Current Studies

Updates on the Lupus Interactive Navigator (LIN):

The preliminary results of the qualitative analysis of the LIN focus groups and online surveys were presented at the 2012 CaNIOS Annual General meeting. The four main themes resulted from the focus groups’ analysis are the following:

Theme 1: Lupus consumers need lupus-tailored information;

Theme 2: Active health care system barriers in Lupus care;

Theme 3: Facilitators of Lupus consumer engagement in their care;

Theme 4: Lupus-accommodating lifestyle choices promote better control over disease activity. 

The LIN online surveys were distributed to 3119 people living with lupus (group 1), 517 rheumatologists (group 2) and 226 Allied Health Professionals (group 3) by respectively Lupus Canada, the Canadian Rheumatology Association, the Arthritis Health Profession Association. 

22 % of group 1, 19% of group 2 and 33% of group 3 responded to the LIN online surveys.

On October 15th, 2012, there was a stakeholder meeting in Montreal to discuss the development of the LIN. There were the representatives from the Canadian Rheumatology Association, Lupus Canada, consumers, rheumatologist, psychologist, nurse; other research staff with our partners Jack Digital Productions attended the meeting. At the end of November, there will be a conference call meeting to discuss the table of contents of the LIN with various stakeholders such as the Arthritis Society, Lupus Canada, the Canadian Scleroderma Research Group, the Canadian Rheumatology Association, and the Canadian Network for Improved Outcomes in Systemic Lupus Erythematosus.  Consumers will be invited to test and validate the LIN as soon as it is ready.

Empowering Patients as Active Partners in Their Care:  Lupus Interactive Navigator (LIN)

With CIHR Partnership in Health System Improvement grant, our team are working in close collaboration with our partner Jack Digital Productions (JDP) Inc., who is specializing in interactive educational material, to develop the Lupus Interactive Navigator (LIN). 

The principal goal of the LIN is to support providers in the delivery of person-centred care and engage patients as partners in their care and ongoing wellness.  

Between March and July, we collected data through focus groups held across Canada and web surveys. Participants were patients with lupus, rheumatologists, and Allied Health Professionals. Qualitative analyses were performed to determine the most helpful information, support resources, and features that should be included into the LIN. 

 

Innovate Lupus 

CaNIOS with the collaboration of Centre for Innovation in Complex Care (CICC) work at the design, implementation and evaluation of a provincial-based model of care to improve patient care and outcomes, and reduce the costs of managing patients with lupus. 

The goal of this project is to design, test, improve and disseminate a better approach to lupus care that can be implemented at the provincial level. We believe a system approach to lupus care will improve the quality of care patients receive, patient outcomes, and reduce overall system costs.

To do this, it is crucial that the Ministry of Health and Long-Term Care (MOHLTC) recognizes lupus care as a priority area. Implementation and evaluation of a small-scale clinical intervention will be paramount for communicating opportunity and success to MOHLTC.

The Role of Fatty Acid Composition in Disease Activity and Cardiovascular Disease in Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE), or lupus, is associated with many metabolic abnormalities causing damage to the blood vessels and thus a greater chance of heart disease compared to healthy people. There is no cure for lupus. Until now, the treatment of lupus has been limited to the use of drugs that control partially the disease and may be associated with unpleasant side effects.  However, the role of nutritional factors in SLE has been ignored.  Changing the fatty acids, or more simply fats, in the food that we eat can lead to differences in how our cells function and allow the production of better fats – thus opposing the effects of bad fats that can be modified by the disease processes of lupus.  For example, omega-3 fatty acids obtained from fish, a good fat, is shown to have heart-protective effects. Also, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are the two major fats that are in the cell membrane, or envelope of the cell.  The PC: PE ratio and their composition play an important role in maintaining cell functions. These factors have not been studied in SLE.  The project allows us to investigate in a study whether the nature of blood fats are associated and can predict SLE disease activity or damage and blood vessel abnormalities. SLE patients are particularly at risk of heart disease, bone disease, kidney disease and cancer. If we confirm associations between blood composition of fats and SLE disease outcomes, this may lead to better prevention and treatment through new dietary recommendations adapted to people with lupus.

