Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
UNKNOWN
Total Enrollment
3700 participants
Study Classification
OBSERVATIONAL
Study Start Date
2018-05-09
Study Completion Date
2025-03-31
Brief Summary
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A Systemic lupus erythematosus, SLE is disease in which immune system is over-active causing inflammation in joints skin or any organ system. There are many areas where better approaches in SLE could improve outcomes. One example relates to hydroxychloroquine (HCQ) key drug which can reduce risk of serious disease flares. There are increasing concerns about eye damage main side effect with long-term use of HCQ. At present investigators cannot precisely predict which SLE patient is most likely to flare once HCQ is tapered. It is not clear what drives risk of eye damage. Investigators' study will fill these knowledge gaps. Investigators' hypothesis is that baseline demographic and clinical factors are associated with risk of SLE flare after HCQ taper/discontinuation and with risk of retinal toxicity in all HCQ exposed patients. Research will link and analyze data on 3700 SLE patients across Canada.
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Detailed Description
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B OBJECTIVES B1 To evaluate in SLE patients who lower but do not discontinue HCQ factors associated with flare (significant increase in disease activity, augmentation of therapy or hospitalization for SLE).
B2 To determine in SLE patients who discontinue HCQ factors associated with flare (significant increase in disease activity, therapy augmentation or hospitalization for SLE).
B3 To evaluate temporal relationship between HCQ use and retinal toxicity in SLE patients and how this may be associated with demographic and clinical factors.
B4 To assess SLE patient preferences for HCQ therapy and how preferences are associated with demographic and clinical factors.
B5 To evaluate temporal relationship between antimalarial use and other forms of toxicity in SLE patients and how this may be associated with demographic and clinical factors.
Team members have prospectively followed cohorts \> 3700 adult SLE patients (90% HCQ exposed) with collected and harmonized data on demographics and clinical factors. Team members (Bernatsky Abrahamowicz Fortin Hazlewood) are founding members of CAN-AIM CIHR-funded Drug Safety and Effectiveness Network team.
Members have history of working with patients as research partners (Bartlett Li Bernatsky Fortin Hazlewood). Investigators' ties to stakeholders including patient research partners and Lupus Canada facilitates knowledge translation.
METHODS C1 Cohorts: Investigators will use existing data on adult SLE patients enrolled into study cohorts in Montreal Quebec Halifax Winnipeg Calgary and Toronto.
Investigators are members of national (Canadian Network for Improved Outcomes in SLE CaNIOS) and/or international (Systemic Lupus International Collaborating Clinics SLICC) research networks. CaNIOS and SLICC have worked decades on harmonized approach to prospectively-collected. Cohorts enroll unselected patients when they present to clinic. At annual assessments data are collected on drugs disease activity organ damage etc C2.1 Patient selection for Objective 1: At baseline and follow up visits records are made of patient HCQ doses. Starting with first visit with HCQ exposure investigators will determine how many patients are recorded as receiving lower dose or discontinuing HCQ at follow-up visit. Patients identified as having lowered HCQ dose will form sub-cohort for time-to-event (survival) analyses. Investigators will evaluate only first-ever lowering of HCQ. Analysis will evaluate patients from time zero (annual visit at which lower HCQ dose was recorded) to assess combined outcome of earliest of a) increase in SLEDAI-2K of at least 4 points and/or b) hospitalization for SLE and/or c) augmented SLE therapy defined as increase in HCQ or new start or increase in corticosteroids or other immunosuppressant. In addition to accepted minimal clinically significant SLEDAI-2K change investigators include drug changes and SLE-related hospitalizations.
Patients studied in Objective 1 will be right censored if HCQ is discontinued completely; these will enter into analyses for Objective 2. Otherwise patients will be followed until outcome of interest or end of study.
C2.3 Subject selection for Objective 2 Analyses will be similarly conducted but time zero will begin when individual discontinues HCQ. Objective 1 and 2 analyses conducted separately; patients who have HCQ dose lowered but then discontinued will be in analyses for Objective 1 up to point of discontinuation then patients will be right censored for Objective 1. Subjects are able to contribute data (from the point of HCQ discontinuation) to analyses for Objective 2. Patient can contribute to analyses for one or both objectives and contributing to Objective 3. If not right-censored patients will be followed until outcome of interest or end of study.
C2.3 Subject selection for Objective 3 Outcome is retinal toxicity assessed in HCQ-exposed patients from time of first visit with HCQ exposure up to time of retinal toxicity documentation or end of study for patients without outcome. Exposure to CQ (relatively uncommon drug exposure) is also risk factor for retinal toxicity but essentially patients exposed to CQ will have prior exposure to HCQ.
C3 Demographic and clinical factors C3.1 Variables assessed include sex age at SLE onset and race/ethnicity. Analyses adjusted for education as education can alter adherence.
C3.2 Clinical factors for multivariable analyses include smoking BMI baseline disease activity malignancy data and renal damage. Baseline refers to time zero. Renal damage is captured with SLICC Damage Index measuring accumulated damage. Baseline disease activity measured by internationally used SLEDAI-2K reliable validated widely used global score index.Investigators will model time-varying drug exposures with step-up approach initially with baseline use ie current, recent, ever or total past dose. Investigators use sophisticated and novel weighted cumulative dose modelling to flexibly represent exposures accumulated by individual subjects up to given time-point corresponding to each risk set for time-to-event analyses. In multivariable analyses approach will allow investigators to explore how risk of retinal toxicity may depend on details of past HCQ exposure including not only total cumulative dose but temporal pattern of doses at various time in past with differential weights for early versus later exposures.
