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Arthritis Research Canada at

ACR Convergence 2022

November 13

The Impact of Early Antimalarial Adherence on Future Acute Care Utilization Among Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients: A Population-based Study

This study of people with lupus and rheumatoid arthritis across British Columbia found that when people take antimalarial drugs, like hydroxychloroquine, as prescribed, this lowers their risk of needing to use health care services in the future (12% lower risk of hospital admission and 22% reduction in the number of days spent in hospital) compared to when patients don’t take their medications as prescribed.

Research Team: Hoque R, Avina-Zubieta JA, Lacaille D, De Vera M, Qian Y, Esdaile J, Xie H.

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Accessing Telehealth and In-Person Healthcare during the COVID-19 Pandemic: Experiences of Individuals with Rheumatoid Arthritis.

This qualitative study provides valuable insights into how individuals with rheumatoid arthritis experienced seeking health services in British Columbia during the COVID-19 pandemic. Findings can inform the use of telehealth post-pandemic through addressing patient concerns, personalizing telehealth options, and integrating telehealth into clinical practice for routine check-ups.

Research Team: Ramachandran SO, Leese J, Therrien S, Backman CL, Ma J, English K, Davidson E, McQuitty S, Hoens AM, Koehn C, Gavin J, Adams J, Li LC.

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Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE)-like Syndrome After Immune Checkpoint Inhibition: A CanRIO Study

Medications used to treat cancer by turning on the immune system so it can better fight the cancer also have an increased risk of auto-immune diseases as complications of treatment. One example, is a type of arthritis with inflammation of the small joints of the hands and edema of the limb, called RS3PE. It can occur even after the cancer treatment is stopped and flare after it is restarted. Optimal treatment remains to be determined.

Research Team: Rouhi A, Jamal S, Hudson M, Pope J, Roberts J, Ladouceur A, Hewitt S, Ye C.

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Effect of Tailored Self-Management Interventions on Health Outcomes in Individuals with Chronic Musculoskeletal Conditions

Self-care is an important practice for managing arthritis. There are many programs that supports people to manage the day-to-day arthritis symptoms; most of them work, but the effects are modest. Tailoring is the act of matching care to an individual’s needs, goals, health status and behaviours. This systematic review examined the effectiveness of tailored self-care interventions across health and behavioural outcomes. Findings suggest that tailoring may have additional benefits for pain and self-efficacy, however study designs were diverse, and reporting was inconsistent.

Research Team: Wang E, Rodrigues IB, Li LC.

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ANA-positive versus ANA-negative Antiphospholipid Antibody-positive Patients Without Other Systemic Autoimmune Diseases: Clinical and Serological Characteristics, Results from the APS ACTION Clinical Database and Repository

In this large international study following people with antiphospholipid syndrome, a condition that increases the risk of blood clots, having another positive antibody called ANA was associated with a higher rate of abnormalities of blood cells. People with a positive ANAhad a tendency toward a higher rate of arthritis and abnormalities of the small blood vessels.  People with a negative ANA had higher rates of clots in the arteries.

Research Team: Cecchi I, Radin M, Grazietta Foddai S, Bertolaccini ML, De Andrade D, Tektonidou M, Pengo V, Ruiz-Irastorza G, Belmont HM, Gerosa M, Fortin P, Lopez-Pedrera C, Zhang Z, Atsumi T, de Jesus G, Cohen H, Kello N, Branch W, Wahl D, Andreoli L, Rodriguez E, Petri M, Barber MRW, Cervera R, Knight J, Artim-Esen B, Willis R, Pons-Estel G, Erkan D, Sciascia S.

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Thrombocytopenia and Autoimmune Hemolytic Anemia in Antiphospholipid Antibody-positive Patients: Descriptive Analysis of the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository (“Registry”).

 

In this large international study of people with a positive antibody (antiphospholipid antibody) which increases the risk of blood clots, one-fifth of people also had a history of low platelets or anemia due to antibodies against blood cells. Half of these patients also had additional features of lupus. They were also more likely to have abnormalities of the small blood vessels and/or of the heart valves, suggesting a more severe clinical phenotype.

Research Team: Erton ZB, Leaf RK, Oliveira de Andrade DC, Barber M, Tektonidou MG, Pengo V, Sciascia S, AUgarte A, Belmont HM, López-Pedrera C, Fortin PR, Gerosa M, de Jesús G, Tatsumi T, Zhang Z, Cohen H, Branch WD, Wahl, Andreoli DL, Rodriguez Almaraz E, Petri MM, Cervera R, Zuo Y, Artim-Esen B, Willis R, Bertolaccini ML, Roubey R, Erkan D, and on behalf of APS ACTION.

