The burden of the disease is increasing yet there is no cure
It is estimated that 9.6% of men and 18% of women over the age of 60 worldwide experience the debilitating symptoms of osteoarthritis. As people tend to live longer, and the population of people over 60 is increasing, cases of the disease are on the rise. Direct and indirect costs of osteoarthritis in the EU are already substantial: in the UK alone, total costs for adaptive aids and devices, medicines, surgery and time off work are estimated to be equivalent to 1% of the gross national product per year. The burden will be greatest in developing countries, where life expectancy is increasing and access to arthroplasty and joint replacement is not readily available. Furthermore, although there are a wide range of devices and palliative medicines available that can relieve pain and improve quality of life, there are currently no pharmaceutical products that can halt or reverse the onset of osteoarthritis.
Despite the large and growing burden of this disease, many pharmaceutical companies have reduced or altogether abandoned drug development. One of the problems is that there are currently no reliable ways of measuring whether a specific treatment is working or not. This is partly because the mechanisms which lead to the disease in different subgroups of patients are poorly understood. Moreover, although the current mind-set for treatment in this field is moving towards personalised medicine, there are no accepted methods of classifying the patients according to diagnosis methodology, prognosis and treatment plan. It is clear that a better understanding of the disease is urgently needed.
Complex algorithms to hunt for disease subtypes
By bringing together a strong team of 25 partners from European clinical centres, basic research institutes, small and medium-sized enterprises (SMEs) and pharmaceutical companies, the APPROACH consortium will combine biomedical data of more than 10 000 patients and heathy people from 8 existing cohorts into a unified bioinformatics platform. With the help of complex algorithms, bioinformaticians will comb through this central database to identify subtypes or phenotypes of osteoarthritis. These subtypes will then be validated in a longitudinal clinical study, using existing and newly-developed biological markers. Ultimately, the identification of subtypes of this disease should lead to improved drug development and diagnostic tools, allowing osteoarthritis patients to receive better, more personalised treatment.
The project will focus on knee osteoarthritis – a very common form of osteoarthritis which is a major cause of impaired mobility (particularly in women) and therefore has a high clinical burden. This form of the disease is ideal for the APPROACH database because it has been extensively examined in large groups of patients and lots of standardised data, such as x-ray and MRI measurements, is available.
Valuable tools and outcomes
At the end of the project, APPROACH will provide valuable tools, methods and definitions that will be used to optimise future clinical trials for osteoarthritis, paving the way for personalised medicine. More specifically, the main outcomes of the project will be as follows:
- an integrated bioinformatics platform which functions as a repository for clinical data, biomarker data, images, as well as storage of bio-tissues from a broad spectrum of osteoarthritis patients;
- subsets of patients based on well-defined subtypes or phenotypes of the disease;
- new biological markers for osteoarthritis based on imaging, locomotion and biochemical methods;
- validation and optimisation of the next generation imaging methodologies, human motion analysis and biochemical methods to enable more efficient diagnosis and treatment of osteoarthritis patients.
A big step towards more personalised medicine for patients
By identifying different subtypes of osteoarthritis, APPROACH will make a big step forward in helping the pharmaceutical companies develop more effective treatments for the osteoarthritis patients. Patients will reap the greatest benefits as the identification of disease subtypes will lead to improved diagnostic tools and more effective, highly personalised treatments.
Achievements & News
Knee osteoarthritis occurs when cartilage in the knee gradually wears away, resulting in pain and stiffness. When running clinical trials for new treatments for osteoarthritis, researchers need to ensure they include the right patients, i.e. people whose condition is likely to get worse during the trial. ###This is because the condition of many trial participants does not change much during the trial anyway, making it hard to assess how effective a treatment is.
When researchers from the APPROACH project were selecting patients for a study to uncover biomarkers of osteoarthritis progression, they wanted to make sure they could select patients who will progress during the observation period.
To do this, they took data from two long-term knee osteoarthritis studies to identify the best performing machine learning models. They found that the model-based selection outperforms the conventional inclusion criteria, reducing by 20–25% the number of patients who show no progression. This result could lead to more efficient clinical trials. Their findings are published in the journal Scientific Reports.
Find out more
- Read the article in full
The APPROACH project has found that a commercially-available motion-measuring technology could be used to gauge the extent of osteoarthritis as an alternative or add-on to existing diagnostic options.###
There are a number of ways that osteoarthritis (OA) progression can be measured, including x-rays, MRIs, and questionnaires, but all come with drawbacks. APPROACH studied whether a commercially-available technology called GaitSmart® could offer added value in the evaluation of knee osteoarthritis as a non-invasive, inexpensive and flexible alternative or add-on to help doctors make a diagnosis. The GaitSmart® system involves attaching six sensors to a person’s body and having them walk 15-20m at their own speed. The sensors feed data to a laptop which analyses the results. The whole process takes about 10-15 minutes and is easy to transport and set up.