C4 Outcome assessment: SLEDAI-2K and drugs are recorded. SLICC Damage Index has item for retinal damage and updated yearly.
C5 Model development: Investigators will perform multivariable time-to-event analyses in patients who lower or discontinue HCQ. Data for outcomes are available longitudinally at annual visit with actual dates only available for addition/increase in corticosteroid or SLE hospitalization. For other outcomes investigators will deal with interval-censored data familiar issue in pharmacoepidemiology.
Models include baseline demographics education BMI SLE duration SLEDAI-2K renal damage and medications. Simplistic survival analyses often assume linear effects of continuous covariates and impose conventional proportional hazards (PH) assumptions; investigators know that prognostic factors may have time-dependent and/or nonlinear effects that violate assumptions. Investigators will account for this. Methods account for possible changes in hazard ratio over time (violation of the PH) and allow estimation of relative risks (hazard ratios) and actual probabilities of event of interest occurring.
Similar approach will be used for Objective 3 in time-to-event analyses of retinal toxicity in patients exposed to HCQ.
Competing risks occur when subjects can experience one or more events that may compete with outcome of interest and hinder observation of event of interest or modify chances for event to occur. In sensitivity analyses investigators use competing risks models to simultaneously estimate associations between HCQ exposures and hazards of competing event.
D POWER/SAMPLE CALCULATIONS D1 Power calculations for multivariate models Combined cohorts include over 3300 patients have exposed to HCQ. Patients have had lowering of dose 45% or discontinuation of HCQ during their follow-up. Power calculations are based on available data suggesting that 45%-60% of SLE patients may flare over ten years of follow-up.
For baseline SLEDAI-2K assuming 35% of patients score less than 3 investigators would have 90% power to detect unadjusted HR of 1.30 and adjusted HR of 1.37 for variable. Assuming 20% of patients have renal damage investigators will have 90% power to detect an unadjusted HR of 1.37 and an adjusted HR of 1.45 for variable.
E KNOWLEDGE TRANSLATION activities are informed by history of partnerships between investigators and knowledge-users directed by Dr. Linda Li Canada Research Chair in Patient-Oriented KT and Director of Knowledge Translation Research Program at UBC's Arthritis Research Centre of Canada.
E1 Integrated KT Proposal developed in consultation patients from Lupus Canada patients Canadian Alliance of Patients with Arthritis (CAPA) and Singer Family Fund for Lupus Research. Wendy Singer (providing expertise health information dissemination and provides insight of SLE patient who has been affected by HCQ-induced retinal toxicity) will assist with educational tool developments. Co-PI Dr. Bartlett has over decade of work with patient partners through OMERACT (Outcome Measures in Rheumatology) and other organizations to help disseminate findings patient communities.
E2 Dissemination via MyLupusGuide: Data on HCQ from current study will be incorporated into MyLupusGuide web-based patient-centred health-management tool developed by Dr. Fortin in partnership with Jack Digital Productions CaNIOS Lupus Canada. Development validation/dissemination of current version funded by CIHR operating and dissemination grants.
E3 Clinicians and professional groups: Dr. Bernatsky is member of CRA Therapeutics Committee which advises CRA on policies related to drug use for rheumatic diseases. Group monitors information about adverse events related to drugs used in rheumatology including HCQ. Investigators submit abstracts to scientific meetings (American College of Rheumatology, European League Against Rheumatism, CRA meeting). Investigators will seek feedback on feasibility/approaches to integrate MyLupusGuide as gold standard for patient education tool concerning HCQ.
E4 Informing future guidelines: Team member Dr. S. Keeling has already produced Canadian SLE care guidelines (funded by the CIHR and endorsed by the CRA and CaNIOS) . In 2019, again mandated by these groups, Dr. Keeling will spearhead guidelines for SLE therapies.
E5 Health agency stakeholders: Investigators have connections Drug Safety and Effectiveness Network (DSEN) Health Canada's Marketed Health Product Directorate and Canadian Agency for Drugs and Technologies in Health (CADTH). Drs. Abrahamowicz and Bernatsky are co-leads DSEN-funded team.
B2 To determine in SLE patients who discontinue HCQ factors associated with flare (significant increase in disease activity, therapy augmentation or hospitalization for SLE).
B3 To evaluate temporal relationship between HCQ use and retinal toxicity in SLE patients and how this may be associated with demographic and clinical factors.
B4 To assess SLE patient preferences for HCQ therapy and how preferences are associated with demographic and clinical factors.
B5 To evaluate temporal relationship between antimalarial use and other forms of toxicity in SLE patients and how this may be associated with demographic and clinical factors.
Team members have prospectively followed cohorts \> 3700 adult SLE patients (90% HCQ exposed) with collected and harmonized data on demographics and clinical factors. Team members (Bernatsky Abrahamowicz Fortin Hazlewood) are founding members of CAN-AIM CIHR-funded Drug Safety and Effectiveness Network team.
Members have history of working with patients as research partners (Bartlett Li Bernatsky Fortin Hazlewood). Investigators' ties to stakeholders including patient research partners and Lupus Canada facilitates knowledge translation.
METHODS C1 Cohorts: Investigators will use existing data on adult SLE patients enrolled into study cohorts in Montreal Quebec Halifax Winnipeg Calgary and Toronto.
