To determine the comparative effectiveness of oral versus subcutaneous methotrexate (MTX) as initial therapy for patients with early rheumatoid arthritis (ERA). Patients with ERA (symptoms ≤1 year) initiating MTX therapy were included... more
To determine the comparative effectiveness of oral versus subcutaneous methotrexate (MTX) as initial therapy for patients with early rheumatoid arthritis (ERA). Patients with ERA (symptoms ≤1 year) initiating MTX therapy were included from a multicentre, prospective cohort study. We compared the effectiveness between starting with oral versus subcutaneous MTX over the first year. Longitudinal multivariable models, adjusted for potential baseline and time-varying confounders, were used to compare treatment changes due to inefficacy or toxicity and treatment efficacy (Disease Activity Score-28 (DAS-28), DAS-28 remission and Health Assessment Questionnaire-Disability Index (HAQ-DI)). 666 patients were included (417 oral MTX, 249 subcutaneous MTX). Patients prescribed subcutaneous MTX were prescribed a higher dose of MTX (mean dose over first three months 22.3 mg vs 17.2 mg/week). At 1 year, 49% of patients initially treated with subcutaneous MTX had changed treatment compared with 77% treated with oral MTX. After adjusting for potential confounders, subcutaneous MTX was associated with a lower rate of treatment failure ((HR (95% CI) 0.55 (0.39 to 0.79)). Most treatment failures were due to inefficacy with no difference in failure due to toxicity. In multivariable models, subcutaneous MTX was also associated with lower average DAS-28 scores (mean difference (-0.38 (95% CI -0.64 to -0.10)) and a small difference in DAS-28 remission (OR 1.2 (95% CI 1.1 to 1.3)). There was no significant difference in sustained remission or HAQ-DI (p values 0.43 and 0.75). Initial treatment with subcutaneous MTX was associated with lower rates of treatment changes, no difference in toxicity and some improvements in disease control versus oral MTX over the first year in patients with ERA.
Research Interests: Immunology, Rheumatoid Arthritis, Medicine, Multivariate Analysis, Prospective studies, and 14 moreHumans, Internal Medicine, Female, Male, Clinical Sciences, Middle Aged, Longitudinal Studies, Adult, Public health systems and services research, Time Factors, Methotrexate, Comparative Effectiveness Research, Severity of Illness Index, and Treatment Failure
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Background Methotrexate is the cornerstone DMARD in the treatment of rheumatoid arthritis. The exact mechanism of action is elusive, but it may be related to increase in adenosine levels. Methotrexate may be increasing the adenosine... more
Background Methotrexate is the cornerstone DMARD in the treatment of rheumatoid arthritis. The exact mechanism of action is elusive, but it may be related to increase in adenosine levels. Methotrexate may be increasing the adenosine levels by blocking its natural conversion to uric acid. Objectives The purpose of this study was to determine if methotrexate therapy lowers serum uric acid levels in patients with early rheumatoid arthritis compared to controls who were not treated with methotrexate. Methods Data were obtained from CATCH (Canadian Early Arthritis Cohort), a prospective early RA cohort. This was a nested case control study. All patients with methotrexate use and a diagnosis of early rheumatoid arthritis (ERA) were included if they had a serum uric acid performed before starting methotrexate and again while taking methotrexate. Patients with ERA who did not receive any methotrexate were used as controls if they had serial uric acid measurements. Results Forty-nine ERA patients, out of 2524, in the CATCH database on methotrexate therapy with serial serum uric acid measurements were identified. In this group, the mean pre-methotrexate uric acid level was 300 μmol/L with a mean post-methotrexate uric acid level of 273 μmol/L (p 0.035). The control group of ERA patients not taking methotrexate during this time had a mean baseline uric acid level of 280 μmol/L and a follow-up level of 282 μmol/L (p 0.448). The mean change in uric acid levels in serum in patients treated with methotrexate was -26.8 μmol/L, while