The e-LHP: Dissemination of the Lupus Health Passport

This funding application is to supplement the knowledge transfer and exchange activity of the ongoing CIHR-funded study “Health Improvement and Prevention Program” (HIPP). HIPP is a randomized controlled trial that involves a behavioral intervention, and tests whether patients with lupus benefit from a behavioral intervention to increase knowledge of the disease and implement prevention strategies.  In HIPP, these patients learn ways to improve their coping skills, and to decrease their risk for cardiovascular disease and osteoporosis. A tool developed to monitor the program’s complex awareness, treatment adherence, and wellness promotion strategy, is a spiral bound hard copy document called the Lupus Health Passport (LHP).  The LHP is designed to empower patients to be informed and encourages them to be pro-active in their disease management.  Patients gain more knowledge of their disease, become less anxious, are in better control of their health outcomes, and cope better with their illness. The impact of the KTE process through the LHP has been very positive.  As HIPP is nearing completion, the passport is now ready for more widespread dissemination in other lupus clinics, and in the community. A web-based format, the e-LHP is therefore more economical, easier to maintain over time, more accessible and scalable to a larger number of consumers.  The objective of the project is to transpose the paper-based LHP into a e-LHP with a partner that has pioneered patient-centered disease management and web-based interactive programs in oncology. Patients will then be invited to participate in the development of the passport and in a usability exercise so they can provide feedback from the outset. We have enlisted the support of patient advocates and lupus provincial organizations who will help us with the dissemination of information in their support groups

Ongoing Research Projects

Lupus Nephritis New Emerging Team (LuNNET)  

LuNNET is now in its fifth year of operation with a total of 242 patients.  This study is divided into 4 cohorts. 

Cohort 1:

Renal biopsies from a retrospective cohort of 244 patients with Lupus (archived at UHN) have been re-scored by 2 independent pathologists using the new ISN/RPS classification of lupus nephritis. This study has also linked the ISN/RPS class of lupus nephritis and activity and chronicity indices to outcomes in lupus as well as association of vascular abnormalities on kidney biopsy and clinical manifestations and outcome in lupus. Expression of 45 genes on TLDA cards from 97 samples from renal biopsies from patients with lupus nephritis has also been analyzed.

Cohort 2:

This is an intensively followed cohort consisting of patients with and without Lupus Nephritis who were newly diagnosed or had active disease at the time of enrollment.  We have close to 100 patients in this cohort that are followed quarterly for the first 3 years and annually for an additional 2 years.  Clinical data are collected and blood (plasma, serum) and urine samples are stored for analysis of several biomarkers and genetic studies.   

Cohort 3:

This is a less intensively followed cohort in which clinical data is collected annually for 5 years from patients with or without lupus nephritis who had active/or inactive disease at the time of enrollment.  Blood and urine samples have been collected and stored at baseline and year one for analysis of several biomarkers and genetic studies.

Cohort 4:                                                             

A triad of blood, urine and tissue biopsies has been collected from 35 patients with Lupus Nephritis that required a renal biopsy procedure. Clinical data is also available on these patients. Longitudinal follow-up (up to 6 months) are available on 25 of these patients. Clinical data collected includes medications and disease activity measures.  Environmental exposures, data on quality of life and health care resource utilization have also been collected from patients in Cohorts 2 and 3.

Lupus Clinical Trials Consortium (LCTC) Data Registry

The registry is a prospective, observational study of patients with SLE sponsored by the Lupus Clinical Trials Consortium, Inc. (LCTC), a non-profit organization with a mission of helping to improve quality of life for lupus patients.  The objectives of the data registry is to (1) describe the natural history and clinical course of SLE including SLE damage, and (2) to describe the SLE treatments and the magnitude, duration, and quality of treatment responses, and to determine factors most predictive of these clinical responses.  Then, registry participants will be followed for up to five years from enrollment or until the registry ends or a participant discontinues participation.

The Health Improvement and Prevention Program (HIPP)

HIPP Study Lay Summary: Systemic lupus erythematosus (SLE) is a chronic disease in which a person's immune system attacks their own body organs. Controlling SLE is difficult because there are many symptoms that differ from person to person. Both SLE and the drugs used to treat it may lead to premature cardiovascular disease or osteoporosis. In addition, coping with having SLE can be very stressful. In our study, we are testing whether persons with SLE benefit from our Health Improvement and Prevention Program (HIPP). In HIPP, these persons will learn ways both to improve their coping skills and knowledge of SLE, and to decrease their risk for cardiovascular disease and osteoporosis. They will do this by working with a nurse who tailors a coping and risk-reduction program to fit each person's needs. Half of the persons will begin HIPP as soon as they enter the study (HIPP Now). The other half will receive their usual care for one year after study entry, but will begin HIPP in the second year (HIPP Later). At the end of the study we will compare the two groups to determine if increasing awareness of SLE and health behaviors improves general health, coping skills, and risk for cardiovascular disease or osteoporosis in persons with SLE.
 