Investigators are members of national (Canadian Network for Improved Outcomes in SLE CaNIOS) and/or international (Systemic Lupus International Collaborating Clinics SLICC) research networks. CaNIOS and SLICC have worked decades on harmonized approach to prospectively-collected. Cohorts enroll unselected patients when they present to clinic. At annual assessments data are collected on drugs disease activity organ damage etc C2.1 Patient selection for Objective 1: At baseline and follow up visits records are made of patient HCQ doses. Starting with first visit with HCQ exposure investigators will determine how many patients are recorded as receiving lower dose or discontinuing HCQ at follow-up visit. Patients identified as having lowered HCQ dose will form sub-cohort for time-to-event (survival) analyses. Investigators will evaluate only first-ever lowering of HCQ. Analysis will evaluate patients from time zero (annual visit at which lower HCQ dose was recorded) to assess combined outcome of earliest of a) increase in SLEDAI-2K of at least 4 points and/or b) hospitalization for SLE and/or c) augmented SLE therapy defined as increase in HCQ or new start or increase in corticosteroids or other immunosuppressant. In addition to accepted minimal clinically significant SLEDAI-2K change investigators include drug changes and SLE-related hospitalizations.
Patients studied in Objective 1 will be right censored if HCQ is discontinued completely; these will enter into analyses for Objective 2. Otherwise patients will be followed until outcome of interest or end of study.
C2.3 Subject selection for Objective 2 Analyses will be similarly conducted but time zero will begin when individual discontinues HCQ. Objective 1 and 2 analyses conducted separately; patients who have HCQ dose lowered but then discontinued will be in analyses for Objective 1 up to point of discontinuation then patients will be right censored for Objective 1. Subjects are able to contribute data (from the point of HCQ discontinuation) to analyses for Objective 2. Patient can contribute to analyses for one or both objectives and contributing to Objective 3. If not right-censored patients will be followed until outcome of interest or end of study.
C2.3 Subject selection for Objective 3 Outcome is retinal toxicity assessed in HCQ-exposed patients from time of first visit with HCQ exposure up to time of retinal toxicity documentation or end of study for patients without outcome. Exposure to CQ (relatively uncommon drug exposure) is also risk factor for retinal toxicity but essentially patients exposed to CQ will have prior exposure to HCQ.
C3 Demographic and clinical factors C3.1 Variables assessed include sex age at SLE onset and race/ethnicity. Analyses adjusted for education as education can alter adherence.
C3.2 Clinical factors for multivariable analyses include smoking BMI baseline disease activity malignancy data and renal damage. Baseline refers to time zero. Renal damage is captured with SLICC Damage Index measuring accumulated damage. Baseline disease activity measured by internationally used SLEDAI-2K reliable validated widely used global score index.Investigators will model time-varying drug exposures with step-up approach initially with baseline use ie current, recent, ever or total past dose. Investigators use sophisticated and novel weighted cumulative dose modelling to flexibly represent exposures accumulated by individual subjects up to given time-point corresponding to each risk set for time-to-event analyses. In multivariable analyses approach will allow investigators to explore how risk of retinal toxicity may depend on details of past HCQ exposure including not only total cumulative dose but temporal pattern of doses at various time in past with differential weights for early versus later exposures.
C4 Outcome assessment: SLEDAI-2K and drugs are recorded. SLICC Damage Index has item for retinal damage and updated yearly.
C5 Model development: Investigators will perform multivariable time-to-event analyses in patients who lower or discontinue HCQ. Data for outcomes are available longitudinally at annual visit with actual dates only available for addition/increase in corticosteroid or SLE hospitalization. For other outcomes investigators will deal with interval-censored data familiar issue in pharmacoepidemiology.
Models include baseline demographics education BMI SLE duration SLEDAI-2K renal damage and medications. Simplistic survival analyses often assume linear effects of continuous covariates and impose conventional proportional hazards (PH) assumptions; investigators know that prognostic factors may have time-dependent and/or nonlinear effects that violate assumptions. Investigators will account for this. Methods account for possible changes in hazard ratio over time (violation of the PH) and allow estimation of relative risks (hazard ratios) and actual probabilities of event of interest occurring.
Similar approach will be used for Objective 3 in time-to-event analyses of retinal toxicity in patients exposed to HCQ.
Competing risks occur when subjects can experience one or more events that may compete with outcome of interest and hinder observation of event of interest or modify chances for event to occur. In sensitivity analyses investigators use competing risks models to simultaneously estimate associations between HCQ exposures and hazards of competing event.
D POWER/SAMPLE CALCULATIONS D1 Power calculations for multivariate models Combined cohorts include over 3300 patients have exposed to HCQ. Patients have had lowering of dose 45% or discontinuation of HCQ during their follow-up. Power calculations are based on available data suggesting that 45%-60% of SLE patients may flare over ten years of follow-up.
For baseline SLEDAI-2K assuming 35% of patients score less than 3 investigators would have 90% power to detect unadjusted HR of 1.30 and adjusted HR of 1.37 for variable. Assuming 20% of patients have renal damage investigators will have 90% power to detect an unadjusted HR of 1.37 and an adjusted HR of 1.45 for variable.
E KNOWLEDGE TRANSLATION activities are informed by history of partnerships between investigators and knowledge-users directed by Dr. Linda Li Canada Research Chair in Patient-Oriented KT and Director of Knowledge Translation Research Program at UBC's Arthritis Research Centre of Canada.
E1 Integrated KT Proposal developed in consultation patients from Lupus Canada patients Canadian Alliance of Patients with Arthritis (CAPA) and Singer Family Fund for Lupus Research. Wendy Singer (providing expertise health information dissemination and provides insight of SLE patient who has been affected by HCQ-induced retinal toxicity) will assist with educational tool developments. Co-PI Dr. Bartlett has over decade of work with patient partners through OMERACT (Outcome Measures in Rheumatology) and other organizations to help disseminate findings patient communities.
