Norwegian systemic connective tissue disease and vasculitis registry (NOSVAR)
NOSVAR is a registry owned and funded by Oslo University Hospital (OUH ) used for research and quality assurance on rheumatic connective tissue diseases and vasculitis. The registry is approved by relevant authorities and based on the written consent of the patients. In an associated «biobank» blood and serum samples are stored. The registry has no ties to the pharmaceutical industry, information technology companies or other commercial operators.
PURPOSE / OBJECTIVE
NOSVARs purpose is to systematize experiences with rare systemic connective tissue diseases and vasculitis, evaluate the results and publish them so that new knowledge reach patients, clinicians and researchers.
– «To get an overview of what we do, we must register»
– «Registers provide a basis for improving what we do»
Further, NOSVAR shall contribute to cooperation between patients, the Norwegian academic community and researchers and to develop an international professional network.
The start. Professor Øystein Førre took the initiative in 1998 and founded the «Registry of autoimmune connective tissue disease”. The register also included vasculitis. Torhild Garen has been registry consultant since its inception and provides continuous operation and key input. On the ward, Kari Fresjar contributes to most complete inclusions.
In 2002 registration reorganized under the leadership of Professor Jan Tore Gran. Initially it was envisaged comprehensive registrations by including epidemiological parameters and regularly monitoring. This resulted in a disproportionate amount of work with the patient inclusions and controls, and thus incomplete data. Since 2002, registrations are performed only once, with the exception of systemic sclerosis (see below). The registered parameters are limited mainly to parameters for classification of diagnosis and physical function.
Since 2008, PhD Øyvind Palm has been registry manager. Besides focusing on most complete records have facilitating research tasks and publication of results been a target.
NOSVAR. The name of the registry was changed in 2011 to NOSVAR (Norwegian systemic vasculitis and connective tissue disease registry). The name change was necessary due to publications in English literature: Norwegian systemic connective tissue disease and vasculitis registry (NOSVAR).
In line with the reorganization of hospital structure, the costs the registry been covered by Oslo Sanitetsforenings Rheumatism Hospital (OSR), The National Hospital (Rikshospitalet) and currently, Oslo University Hospital (OUH).
Current. By 2017 more than 3.500 patients has been included, making NOSVAR a large registry even in an international context.
ETHICS AND DATA SECURITY
The registry has since 1998 had the approval of the Norwegian Social Science Data Inspectorate, and with license valid until 2028. All registrations are based on «informed consent», which means that each patient receive oral and written information about the registry and the “biobank” before any inclusion. It is possible to withdraw from the register anytime.
For register-based research, studies require Regional Ethics Committee approvals before starting. Whatever, personally identifiable patient data are not published, so no individual patients is recognized by publications or other presentations. Privacy Ombudsman at OUH (on behalf of the Data Inspectorate) has evaluated and approved safety during storage and handling of data. The name change to NOSVAR in 2011 was made in accordance with the Ethics Committee.
DISEASES AND STRUCTURE
The main diagnostic groups and number (n) of included patients in NOSVAR are shown below*:
Vasculitis of small blood vessels
- GPA (Wegener’s granulomatosis) & other ANCA-vasculitis n= 274
Vasculitis of major blood vessels
- Behcet disease n= 76
Connective Tissue Diseases
- SLE n=727
- Sjögren’s Syndrome n=549
- Systemic Sclerosis / scleroderma n=605
- Myositis n=310
- MCTD / Mixed connective tissue disease n=179
.*Reference: Annual NOSVAR 2017
Systemic sclerosis (scleroderma)
Systemic sclerosis has in recent years been a disease of our priority. NOSVAR receives annual registrations from the rheumatology ward. Registrations of systemic sclerosis are more comprehensive and cover systemic medication, organ involvement, quality of life and physical function of different organ systems. The data forms the basis for future prospective studies.