the control group had a mean change of 2.3 μmol/L (p=0.042). Patients who experienced a decrease in serum uric acid levels in relation to their methotrexate treatment had a DAS28 score of 2.37 at 18 months, while the control group had a DAS28 of 3.26 (p=0.042). Patients treated with methotrexate who experienced a decrease in uric acid levels had a SJC28 of 0.89 at 18 months, while patients on methotrexate who did not experience a decrease in uric acid levels had a SJC28 of 4.47 (p=0.035). Conclusions Methotrexate is fundamental in the treatment of ERA and it is thought to work through increase in adenosine levels. By this postulated mechanism of action, uric acid levels were shown to be decreased in a clinical setting for patients taking methotrexate for ERA. This could be an indirect mechanism whereby methotrexate improves cardiovascular risk Disclosure of Interest None declared
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Background Tofacitinib is an oral JAK inhibitor for treatment of rheumatoid arthritis (RA). Open-label, long-term extension (LTE) studies have enrolled tofacitinib-treated patients (pts) to evaluate safety and efficacy over time. Time on... more
Background Tofacitinib is an oral JAK inhibitor for treatment of rheumatoid arthritis (RA). Open-label, long-term extension (LTE) studies have enrolled tofacitinib-treated patients (pts) to evaluate safety and efficacy over time. Time on treatment is considered a composite measure of efficacy and safety; discontinuation (D/C) is often due to lack of efficacy (LOE) and/or adverse events (AEs) for disease-modifying antirheumatic drugs (DMARDs).1 Objectives To estimate drug survival of tofacitinib up to 84 months (mo) in LTE studies and describe reasons for D/C. Methods Data were pooled from two LTE studies (NCT00413699 [up to April 2014; study ongoing, database unlocked] and NCT00661661 [completed]). Of 6553 pts from Phase (P) 1, 2 and 3 studies, 4858 pts (74.1%) received treatment in LTE studies. Tofacitinib 5 or 10 mg BID were initiated as monotherapy or with background DMARDs; pooled data and data for each dose ± background DMARDs were analysed. Pts were assigned tofacitinib 5 or 10 mg BID based on average daily dose in LTE. Kaplan-Meier (K-M) analyses estimated drug survival in tofacitinib-treated pts who withdrew for any reason, due to LOE or due to AE in the LTE, including pts who had previously responded to and tolerated treatment in P1P2P3 studies. Ongoing pts were censored as of April 2014, while pts completing the trial(s) were censored at their completion date. Safety data were included over 84 mo and efficacy data up to 72 mo due to limited pt numbers after 72 mo for efficacy. Retention data were divided into dose and mono vs combination therapy. Results 4858 pts were treated for a mean (maximum) duration of 2.5 (6.9) years (yrs) (results previously reported).2 Overall, median survival for all tofacitinib treated pts was 5.2 yrs [95% CI 5.0, 5.6] (Figure 1). Median survival for pts receiving tofacitinib with background DMARDs or as monotherapy was 5.3 [4.9, 5.7] and 5.4 [4.8, not evaluable] yrs, respectively. K-M estimates appear similar between 5 and 10 mg BID, median survival was 5.4 [4.9, 5.9] and 5.0 [4.7, 5.5] yrs, respectively (Figure 1). The D/C rate due to LOE was considerably lower than due to AEs (AEs: 17.8%, 22.9%, 15.6%; LOE: 2.7%, 3.3%, 2.5% for all tofacitinib, 5 or 10 mg BID, respectively). The most commonly reported reasons for D/C due to AEs by class were infections/infestations (7.2%, 7.8%, 7.0%), investigations (3.1%, 4.6%, 2.5%) and neoplasms (benign, malignant, unspecified) (2.7%, 3.9%, 2.1%) for all tofacitinib, 5 or 10 mg BID, respectively. Conclusions Drug survival in LTE studies provides early information on the long-term safety, efficacy and tolerability of a therapy. In this analysis, median survival of tofacitinib was approximately 5 yrs, with D/C more commonly associated with AEs than LOE. Similar survival medians were observed for the 5 and 10 mg BID dose groups and monotherapy vs background DMARD therapy. These data support the use of tofacitinib for long-term management of RA. References Neovius M et al. Ann Rheum Dis 2015; 74: 354–360. Wollenhaupt J et