E2 Dissemination via MyLupusGuide: Data on HCQ from current study will be incorporated into MyLupusGuide web-based patient-centred health-management tool developed by Dr. Fortin in partnership with Jack Digital Productions CaNIOS Lupus Canada. Development validation/dissemination of current version funded by CIHR operating and dissemination grants.
E3 Clinicians and professional groups: Dr. Bernatsky is member of CRA Therapeutics Committee which advises CRA on policies related to drug use for rheumatic diseases. Group monitors information about adverse events related to drugs used in rheumatology including HCQ. Investigators submit abstracts to scientific meetings (American College of Rheumatology, European League Against Rheumatism, CRA meeting). Investigators will seek feedback on feasibility/approaches to integrate MyLupusGuide as gold standard for patient education tool concerning HCQ.
E4 Informing future guidelines: Team member Dr. S. Keeling has already produced Canadian SLE care guidelines (funded by the CIHR and endorsed by the CRA and CaNIOS) . In 2019, again mandated by these groups, Dr. Keeling will spearhead guidelines for SLE therapies.
E5 Health agency stakeholders: Investigators have connections Drug Safety and Effectiveness Network (DSEN) Health Canada's Marketed Health Product Directorate and Canadian Agency for Drugs and Technologies in Health (CADTH). Drs. Abrahamowicz and Bernatsky are co-leads DSEN-funded team.
Conditions
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Systemic Lupus Erythematosus
Study Design
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Observational Model Type
COHORT
Study Time Perspective
RETROSPECTIVE
Study Groups
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SLE Cohort
Investigators will use existing data collected on adult SLE patients enrolled into respective study cohorts from participating centers.
No interventions assigned to this group
Qualitative group
For the interviews, patients with SLE who are currently or have taken Hydroxychloroquine will be recruited from rheumatology clinics in Calgary and Montreal to participate in an interview and/or participate in a brief survey.
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
* Must be 18 years of age or over
* Must be diagnosed with Systemic Lupus Erythematosus (SLE)
* Must be exposed to hydroxychloroquine
* Must be enrolled at participating sites
* Must be diagnosed with Systemic Lupus Erythematosus (SLE)
* Must be exposed to hydroxychloroquine
* Must be enrolled at participating sites
Exclusion Criteria
* Under 18 years of age
* Not diagnosed with SLE
* Not exposed to hydroxychloroquine
* Not enrolled at participating sites
* Not diagnosed with SLE
* Not exposed to hydroxychloroquine
* Not enrolled at participating sites
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Laval University
OTHER
Sponsor Role
collaborator
University of British Columbia
OTHER
Sponsor Role
collaborator
University of Calgary
OTHER
Sponsor Role
collaborator
Dalhousie University
OTHER
Sponsor Role
collaborator
University of Manitoba
OTHER
Sponsor Role
collaborator
University of Toronto
OTHER
Sponsor Role
collaborator
University of Alberta
OTHER
Sponsor Role
collaborator
McGill University Health Centre/Research Institute of the McGill University Health Centre
OTHER
Sponsor Role
lead
Responsible Party
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Dr. Sasha Bernatsky
Principal Investigator
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
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Sasha Bernatsky, MD/PhD
Role: PRINCIPAL_INVESTIGATOR
Research Institute of the McGill University Health Centre
Locations
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Research Institute of the McGill University Health Centre
Montreal, Quebec, Canada
Site Status
RECRUITING
Countries
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Canada
Central Contacts
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References
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Keeling SO, Alabdurubalnabi Z, Avina-Zubieta A, Barr S, Bergeron L, Bernatsky S, Bourre-Tessier J, Clarke A, Baril-Dionne A, Dutz J, Ensworth S, Fifi-Mah A, Fortin PR, Gladman DD, Haaland D, Hanly JG, Hiraki LT, Hussein S, Legault K, Levy D, Lim L, Matsos M, McDonald EG, Medina-Rosas J, Pardo Pardi J, Peschken C, Pineau C, Pope J, Rader T, Reynolds J, Silverman E, Tselios K, Suitner M, Urowitz M, Touma Z, Vinet E, Santesso N. Canadian Rheumatology Association Recommendations for the Assessment and Monitoring of Systemic Lupus Erythematosus. J Rheumatol. 2018 Oct;45(10):1426-1439. doi: 10.3899/jrheum.171459. Epub 2018 Sep 1.
Reference Type
BACKGROUND
Jonsen A, Clarke AE, Joseph L, Belisle P, Bernatsky S, Nived O, Bengtsson AA, Sturfelt G, Pineau CA. Association of the Charlson comorbidity index with mortality in systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2011 Sep;63(9):1233-7. doi: 10.1002/acr.20506.
Reference Type
BACKGROUND
Akhavan PS, Su J, Lou W, Gladman DD, Urowitz MB, Fortin PR. The early protective effect of hydroxychloroquine on the risk of cumulative damage in patients with systemic lupus erythematosus. J Rheumatol. 2013 Jun;40(6):831-41. doi: 10.3899/jrheum.120572. Epub 2013 Apr 15.
Reference Type
BACKGROUND
Levy DM, Peschken CA, Tucker LB, Chedeville G, Huber AM, Pope JE; Canadian Network for Improved Outcomes in SLE (CaNIOS) 1000 Faces Investigators; Silverman ED. Association of health-related quality of life in childhood-onset systemic lupus erythematosus with ethnicity: results from a multiethnic multicenter Canadian cohort. Arthritis Care Res (Hoboken). 2014 Dec;66(12):1767-74. doi: 10.1002/acr.22363.