The establishment also of biobank in 2005 was prescient. Most included patients have accepted that blood and serum can be stored. The “biobank” is important and has in recent years contributed to important, published data for research and quality improvement. More details are provided in the annual reports (in Norwegian language) from 2011 to 2017.
The patients effort is needed. Patients, who kindly register are the basis for all research and quality assurance in NOSVAR. Interest in the use of NOSVAR data has been great in recent years. Rheumatologists, fellows and other researchers make registrations, calculations and publish the results. Data from NOSVAR also contributes to improved quality information given by doctors, nurses and other health workers to the patients. Along with the patients, we obtain new knowledge about rheumatic connective tissue diseases and vasculitis.
Collaboration with other rheumatologic departments. Scientific, internationally published manuscripts have been prepared in cooperation with all Norwegian rheumatology departments, represented at the author lists.
Previously inclusions in the registry have been made by the rheumatologic departments in Bodø, Moss, Førde, MH / Sandvika, Ålesund, Drammen, Lillehammer, Kongsvinger, Kristiansand in addition to OUH, Rikshospitalet, which is responsible for the registry. A new electronic registration solution has been long in coming, which is why OUH, Rikshospitalet has registered alone since 2008. Recent efforts has, however, been taken in order to initiate a closer cooperation between the academic communities.
Internally teamwork. Within OUH, joint projects with the Institute of Immunology and Department of Internal Medicine research are established to researching disease mechanisms. Shared publications with the departments of lung diseases, kidney diseases, cardiovascular diseases, immunology, physiotherapy, pathology and radiology have been realized.
International collaboration is often necessary to achieve good results by research on rare diseases. Cooperation also results into networking, which may be useful in clinical management of rare, specific diseases too.
- EUSTAR is a European research collaboration on systemic sclerosis. In 2015 NOSVAR contributed with data published in five manuscripts in the Annals of Rheumatic Diseases (ARD), which is considered the world’s best journal for Rheumatology
Genetics (Mapping of hereditary factors that predispose to diseases)
- Genetic factors disposing for systemic sclerosis and its complications are since 2010 explored in collaboration with an international research team in Spain (including the Spanish Scleroderma Group), led by Professor Javier Martin
- Giant cell arteritis / Temporal arteritis is genetically mapped in collaboration with the group of Professor Miguel A Gonzalez-Gay in Spain
- A new study on GPA / Wegener’s granulomatosis is underway in cooperation with Uppsala University and other Swedish center
- EuMyoNet: Cooperation on patients with myositis
As a part of the Department of Rheumatology’s research in OUH, NOSVAR data are used by PhD fellows, researching new aspects of the systemic connective tissue diseases and vasculitis. NOSVAR data has so far been used in more than 70 publications in international peer reviewed journals (per 2018).
PhD theses (doctoral theses), which have used data from NOSVAR:
- MD Ragnar Gunnarsson, PhD work on MCTD in 2013
- Dentist Tone Berge, PhD degree in 2014 on Sjögren’s syndrome
- MD Lara Bossini-Castillo, Spanish PhD in 2014 on the basis of genetic analysis of systemic sclerosis
- MD Anna Hoffmann -Vold, PhD degree in 2014 on systemic sclerosis
- MD Karoline Lerang, Systemic lupus, 2015
- MD Cecile Dobloug, Myositis, 2015
- MD Helena Andersson, Antisynthetase syndrom, 2017 (scheduled August)
- MD Birgir Gudbrandsson, Takayasu arteritis 2017 (scheduled Noveber)
Systemic lupus (SLE)
- SLE is researched by fellow MD Karoline Lerang. She has estimated the incidence of SLE and the disease severity. She has also shown that there are differences in diagnosis and treatment, depending on whether the patients are managed by rheumatologists or other specialists. Karoline Lerang defened her PhD degree sucessfully in 2015.