al. Arthritis Rheumatol 2014; 66: S375. Acknowledgement This study was sponsored by Pfizer Inc. Editorial support was provided by CMC (funded by Pfizer Inc). Disclosure of Interest J. Pope Grant/research support from: Pfizer, Consultant for: Pfizer, E. Keystone Grant/research support from: Pfizer, Consultant for: Pfizer, Speakers bureau: Pfizer, S. Jamal Grant/research support from: Pfizer, Consultant for: Pfizer, L. Wang Shareholder of: Pfizer, Employee of: Pfizer, L. Fallon Shareholder of: Pfizer, Employee of: Pfizer, J. Woolcott Shareholder of: Pfizer, Employee of: Pfizer, I. Lazariciu Consultant for: Pfizer, Employee of: Quintiles Inc, B. Haraoui Grant/research support from: Pfizer, Consultant for: Pfizer
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Background Little is known about how lifestyle factors contribute to treatment response in early RA. We examined the relationship between body mass index (BMI) and smoking on the likelihood of achieving sustained remission in patients... more
Background Little is known about how lifestyle factors contribute to treatment response in early RA. We examined the relationship between body mass index (BMI) and smoking on the likelihood of achieving sustained remission in patients with early rheumatoid arthritis (ERA). Methods ERA patients enrolled in the Canadian Early Arthritis Cohort (CATCH) with available BMI data were categorized using World Health Organization (WHO) weight categories: underweight (BMI<18.5), normal weight (BMI 18.5–24.9), overweight (BMI 25.0–29.9), obese I (BMI 30.0–34.9), II (BMI 35.0–39.9) and III (BMI>40 kg/m2). WHO-defined rates of obesity were compared to rates using RA sex-specific BMI thresholds1. Disease activity (DAS28), patient reported outcomes and medications were assessed at each visit. Multivariate regression using generalized estimating equations was used to assess the impact of BMI and smoking on achieving sustained remission (DAS28<2.6 at 2 consecutive visits). Results BMI was available in 944 patients followed up to 3 years. Patients had a mean (SD) age of 52.75 (15.07), were mostly female (72%), Caucasian (79%), and had an average disease duration of 6.30 (3.56) months. 24% of patients were classified as obese and 28% overweight. When using recently proposed RA sex-specific BMI thresholds1, obesity rates increase in this cohort (53% of females, 80% of males). 17% reported currently smoking. After adjustment for sex, age, and race, baseline disability and pain, and early use of methotrexate (MTX), the odds of achieving sustained remission was significantly lower in patients who smoked and were underweight, overweight or obese (see table), although achieving LDAS by 6 months remains the strongest predictor of sustained remission. Conclusions Overweight and obesity and smoking are common among early RA patients. Normal body weight and non-smoking status were independent predictors of achieving sustained remission after controlling for sociodemographic, disease and treatment characteristics. BMI and smoking should be considered amongst the modifiable lifestyle factors to improve likelihood of optimizing treatment and achieving sustained remission in early RA. References Katz, Patricia et al. “Gender Differences in Assessment of Obesity in Rheumatoid Arthritis.” Arthritis care & research 65.1 (2013): 62–70. Disclosure of Interest S. Goodman: None declared, Y. Ma: None declared, W. Zhang: None declared, E. Schulman: None declared, S. Bartlett: None declared, K. Andersen: None declared, C. Hitchon: None declared, G. Boire: None declared, S. Jamal: None declared, J. C. Thorne: None declared, D. Tin: None declared, E. Keystone: None declared, B. Haraoui: None declared, J. Pope: None declared, V. Bykerk Grant/research support from: The CATCH study was designed and implemented by the investigators and financially supported initially by Amgen Canada Inc. and Pfizer Canada Inc. via an unrestricted research grant since the inception of CATCH. As of 2011, further support was provided by Hoffmann-LaRoche Ltd., UCB Canada Inc., Bristol-Myers Squibb Canada Co., AbbVie Corporation (formerly Abbott Laboratories Ltd.), and Janssen Biotech Inc. (a wholly owned subsidiary of Johnson & Johnson Inc.)