Reference Type
BACKGROUND
Aghdassi E, Zhang W, St-Pierre Y, Clarke AE, Morrison S, Peeva V, Landolt-Marticorena C, Su J, Reich H, Scholey J, Herzenberg A, Pope JE, Peschken C; LuNNET CaNIOS Investigators; Wither JE, Fortin PR. Healthcare cost and loss of productivity in a Canadian population of patients with and without lupus nephritis. J Rheumatol. 2011 Apr;38(4):658-66. doi: 10.3899/jrheum.100482. Epub 2010 Dec 15.
Reference Type
BACKGROUND
Peschken CA, Katz SJ, Silverman E, Pope JE, Fortin PR, Pineau C, Smith CD, Arbillaga HO, Gladman DD, Urowitz M, Zummer M, Clarke A, Bernatsky S, Hudson M; Canadian Network for Improved Outcomes in Systemic Lupus Erythematosus (CaNIOS). The 1000 Canadian faces of lupus: determinants of disease outcome in a large multiethnic cohort. J Rheumatol. 2009 Jun;36(6):1200-8. doi: 10.3899/jrheum.080912. Epub 2009 Apr 15.
Reference Type
BACKGROUND
Bruce IN, O'Keeffe AG, Farewell V, Hanly JG, Manzi S, Su L, Gladman DD, Bae SC, Sanchez-Guerrero J, Romero-Diaz J, Gordon C, Wallace DJ, Clarke AE, Bernatsky S, Ginzler EM, Isenberg DA, Rahman A, Merrill JT, Alarcon GS, Fessler BJ, Fortin PR, Petri M, Steinsson K, Dooley MA, Khamashta MA, Ramsey-Goldman R, Zoma AA, Sturfelt GK, Nived O, Aranow C, Mackay M, Ramos-Casals M, van Vollenhoven RF, Kalunian KC, Ruiz-Irastorza G, Lim S, Kamen DL, Peschken CA, Inanc M, Urowitz MB. Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort. Ann Rheum Dis. 2015 Sep;74(9):1706-13. doi: 10.1136/annrheumdis-2013-205171. Epub 2014 May 16.
Reference Type
BACKGROUND
Lee J, Dhillon N, Pope J. All-cause hospitalizations in systemic lupus erythematosus from a large Canadian referral centre. Rheumatology (Oxford). 2013 May;52(5):905-9. doi: 10.1093/rheumatology/kes391. Epub 2013 Jan 9.
Reference Type
BACKGROUND
Garcia-Gonzalez A, Richardson M, Garcia Popa-Lisseanu M, Cox V, Kallen MA, Janssen N, Ng B, Marcus DM, Reveille JD, Suarez-Almazor ME. Treatment adherence in patients with rheumatoid arthritis and systemic lupus erythematosus. Clin Rheumatol. 2008 Jul;27(7):883-9. doi: 10.1007/s10067-007-0816-6. Epub 2008 Jan 8.
Reference Type
BACKGROUND
Koneru S, Kocharla L, Higgins GC, Ware A, Passo MH, Farhey YD, Mongey AB, Graham TB, Houk JL, Brunner HI. Adherence to medications in systemic lupus erythematosus. J Clin Rheumatol. 2008 Aug;14(4):195-201. doi: 10.1097/RHU.0b013e31817a242a.
Reference Type
BACKGROUND
Mehat P, Atiquzzaman M, Esdaile JM, AviNa-Zubieta A, De Vera MA. Medication Nonadherence in Systemic Lupus Erythematosus: A Systematic Review. Arthritis Care Res (Hoboken). 2017 Nov;69(11):1706-1713. doi: 10.1002/acr.23191. Epub 2017 Sep 21.
Reference Type
BACKGROUND
Leroux G, Costedoat-Chalumeau N, Hulot JS, Amoura Z, Frances C, Aymard G, Lechat P, Piette JC. Relationship between blood hydroxychloroquine and desethylchloroquine concentrations and cigarette smoking in treated patients with connective tissue diseases. Ann Rheum Dis. 2007 Nov;66(11):1547-8. doi: 10.1136/ard.2007.072587. No abstract available.
Reference Type
BACKGROUND
Dixon WG, Abrahamowicz M, Beauchamp ME, Ray DW, Bernatsky S, Suissa S, Sylvestre MP. Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection in older patients with rheumatoid arthritis: a nested case-control analysis. Ann Rheum Dis. 2012 Jul;71(7):1128-33. doi: 10.1136/annrheumdis-2011-200702. Epub 2012 Jan 12.
Reference Type
BACKGROUND
Widdifield J, Moura CS, Wang Y, Abrahamowicz M, Paterson JM, Huang A, Beauchamp ME, Boire G, Fortin PR, Bessette L, Bombardier C, Hanly JG, Feldman D, Bernatsky S; CAnadian Network for Advanced Interdisciplinary Methods for comparative effectiveness research (CAN-AIM). The Longterm Effect of Early Intensive Treatment of Seniors with Rheumatoid Arthritis: A Comparison of 2 Population-based Cohort Studies on Time to Joint Replacement Surgery. J Rheumatol. 2016 May;43(5):861-8. doi: 10.3899/jrheum.151156. Epub 2016 Feb 15.