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Single Antiphospholipid Antibody Positive Thrombotic APS Patients’ Clinical Characteristics: Retrospective Results from the APS ACTION Clinical Database and Repository (Registry)

This international study of people with positive antiphospholipid syndrome without other systemic autoimmune diseases found that approximately one third of patients have only one antibody positive that increases the risk of clotting, and it is most commonly the “lupus anticoagulant” antibody (and approximately one-third of these patients have history of recurrent blood clots).

Research Team:Grazietta Foddai S, Cecchi I, Radin M, De Andrade D, Tektonidou M, Pengo V, Ruiz-Irastorza G, Belmont HM, Gerosa M, Fortin P, Lopez-Pedrera R, Zhang Z, Atsumi T, de Jesus G, Cohen H, Kello N, Branch W, Wahl D, Andreoli L, Rodriguez E, Petri M, Clarke AE, Cervera R, Knight J, Artim-Esen B, Willis R, Pons-Estel G, Erkan D, Roccatello D, Sciascia S.

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Identification of Outcome Domains in Immune Checkpoint Inhibitor-Induced Inflammatory Arthritis and Polymyalgia Rheumatica: A Scoping Review by the OMERACT IrAE Working Group

This international group of researchers dedicated to harmonizing how outcomes are measured for research did a review of the literature to identify the important groups of clinical features that need to be captured when trying to define inflammatory arthritis and polymyalgia rheumatica occurring as a side-effect of cancer drugs called immune checkpoint inhibitors. In addition to specific manifestations that describe the pathophysiology of the disease, other areas deemed important to measure included the impact of these conditions on daily life, survival and resource use.

Research Team:Ghosh N, Couette N, van Binsbergen W, Weinmann S, Jivanelli B, Shea B, Bass A, Benesova K, Bingham III CO, Calabrese C, Cappelli LC, Chan K, Choy E, Daoussis D, Goodman S, Hudson M, Jamal S, Leipe J, Lopez-Olivo MA, Suarez-Almazor M, van der Laken C, Meara A, Liew D, Kostine M

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Prevalence of Autoimmune Conditions in Metastatic Melanoma Patients Starting Checkpoint Inhibitors

Pre-existing autoimmune conditions are present in a considerable number of patients with metastatic melanoma who are treated with a class of cancer medications called immune checkpoint inhibitors. These medications drastically improve outcomes in metastatic melanoma, but adverse events in people with pre-existing autoimmune conditions are a concern and need to be evaluated in future studies.

Research Team: Ladouceur A, De Avila Machado MA, Hudson M, Moura C, Bernatsky S.

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Clinically Recognized Depression and Mental Health Treatment in a Single Center Cohort of Patients with Systemic Sclerosis

We studied a group of systemic sclerosis patients over several years. We found more than a quarter of the patients had significant depressive symptoms. Yet, only a minority (20%) of participants with probable depression were not clinically diagnosed or treated for a mental health condition. People with scleroderma who had involvement of their lungs (Shortness of breath), or of their stomach and bowel, were more likely to also experience depression.

Research Team: Savoie M, Poeschla A, Lu N, Zhang Y, Bolster M, Schoenfeld S, Castelino F.

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Accurate Identification of ANCA-Associated Vasculitis Cases from Clinical Notes Using Machine Learning

ML models, especially XGBoost and deep learning, can accurately classify clinical note sections as reflecting a diagnosis of AAV. Models trained using a data set with keyword filtering were generalizable to a data set without applying keyword filtering. Future studies might apply the models to screen the entire MGB database for AAV cases using clinical notes and compare these approaches to rule-based algorithms.

Research Team: Wang L, Laurentiev J, Cook C, Miloslavsky E, Choi H, Zhou L, Wallace Z.

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The Epidemiology, Clinical Outcomes, and Healthcare Resource Utilization of IgG4-Related Disease Among Commercially Insured People in the United States

In this first large-scale outcomes study of IgG4-RD in the US, we have found both the clinical and HCRU burdens are substantial. The prevalence of IgG4-RD is likely underestimated given the recent recognition of the disease entity. Nevertheless, IgG4-RD is at least as common as ANCA vasculitis and systemic sclerosis. Hepatobiliary disease was the most common manifestation and glucocorticoids the most frequent treatment, which are reflected in the excess comorbidity burden of IgG4-RD patients, including pancreatic insufficiency and glucocorticoid toxicities. These findings support the need for effective steroid-sparing therapies for IgG4-RD and studies evaluating malignancy in IgG4-RD.

Research Team: Wallace Z, Miles G, Smolkina E, Petruski-Ivleva N, Madziva D, Cook C, Fu X, Zhang Y, Stone J, Choi H.