Primary and Secondary objectives:
•To improve health status, decrease cardiovascular risk and improve endothelial function in persons with SLE compared to usual care. 
•To improve bone health behaviors and prevent decrease in bone mineral density.
•To improve adherence to treatments.
•To help persons with Lupus move toward wellness by increasing knowledge.
•To show that HIPP is cost effective and could become standard care. Follow ups
•Duration: 2 years
•Patients are seen yearly on average, more often if aggressive risk reduction is required
•Patients are followed by phone monthly
•Questionnaires are mailed Study Design:
•Randomized prospective study of HIPP compared to usual care, patients will be crossed over at 12 months
•Data will be collected for 24 months.
•Demographic, health status, cost, SLE knowledge, coping, cardiovascular and osteoporosis information will be collected. •All patients will undergo clinical evaluation to measure disease activity,
•All patients have Bone Mineral Density (BMD) Tests every 2 years or yearly if on prednisone
•All patients undergo ‘Flow Mediated Dilatation’. (FMD) yearly while participating in the study
•HIPP Now patients will attend 4 knowledge sessions, these sessions are given by experts in their fields, covering SLE, coping with chronic disease, cardiovascular disease in Lupus, bone health in Lupus.
•All HIPP Now patients in Toronto are seen by cardiologist for initial assessment
•HIPP Now patients will be followed by nurse coordinator and receive an individualized risk assessment for coronary artery disease.
•Telephone follow-up, smoking cessation counseling and those found at risk, stress reduction (Mindfulness Based Stress Reduction) and or bone health program will be provided.
•HIPP now patients will attend Cardiac Rehabilitation Program at TWH or receive a home exercise program with regular telephone follow-up
•All HIPP Now patients receive a Lupus Health Passport, a detailed diary covering medication history, blood and urine results, personal treatment plans, history of previous hospital admissions and clinic visits. Passport is updated every 3 months and results discussed with patient. Inclusion Criteria:
•SLE according to the American College of Rheumatology (ACR) criteria
•Female, 18 years or older
•Must read and write French or English Exclusion Criteria:
•Myocardial Infarction (MI) – heart attack
•Transient Ischemic Attack (TIA) – mini stroke
•Cerebrovascular accident (CVA) - stroke
•Other arterial occlusion, peripheral vascular disease (PVD) - blood clot in artery / vein
•Osteoporosis with fracture
•Pregnant
•Active cancer
 

Lupus Health Passport (LHP)

During the initial administration of HIPP to lupus patients, it became evident and necessary that a tool summarizing their disease profile, blood test results, past and current medications, their treatment plan, annual examinations and contact information of their many health care providers would be important. HIPP then developed the personalized Lupus Health Passport, a small spiral bound, pocket-sized booklet measuring 7 x 4 inches, and containing general information on lupus, cardiovascular disease (CVD) prevention, osteoporosis prevention, customized information about patient’s specific risks for CVD and osteoporosis, medication history, vaccination history, diet and exercise advise, upcoming visits, past hospitalization record and reason why, blood and urine test results.  All this information is updated at each clinic visit by a nurse case manager. The French-Canadian, Spanish and the pediatric versions of the Lupus Health Passport were also developed.  Lupus patients involved in the study reported that gaining more knowledge of their disease translated into less anxiety and that they are in better control of their health outcomes because they can monitor their test results in a manner that provides them with more knowledge to cope with their illness.  Dr. Fortin has recently received a Knowledge transfer supplement CIHR/CAN grant to bring the lupus passport onto a Web platform.  He is collaborating with the Jack Digital Productions Inc. to adapt the LHP and to develop jointly a Lupus Interactive Navigator.  This would be a clear application of his ultimate career goal, which is to improve patient’s outcomes and quality of life not only in academic centers but widely into the community. 

Past Projects

Improving Transition Readiness and OoL with a Pediatric Health Passport

Childhood-onset Systemic Lupus Erythematosus (cSLE) is a chronic incurable condition that requires life-long care.  Optimizing self-management skills, self efficacy, and coping is necessary to maximizing health outcome and quality of life (QoL).  The study aims to improve these skills through the use of a pediatric Lupus Health Passport (pLHP), a pocket-sized notebook developed to manage health-related information, the pLHP permits tracking of disease manifestations, medications, lab results, physician visits, health maintenance tasks, and provides a transition readiness check-list. 