Systemic sclerosis (Scleroderma)
- Systemic sclerosis is priority for NOSVAR. MD Anna Maria Hoffmann-Vold defended her PhD work in 2014. Among the published manuscripts are Norwegian data for incidence and survival in systemic sclerosis
- Genetic associations have been investigated in collaboration with MD Lara Bossini-Castillo and Professor Javier Martin in Spain. NOSVAR data contributed to Lara Bossini-Castillo’s PhD degree on genetics of systemic sclerosis in 2014
- NOSVAR-data are also used in the European research network European Scleroderma Trial and Research Group (Eustar). The network focuses on epidemiology and new therapies
- Mixed connective tissue disease (MCTD) in Norway has been described in the PhD work of PhD Ragnar Gunnarsson in 2013
- Fellow Silje Reiseter is now bringing this topic further in a new PhD work (the NorMCTD project)
- Sjögren’s syndrome has been investigated in collaboration with the Faculty of Dentistry at the University of Oslo and PhD Tone Berge Enger and Professor Janicke C Liaaen Jensen. The group has recently shown that Sjögren’s syndrome affects oral health and quality of life significantly and that more than 20% of the patients have lung involvement. A new PhD- and a post-Doc work started 2015.
Giant Cell Arteritis / arteritis temporalis
- A large genetic research program is being performed in collaboration with the research group of Professor Miguel A Gonzales Gay in Spain
- We have also implemented a quality assurance study, evaluating the optimal dosage of cortisone (prednisone) in the treatment of the disease. The results described in Best Practice (professional dialogue between specialists) in May (No. 19) in 2014. As a consequence of the results, the Department of Rheumatology OUH, has changed the treatment regime
- Takaysu arteritis is studied by fellow MD Birgir Gudbrandsson in a PhD work. Incidence, prevalence and disease manifestations og the disease have been published. Morover, data on pregnancy outcomes and complications have been estimated and publised.
Granulomatosis with Polyangiitis / Wegener’s granulomatosis
- The genetics of the disease are explored in a multicenter collaboration with Swedish university clinics. The project is led by PhD Johanna Dahlquist at the University of Uppsala
- A clinical PhD work has been initiated
Myositis and antisyntetase syndrome
- Myositis and antisyntetase syndrome are studied by PhD fellows MD Cecilie Dobloug and MD Helena Andersson, respectively. Cecilie Dobloug defended her PhD work successfully in 2015.
- NOSVAR delivers data to EuMyoNet, a research network funded by the European Science Foundation.
- Patients are signaling willingness to support the work of NOSVAR also in the future
- Young, successful scientists and from in-and outside OUH, Rikshospitalet are expected to publish several important results in the coming years
- The external interests in NOSVAR are growing
- Collaboration with various research groups at home and abroad is increasing and expected bring new registry-based knowledge
- Oslo University Hospital has indicated further investments in NOSVAR
- Currently, only financial limitations and our own capacity for work and creativity that are limiting factors for further developments of NOSVAR
ARE YOU A PATIENT AND WANT TO CONTRIBUTE TO NOSVAR?
Inclusions are currently done only by doctors at The Department of Rheumatology, Oslo University Hospital, Rikshospitalet. It is a necessary that the diagnosis is absolute, and that you are referred (by a doctor) or already patient at the section.
DO YOU WANT TO SUPPORT NOSVAR WITH FINANCIAL FUNDING?
Achieving public funding for studies of such rare diseases as systemic connective tissue disease and vasculitis is difficult. We have unrealized ideas for interesting future studies and skilled fellows waiting for essential financial support. All projects will be integrated in the research strategy of Department of Rheumatology at Oslo University Hospital and funding must be in accordance with the policy of the hospitals standards.
Please make contact with Department of Rheumatology, Oslo University Hospital, Postbox 4950 Nydalen, N-0424 Oslo, Norway.
ADMINISTRATION AND FUNDING
Leader: Rheumatologist PhD Øyvind Palm
Coordinator: Torhild Garen
Funding: Public funds
Bindings to commercial businesses: None
Data Processing Manager: Oslo University Hospital (OUH)