Reference Type
BACKGROUND
Moura CS, Abrahamowicz M, Beauchamp ME, Lacaille D, Wang Y, Boire G, Fortin PR, Bessette L, Bombardier C, Widdifield J, Hanly JG, Feldman D, Maksymowych W, Peschken C, Barnabe C, Edworthy S, Bernatsky S; CAN-AIM. Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large population-based study. Arthritis Res Ther. 2015 Aug 3;17(1):197. doi: 10.1186/s13075-015-0713-3.
Reference Type
BACKGROUND
Sylvestre MP, Abrahamowicz M. Flexible modeling of the cumulative effects of time-dependent exposures on the hazard. Stat Med. 2009 Nov 30;28(27):3437-53. doi: 10.1002/sim.3701.
Reference Type
BACKGROUND
Marmor MF, Carr RE, Easterbrook M, Farjo AA, Mieler WF; American Academy of Ophthalmology. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy: a report by the American Academy of Ophthalmology. Ophthalmology. 2002 Jul;109(7):1377-82. doi: 10.1016/s0161-6420(02)01168-5. No abstract available.
Reference Type
BACKGROUND
Sun X, Li X, Chen C, Song Y. A review of statistical issues with progression-free survival as an interval-censored time-to-event endpoint. J Biopharm Stat. 2013;23(5):986-1003. doi: 10.1080/10543406.2013.813524.
Reference Type
BACKGROUND
Wynant W, Abrahamowicz M. Flexible estimation of survival curves conditional on non-linear and time-dependent predictor effects. Stat Med. 2016 Feb 20;35(4):553-65. doi: 10.1002/sim.6740. Epub 2015 Nov 6.
Reference Type
BACKGROUND
Wynant W, Abrahamowicz M. Impact of the model-building strategy on inference about nonlinear and time-dependent covariate effects in survival analysis. Stat Med. 2014 Aug 30;33(19):3318-37. doi: 10.1002/sim.6178. Epub 2014 Apr 22.
Reference Type
BACKGROUND
Reed Johnson F, Lancsar E, Marshall D, Kilambi V, Muhlbacher A, Regier DA, Bresnahan BW, Kanninen B, Bridges JF. Constructing experimental designs for discrete-choice experiments: report of the ISPOR Conjoint Analysis Experimental Design Good Research Practices Task Force. Value Health. 2013 Jan-Feb;16(1):3-13. doi: 10.1016/j.jval.2012.08.2223.
Reference Type
BACKGROUND
Black N, Burke L, Forrest CB, Sieberer UH, Ahmed S, Valderas JM, Bartlett SJ, Alonso J. Patient-reported outcomes: pathways to better health, better services, and better societies. Qual Life Res. 2016 May;25(5):1103-12. doi: 10.1007/s11136-015-1168-3. Epub 2015 Nov 13.
Reference Type
BACKGROUND
Neville C, DaCosta D, Rochon M, Eng D, Fortin PR. Toward the development of a lupus interactive navigator to facilitate patients and their health care providers in the management of lupus: results of web-based surveys. JMIR Res Protoc. 2014 Dec 22;3(4):e65. doi: 10.2196/resprot.3349.
Reference Type
BACKGROUND
Bernatsky S, Peschken C, Fortin PR, Pineau CA, Urowitz MB, Gladman DD, Pope JE, Hudson M, Zummer M, Smith CD, Arbillaga HO, Clarke AE; Canadian Network for Improved Outcomes in Systemic Lupus Erythematosus (CaNIOS). Medication use in systemic lupus erythematosus. J Rheumatol. 2011 Feb;38(2):271-4. doi: 10.3899/jrheum.100414. Epub 2010 Nov 15.
Reference Type
BACKGROUND
Clarke AE, Urowitz MB, Monga N, Hanly JG. Costs associated with severe and nonsevere systemic lupus erythematosus in Canada. Arthritis Care Res (Hoboken). 2015 Mar;67(3):431-6. doi: 10.1002/acr.22452.
Reference Type
BACKGROUND
Mahler M, Parker T, Peebles CL, Andrade LE, Swart A, Carbone Y, Ferguson DJ, Villalta D, Bizzaro N, Hanly JG, Fritzler MJ. Anti-DFS70/LEDGF antibodies are more prevalent in healthy individuals compared to patients with systemic autoimmune rheumatic diseases. J Rheumatol. 2012 Nov;39(11):2104-10. doi: 10.3899/jrheum.120598. Epub 2012 Sep 1.
Reference Type
BACKGROUND
Furst DE, Clarke A, Fernandes AW, Bancroft T, Gajria K, Greth W, Iorga SR. Resource utilization and direct medical costs in adult systemic lupus erythematosus patients from a commercially insured population. Lupus. 2013 Mar;22(3):268-78. doi: 10.1177/0961203312474087. Epub 2013 Jan 22.
Reference Type
BACKGROUND
Isenberg DA, Gladman D. The Systemic Lupus International Collaborating Clinics Group--origins and outcomes. Lupus. 2001;10(5):375-7. doi: 10.1191/096120301676101377. No abstract available.
Reference Type
BACKGROUND
Isenberg DA, Ramsey-Goldman R, Gladman D, Hanly JG. The Systemic Lupus International Collaborating Clinics (SLICC) group - it was 20 years ago today. Lupus. 2011 Nov;20(13):1426-32. doi: 10.1177/0961203311421501.
Reference Type
BACKGROUND
Lee J, Peschken CA, Muangchan C, Silverman E, Pineau C, Smith CD, Arbillaga H, Zummer M, Clarke A, Bernatsky S, Hudson M, Hitchon C, Fortin PR, Pope JE. The frequency of and associations with hospitalization secondary to lupus flares from the 1000 Faces of Lupus Canadian cohort. Lupus. 2013 Nov;22(13):1341-8. doi: 10.1177/0961203313505689. Epub 2013 Sep 18.