The Role of Thrombophilic Factors in Person with Systemic Lupus Erythematosus (ThromboFIL) 

The ThromboFIL study has now completed its phase 1.  During Phase 1 of ThromboFIL, we recruited 359 patients and documented 40 new thrombovascular events (TE) in 27 individuals.  Part of the project was to augment the original ThromboFIL cohort by adding cases (patients with TE) and matched controls from the Montreal and Toronto Lupus clinics on whom biobanked samples were available. Then, new vascular events were captured at baseline and annual visits as part of the collection protocols at both centers.  Also, lupus patients from Toronto Lupus clinic were selected according to pre-specified criteria to perform in vivo and in vitro endothelial sub-studies.  Of these, we further selected patients with stored blood samples pre- and post-TE for the proteomic sub-studies.  The project allowed us to link the in vivo and in vitro endothelial substudies with the proteomic output, and seek new interesting associations between endothelial cell functions, proteomic signatures, and TE.

Genetic and Environmental Factors in Systemic Lupus Erythematosus (GenES Study)

GenES research program works to identify genes, environmental factors, and gene-environment interactions that influence the risk for SLE. 

In phase 1 of GenES, we collected and phenotyped 259 SLE cases, together with their parents, siblings, and 262 category-matched age, gender and geographic area random controls. We expanded phenotypic characterization of our sample beyond the traditional ACR classification for SLE to include cellular markers of B and T cells and serology.  Our results show that many cellular and serological phenotypes (ANA and other autoantibodies) are: (1) significantly different between cases and controls (2) different in the first-degree relatives of lupus patients compared to controls, and (3) significantly heritable.  In addition, we have identified and replicated a number of genetic variations associated with lupus and shown an association between several of these genetic variations and the serological and cellular traits in lupus patients and their first-degree relatives.  We have also collaborated on the replication phase of the 3rd published genome-wide association (GWA) study of SLE that identified a novel susceptibility gene.

In the phase two of this study, we are collaborating more than 800 extensively phenotyped SLE patients to an international GWA study coordinated by Dr. Tim Vyse, London UK .  Our interest in this collaboration is to use the GWA study data to identify novel genetic loci associated not only with global lupus phenotype, but also numerous lupus-specific serological and cellular measures as well as clinical sub-phenotypes.

The 1000 Canadian Faces of Lupus

Initially funded by The Arthritis Society (TAS), the 1000 Canadian Faces of Lupus Study aims to describe SLE in Canada, comparing manifestations in different ethnicities. Funding from TAS has been exhausted, but bridge funding support from Lupus Manitoba allowed the study to continue for several more months. The study is currently seeking further funds from the Canadian Arthritis Network (CAN), and had submitted a funding proposal to the Rapid Impact Platform Program (RIPP) for the June 2010 competition. 

To date, the study has collected data on 1849 SLE patients (above the target of 1000) capturing demographics, ethnicity, disease severity, activity, and damage, medications, health habits and comorbidities; studying adults and children at 14 sites with up to 4 years of longitudinal data. 

In the past five years, the group has published 4 manuscripts, one is now in press, and 5 published abstracts have resulted, including 3 podium presentations at national and international meetings. 

The papers published cover several areas (1) ethnic differences in SLE (2) health care barriers in the 1000 Faces cohort even in optimal setting (3) late onset SLE (age >50, 10% of our cohort) (4) work disability; 19% are work disabled. (5) pulmonary involvement in lupus (6) effect of different environments on 2 populations, comparison between Canadian and Hong Kong Chinese patients.

Lymphoma Risk: A Consequence of Immune Suppression or Stimulation?

The primary objective of this study is to determine if SLE disease activity is associated with lymphoma development. The second objective was to determine if lymphomas in SLE differ in terms of specific histological features compared to lymphoma cases in the general population. The significance of the project is that given the rapid emergence of novel agents which may more effectively control immune stimulation, but further perturb immune surveillance, our research will be crucial in understanding how immune dysregulation influences cancer risk in autoimmune diseases such as SLE. It is hoped that our research will help identify patients at highest risk for lymphoma and provide therapeutic guidance.

SMILE: Study of Methorotrexate in Lupus Erythematosus

The general aim of the multi-centered randomized placebo-controlled trial of low dose intermittent methotrexate with folic acid is to establish whether methotrexate shows efficacy and safety in controlling disease activity is systemic lupus erythematosus and preventing flares or development of end-organ damage. A second aim will be to document whether methotrexate has a significant steroid sparing effect in systemic lupus erythematosus. A third aim will be to measure the toxicity and cost of methotrexate with folic acid and to perform cost-effectiveness and cost-utility analyses.