GaitSmart® was found to measure different features of OA as well as offer more information than what can be gathered through a survey. It was also found that GaitSmart® can offer additional information on the severity of tissue damage as seen on conventional x-rays.
According to the project, GaitSmart® could ultimately be used in a primary care setting, where a patient presenting with suspected knee osteoarthritis could have the test carried out by a healthcare assistant, with a report made available to the GP prior to consultation. The system also allows patients to be more invested in their progress as the changes in the report are easy to identify.
Find out more
- Read the article in full
IMI osteoarthritis project APPROACH has screened the first patient in a clinical study on osteoarthritis of the knee that will pave the way for more personalised treatments for the disease. Over the next two years, 300 patients across Europe will undergo assessments on pain, mobility, cartilage and bone condition, and inflammation. ###Information gathered will help the project to identify biological markers (biomarkers) of disease progression. ‘Currently, all osteoarthritis patients are treated the same. The quality of clinical trials and personalised treatments by doctors will improve tremendously when disease subtypes can be diagnosed. Biomarkers will help to push this forward,’ said Anne Karien Marijnissen, coordinator of the APPROACH clinical study. The project’s seven-strong Patient Council was influential in the set up of the clinical study, collaborating on communications and study design (especially with reference to the burden on study participants) and reviewing the research protocol and patient informed consent forms.
ParticipantsShow participants on map
- Glaxosmithkline Research And Development LTD., Brentford, Middlesex, United Kingdom
- Institut De Recherches Internationales Servier Iris, Suresnes, France
- Merck Kommanditgesellschaft Auf Aktien, Darmstadt, Germany
Universities, research organisations, public bodies, non-profit groups
- Academisch Ziekenhuis Leiden, Leiden, Netherlands
- Arthritis Research UK, Chesterfield, United Kingdom
- Assistance Publique Hopitaux De Paris, Paris, France
- Centre National De La Recherche Scientifique Cnrs, Paris, France
- Diakonhjemmet Sykehus As, Oslo, Norway
- Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Erlangen, Germany
- Lunds Universitet, Lund, Sweden
- Oulun Yliopisto, Oulu, Finland
- Servizo Galego De Saude, Santiago de Compostela, Spain
- Stichting Lygature, Utrecht, Netherlands
- Universitair Medisch Centrum Utrecht, Utrecht, Netherlands
- Universitatsklinikum Erlangen, Erlangen, Germany
- University Of Leeds, Leeds, United Kingdom
- University Of Newcastle Upon Tyne, Newcastle upon Tyne, United Kingdom
Small and medium-sized enterprises (SMEs)
- Artialis SA, Liège (Sart-Tilman), Belgium
- Dynamic Metrics Limited, Luton, United Kingdom
- Nordic Bioscience Compound Development A/S, Herlev, Denmark
- Stichting Nationaal Reumafonds, Amsterdam, Netherlands
- Universite Paris Cite, Paris, France
Non EFPIA companies
- Immunodiagnostic Systems Holdings PLC, Boldon, United Kingdom
|Name||IHI funding in €|
|Academisch Ziekenhuis Leiden||712 510|
|Artialis SA||250 000|
|Assistance Publique Hopitaux De Paris||141 050|
|Centre National De La Recherche Scientifique Cnrs||23 000|
|Diakonhjemmet Sykehus As||179 540|
|Dynamic Metrics Limited||185 000|
|Friedrich-Alexander-Universitaet Erlangen-Nuernberg||125 000|
|Hemics B.V. (left the project)||180 000|
|Lunds Universitet||179 000|
|Medizinische Universitaet Wien (left the project)||49 000|
|Nordic Bioscience Compound Development A/S||76 000|
|Oulun Yliopisto||214 000|
|Servizo Galego De Saude||464 000|
|Stichting Lygature||651 000|
|Stichting Nationaal Reumafonds||32 105|
|Universitair Medisch Centrum Utrecht||3 133 262|
|Universitatsklinikum Erlangen||35 000|
|University Of Leeds||150 000|
|University Of Newcastle Upon Tyne||585 000|
|University Of Surrey (left the project)||133 533|
|Name||Funding in €|
|Universite Paris Cite||2 000|
|Total Cost||7 500 000|