Reference Type
BACKGROUND
Bernatsky S, Ramsey-Goldman R, Labrecque J, Joseph L, Boivin JF, Petri M, Zoma A, Manzi S, Urowitz MB, Gladman D, Fortin PR, Ginzler E, Yelin E, Bae SC, Wallace DJ, Edworthy S, Jacobsen S, Gordon C, Dooley MA, Peschken CA, Hanly JG, Alarcon GS, Nived O, Ruiz-Irastorza G, Isenberg D, Rahman A, Witte T, Aranow C, Kamen DL, Steinsson K, Askanase A, Barr S, Criswell LA, Sturfelt G, Patel NM, Senecal JL, Zummer M, Pope JE, Ensworth S, El-Gabalawy H, McCarthy T, Dreyer L, Sibley J, St Pierre Y, Clarke AE. Cancer risk in systemic lupus: an updated international multi-centre cohort study. J Autoimmun. 2013 May;42:130-5. doi: 10.1016/j.jaut.2012.12.009. Epub 2013 Feb 12.
Reference Type
BACKGROUND
Bernatsky S, Ramsey-Goldman R, Joseph L, Boivin JF, Costenbader KH, Urowitz MB, Gladman DD, Fortin PR, Nived O, Petri MA, Jacobsen S, Manzi S, Ginzler EM, Isenberg D, Rahman A, Gordon C, Ruiz-Irastorza G, Yelin E, Bae SC, Wallace DJ, Peschken CA, Dooley MA, Edworthy SM, Aranow C, Kamen DL, Romero-Diaz J, Askanase A, Witte T, Barr SG, Criswell LA, Sturfelt GK, Blanco I, Feldman CH, Dreyer L, Patel NM, St Pierre Y, Clarke AE. Lymphoma risk in systemic lupus: effects of disease activity versus treatment. Ann Rheum Dis. 2014 Jan;73(1):138-42. doi: 10.1136/annrheumdis-2012-202099. Epub 2013 Jan 8.
Reference Type
BACKGROUND
Bernatsky S, Clarke A, Gladman DD, Urowitz M, Fortin PR, Barr SG, Senecal JL, Zummer M, Edworthy S, Sibley J, Pope J, Ensworth S, Ramsey-Goldman R, Hanly JG. Mortality related to cerebrovascular disease in systemic lupus erythematosus. Lupus. 2006;15(12):835-9. doi: 10.1177/0961203306073133.
Reference Type
BACKGROUND
Bernatsky S, Boivin JF, Joseph L, Manzi S, Ginzler E, Gladman DD, Urowitz M, Fortin PR, Petri M, Barr S, Gordon C, Bae SC, Isenberg D, Zoma A, Aranow C, Dooley MA, Nived O, Sturfelt G, Steinsson K, Alarcon G, Senecal JL, Zummer M, Hanly J, Ensworth S, Pope J, Edworthy S, Rahman A, Sibley J, El-Gabalawy H, McCarthy T, St Pierre Y, Clarke A, Ramsey-Goldman R. Mortality in systemic lupus erythematosus. Arthritis Rheum. 2006 Aug;54(8):2550-7. doi: 10.1002/art.21955.
Reference Type
BACKGROUND
Lu M, Bernatsky S, Ramsey-Goldman R, Petri M, Manzi S, Urowitz MB, Gladman D, Fortin PR, Ginzler EM, Yelin E, Bae SC, Wallace DJ, Jacobsen S, Dooley MA, Peschken CA, Alarcon GS, Nived O, Gottesman L, Criswell LA, Sturfelt G, Dreyer L, Lee JL, Clarke AE. Non-lymphoma hematological malignancies in systemic lupus erythematosus. Oncology. 2013;85(4):235-40. doi: 10.1159/000350165. Epub 2013 Oct 2.
Reference Type
BACKGROUND
Steiner JF, Koepsell TD, Fihn SD, Inui TS. A general method of compliance assessment using centralized pharmacy records. Description and validation. Med Care. 1988 Aug;26(8):814-23. doi: 10.1097/00005650-198808000-00007.
Reference Type
BACKGROUND
Bernatsky S, Joseph L, Pineau CA, Tamblyn R, Feldman DE, Clarke AE. A population-based assessment of systemic lupus erythematosus incidence and prevalence--results and implications of using administrative data for epidemiological studies. Rheumatology (Oxford). 2007 Dec;46(12):1814-8. doi: 10.1093/rheumatology/kem233.
Reference Type
RESULT
Canadian Hydroxychloroquine Study Group. A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. N Engl J Med. 1991 Jan 17;324(3):150-4. doi: 10.1056/NEJM199101173240303.
Reference Type
RESULT
Tsakonas E, Joseph L, Esdaile JM, Choquette D, Senecal JL, Cividino A, Danoff D, Osterland CK, Yeadon C, Smith CD. A long-term study of hydroxychloroquine withdrawal on exacerbations in systemic lupus erythematosus. The Canadian Hydroxychloroquine Study Group. Lupus. 1998;7(2):80-5. doi: 10.1191/096120398678919778.
Reference Type
RESULT
Waldron N, Brown S, Hewlett S, Elliott B, McHugh N, McCabe C. 'It's more scary not to know': a qualitative study exploring the information needs of patients with systemic lupus erythematosus at the time of diagnosis. Musculoskeletal Care. 2011 Dec;9(4):228-38. doi: 10.1002/msc.221. Epub 2011 Oct 13.