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Identification of Novel Proteomic Biomarkers of Disease Activity in ANCA-Associated Vasculitis Using a High Throughput Approach

Using a high-throughput approach, we identified novel candidate markers differentiating active disease from remission and positive vs negative ANCA. These proteins reflect diverse aspects of the immune response. The potential for biomarkers that distinguish ANCA positive from negative status, especially among people in remission, suggests that patients in clinical remission with persistently positive ANCA may have ongoing inflammation that could contribute to subclinical damage. Indeed, a prior study found that IL-12 production by dendritic cells was decreased in patients with active vs remission AAV. These findings require validation in additional cohorts, using longitudinal serial samples, and confirmatory methods.

Research Team: Wallace Z, Joshi A, Fu X, Cook C, Zhang Y, Choi H.

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IgG Antibody Subclass Glycan Modifications in Patients with ANCA-Associated Vasculitis in Active vs Remission States – a Proof-of-Concept Study

This proof-of-concept study suggests strong trends in glycosylation pattern differences of IgG1, IgG2, and IgG4 when comparing MPO-ANCA+ AAV patients with active disease vs those in remission, despite having persistently elevated ANCA titers. In particular, active MPO-ANCA+ AAV was characterized by a greater proportion of agalactosylated antibody, similar to what has been described in PR3-ANCA+ AAV. These results, in combination with prior studies, suggest that differences in glycosylation may be a promising avenue for future investigation in both PR3- and MPO-ANCA+ AAV where reliable biomarkers of disease activity are urgently needed. These data call for a full-scale investigation to assess MPO- and PR3-ANCA and leverage longitudinal serial samples to further assess glycosylation patterns as a biomarker.

Research Team: Wallace Z, Motazedi T, Conroy M, Cook C, Stone J, Choi H, Anthony R.

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Adherence to Early DMARD Strategies in Newly Diagnosed RA Patients Seen in Routine Care: Results from the Canadian Early Arthritis Cohort Study

This Canadian study of people with early rheumatoid arthritis followed in real-world routine care found that approximately 1/6 of RA patients reported low or moderate adherence to the RA treatment they were prescribed, in the first 6 months of their disease. Non-adherence was mainly non-intentional (e.g. forgetting to take medications). Intentionally not taking one’s meds was associated with a lower likelihood of good treatment outcome, such as reaching treatment targets.

Research Team: Jiang Y, Schieir O, Valois MF, Bartlett S, Bessette L, Boire G, Hazlewood G, Hitchon C, Keystone E, Tin D, Thorne C, Bykerk V, Pope J, and Canadian Early Arthritis Cohort (CATCH) Investigators.

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Work Disability and Function in Systematic Lupus Erythematosus (SLE): Results from a Mixed-Methods Exploratory Canadian Study

A study across Canada of people living with systemic lupus erythematosus (SLE) found that they experience important limitations in their ability to do their work. This was found to be partly due to intrinsic factors (e.g., disease flares) and extrinsic factors (e.g., work environment)

Research Team: Nowrouzi-Kia B, Avina-Zubieta JA, Fox MT, Shaw W, Ho M, Haaland D, Pope J, Fortin PR, Bingham K, Rozenbojm N, Matsos M, Peschken C, Steiman A, Silverman E, Su J, Reynolds J, Ivory C, Gladman D, Urowitz M, Sanchez-Guerrero F, Lim L, Keeling S, Soberanis A, Katz P, Touma Z.

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2022 Revision of the ACR/EULAR Remission Criteria for Rheumatoid Arthritis

How to best measure clinical remission in rheumatoid arthritis, i.e. when the disease becomes inactive as a result of treatment, has been highly debated. This study validated a revised version of a prior remission criteria, which allows a mild degree of pain as long as no swelling is present, to account for mild pain due to joint damage or other causes besides inflammation. This addresses prior concerns with this criteria. The study showed the revised criteria performed very well and predicted future lack of joint damage on X-Ray and good functional outcomes.

Research Team: Studenic P, Aletaha D, de Wit M, Stamm T, Alasti F, Lacaille D, Smolen J, Felson D.

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Comparative Effectiveness of BNT162b2 and mRNA-1273 Vaccines Against COVID-19 Infection Among Patients with Systemic Autoimmune Rheumatic Diseases

Among SARDs on immunomodulators, the risk of breakthrough COVID-19 infection is low after receiving either BNT162b2 or mRNA-1273. However, there was a trend toward greater benefit with mRNA-1273 vs BNT162b2, especially prior to a 3rd vaccine dose and the Omicron wave. These results are similar to previous observations made in the general population1. Ongoing real-world studies are needed to investigate the risk of breakthrough infection among SARDs as vaccination and mitigation strategies, infection rates, and new variants evolve.

Research Team: Cook C, Patel N, Fu X, Wang X, Kawano Y, Vanni K, Qian G, Banasiak E, Kowalski E, Choi H, Zhang Y, Sparks J, Wallace Z.

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