in-development biologic therapies, Servier, BMS and Novartis, have recently collaborated with the applicants to test existing and novel agents in IIM as part of pharma-sponsored clinical trials. Industrial collaborations are already in place to explore regenerative technologies in chronic muscle disease. Several of the applicants are involved in a pivotal phase IIb study to increase muscle mass and endurance in sIBM. Genzyme produce enzyme replacement therapy in lysosomal storage disorders including Pompe disease, a myositis mimicker. Funding for this expensive treatment is commissioned via NHS Specialised Services. It is vital to make an accurate diagnosis for the right patients can benefit, and ensuring that patients with other neuromuscular conditions do not receive unnecessary therapy. Genzyme have sponsored previous UKMYONET meetings and support educational activities organized by the applicants.

The establishment of a novel drug registry with linked biobank is vital in a rare disease where agents are borrowed from other diseases, and not specifically licensed. Longitudinal data will enable safety signals to be monitored over time for adverse or unexpected events. Establishment of high quality data and samples combined with clinical expertise will also facilitate testing of discovery biomarker platforms, to accelerate development and commercialization of future diagnostics.

NHS England: The Department of Health has undergone a consultation exercise on Rare Diseases, and this application is of direct relevance in addressing unmet needs in orphan diseases such as IIM, where improved training opportunities, accurate diagnostics, registers and coordinated care are required. The consultation document acknowledges the need for networks as crucial for rare diseases. Helping to facilitate a biologics registry to monitor safety issues is of paramount importance, and is an obligation in Specialist NHS Commissioning.

Local stakeholders: The proposed grant will run parallel to a national drive to raise awareness of neuromuscular orphan conditions. Salford Royal NHS Foundation Trust is part of the Manchester Academic Health Science Centre, which has committed resource into a quality improvement programme around rare neuromuscular diseases, aiming to accelerate research implementation using improvement science for wider national and international dissemination.

Clinicians: Workshops will bring experts together, e.g. rheumatology, neurology, dermatology, respiratory, pathology, neurophysiology; myositis is a multisystem disease and these specialists tend to not to attend meetings out of their discipline, read different literature, and have different treatment approaches. Current funding streams may not attract the spectrum of expertise needed. An appreciation of myositis heterogeneity is required and how to recognize disease early. The network will foster UKMYONET and establish a platform for future UK myositis trial work. Cohort studies will help develop better diagnostics and antibody/other biomarker monitoring, and create standardized treatment protocols to improve standards of care for different types of myositis.

Patients: Patients and relatives will, as "end-users", benefit from anticipated improvement of quality of clinical care, and future development of new and more effective treatments for IIM, resulting in improved prognosis and quality of life. Patients will engage as part of a research user group and have input into future research priorities and academic activities.

Charities: UKMYONET already has close links with the Myositis UK patient self help support group and The Myositis Association (USA). Results and scientific output will be disseminated through the websites of these organizations. The grant will result in useful output for patients, relatives and other end-users, for example web content and information leaflets.

Timescales: Refer to pathways to impact.