Reference Type
RESULT
Telek HH, Yesilirmak N, Sungur G, Ozdemir Y, Yesil NK, Ornek F. Retinal toxicity related to hydroxychloroquine in patients with systemic lupus erythematosus and rheumatoid arthritis. Doc Ophthalmol. 2017 Dec;135(3):187-194. doi: 10.1007/s10633-017-9607-9. Epub 2017 Aug 29.
Reference Type
RESULT
Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M, Bacon P, Bombardieri S, Hanly J, Hay E, Isenberg D, Jones J, Kalunian K, Maddison P, Nived O, Petri M, Richter M, Sanchez-Guerrero J, Snaith M, Sturfelt G, Symmons D, Zoma A. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum. 1996 Mar;39(3):363-9. doi: 10.1002/art.1780390303.
Reference Type
RESULT
Yee CS, Farewell VT, Isenberg DA, Griffiths B, Teh LS, Bruce IN, Ahmad Y, Rahman A, Prabu A, Akil M, McHugh N, Edwards C, D'Cruz D, Khamashta MA, Gordon C. The use of Systemic Lupus Erythematosus Disease Activity Index-2000 to define active disease and minimal clinically meaningful change based on data from a large cohort of systemic lupus erythematosus patients. Rheumatology (Oxford). 2011 May;50(5):982-8. doi: 10.1093/rheumatology/keq376. Epub 2011 Jan 18.
Reference Type
RESULT
Ward MM, Marx AS, Barry NN. Comparison of the validity and sensitivity to change of 5 activity indices in systemic lupus erythematosus. J Rheumatol. 2000 Mar;27(3):664-70.
Reference Type
RESULT
Satagopan JM, Ben-Porat L, Berwick M, Robson M, Kutler D, Auerbach AD. A note on competing risks in survival data analysis. Br J Cancer. 2004 Oct 4;91(7):1229-35. doi: 10.1038/sj.bjc.6602102.
Reference Type
RESULT
Hazlewood GS, Bombardier C, Tomlinson G, Thorne C, Bykerk VP, Thompson A, Tin D, Marshall DA. Treatment preferences of patients with early rheumatoid arthritis: a discrete-choice experiment. Rheumatology (Oxford). 2016 Nov;55(11):1959-1968. doi: 10.1093/rheumatology/kew280. Epub 2016 Jul 31.
Reference Type
RESULT
Petri M, Genovese M, Engle E, Hochberg M. Definition, incidence, and clinical description of flare in systemic lupus erythematosus. A prospective cohort study. Arthritis Rheum. 1991 Aug;34(8):937-44. doi: 10.1002/art.1780340802.
Reference Type
RESULT
Hoaglin DC, Hawkins N, Jansen JP, Scott DA, Itzler R, Cappelleri JC, Boersma C, Thompson D, Larholt KM, Diaz M, Barrett A. Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2. Value Health. 2011 Jun;14(4):429-37. doi: 10.1016/j.jval.2011.01.011.
Reference Type
RESULT
Haase KR, Loiselle CG. Oncology team members' perceptions of a virtual navigation tool for cancer patients. Int J Med Inform. 2012 Jun;81(6):395-403. doi: 10.1016/j.ijmedinf.2011.11.001. Epub 2012 Jan 13.
Reference Type
RESULT
Loiselle CG, Peters O, Haase KR, Girouard L, Korner A, Wiljer D, Fitch M. Virtual navigation in colorectal cancer and melanoma: an exploration of patients' views. Support Care Cancer. 2013 Aug;21(8):2289-96. doi: 10.1007/s00520-013-1771-1. Epub 2013 Mar 22.
Reference Type
RESULT
Neville C, Da Costa D, Rochon M, Peschken CA, Pineau CA, Bernatsky S, Keeling S, Avina-Zubieta A, Lye E, Eng D, Fortin PR. Development of the Lupus Interactive Navigator as an Empowering Web-Based eHealth Tool to Facilitate Lupus Management: Users Perspectives on Usability and Acceptability. JMIR Res Protoc. 2016 May 30;5(2):e44. doi: 10.2196/resprot.4219.
Reference Type
RESULT
Moss KE, Ioannou Y, Sultan SM, Haq I, Isenberg DA. Outcome of a cohort of 300 patients with systemic lupus erythematosus attending a dedicated clinic for over two decades. Ann Rheum Dis. 2002 May;61(5):409-13. doi: 10.1136/ard.61.5.409.
Reference Type
RESULT
Clowse ME, Magder L, Witter F, Petri M. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum. 2006 Nov;54(11):3640-7. doi: 10.1002/art.22159.
Reference Type
RESULT
Related Links
Access external resources that provide additional context or updates about the study.
https://www.aao.org/clinical-statement/revised-recommendations-on-screening-chloroquine-h
AAO Quality of Care Secretariat, Hoskins Center for Quality Eye Care Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy Ophthalmology
http://canaim.ca/about-us
CAnadian Network for Advanced Interdisciplinary Methods for comparative effectiveness research
http://www.jrheum.org/content/42/12/2318.full.pdf
Lack of Interferon and Proinflammatory Cyto/chemokines in Serologically Active Clinically Quiescent SLE.
https://grants.nih.gov/grants/guide/rfa-files/RFA-OD-19-012.html
Racial and Ethnic Categories and Definitions
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012002/
Purposeful sampling for qualitative data collection and analysis in mixed method implementation research. Administration and policy in mental health
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
MP-37-2019-4340
Identifier Type: -
Identifier Source: org_study_id
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