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BackgroundImmune checkpoint inhibitors (ICI) improve overall survival and progression-free survival in many types of malignancies and are the new pillar of cancer treatment[1]. ICIs harness a patient’s own immune system to fight their... more
BackgroundImmune checkpoint inhibitors (ICI) improve overall survival and progression-free survival in many types of malignancies and are the new pillar of cancer treatment[1]. ICIs harness a patient’s own immune system to fight their cancer. However, this activation of the immune system can result in off-target immune-related adverse events (irAEs). One of the most disabling irAE is inflammatory arthritis (ir-IA)[2]affecting up to 7.5% of those treated with ICI[3]. Unlike most irAE which usually resolve within a few months, ir-IA can become chronic and persist even after ICI cessation, requiring long term immunosuppression[4]. The factors associated with chronic ir-IA and its significance regarding tumor outcomes remain largely unknown. With the increasing use of ICI in the adjuvant therapy, it is important to understand predictors and outcomes of chronic ir-IA in order to best counsel patients.ObjectivesTo determine predictors and outcomes of chronic ir-IA in cancer patients expos...
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BackgroundImmune checkpoint inhibitors (ICI) have changed the landscape of treatment for many cancers. However, most cancer clinical trials for ICI excluded patients with pre-existing autoimmune disease (PAD). Efficacy and safety data on... more
BackgroundImmune checkpoint inhibitors (ICI) have changed the landscape of treatment for many cancers. However, most cancer clinical trials for ICI excluded patients with pre-existing autoimmune disease (PAD). Efficacy and safety data on the use of ICI in patients with rheumatic PAD (Rh-PAD) is limited to retrospective case series and reports, and many do not differentiate between Rh-PAD and non-rheumatic PAD. In addition, little is known about optimal use of concurrent immunosuppression and its impact on PAD flares and development of de novo irAE. There is some data that patients on immunosuppression at baseline are at risk for poorer tumor outcomes [1].ObjectivesTo explore the safety and efficacy of ICI in patients with Rh-PAD and to determine if immunosuppression at baseline impacts risk of PAD flare, de-novo irAE and early tumor outcomes using data from the CanRIO prospective cohort.MethodsThe CanRIO cohort includes adult patients with Rh-PAD treated with immune checkpoint inhib...
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BackgroundImmune Checkpoint Inhibitors (ICI) have altered the landscape of cancer therapy. However, toxicities are common and up to 80% of patients will develop immune-related adverse events (irAE), including rheumatic irAEs (Rh-irAE),... more
BackgroundImmune Checkpoint Inhibitors (ICI) have altered the landscape of cancer therapy. However, toxicities are common and up to 80% of patients will develop immune-related adverse events (irAE), including rheumatic irAEs (Rh-irAE), which can often limit their cancer treatment. Our knowledge of clinical manifestations and optimal management of patients with Rh-irAE continues to evolve as these agents are being used to treat a wider variety of cancers. Currently available data is limited to retrospective case series and case reports. There is also scarce data on the use of ICI in patients with pre-existing autoimmune disease (PAD) as these patients are often excluded from clinical trials.ObjectivesTo describe the clinical presentation, management and early outcomes of patients exposed to ICI with Rh-irAE or PAD recruited and followed prospectively from multiple sites across Canada.MethodsAdult patients with Rh-irAE from cancer immunotherapy (CTLA-4, PD-1 or PDL-1 inhibitors) or th...
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Background: Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy by harnessing the immune system to fight cancer. As the indications for ICI continue to expand, their success in advanced stage malignancies is tempered by... more
Background: Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy by harnessing the immune system to fight cancer. As the indications for ICI continue to expand, their success in advanced stage malignancies is tempered by the development of autoimmune toxicities, referred to as immune-related adverse events (irAE). Rheumatic irAE (Rh-irAE), particularly arthralgias and arthritis are common and optimal management remains unknown. Objectives: The Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) is an emerging network of Canadian rheumatologists with an interest in Rh-irAE secondary to ICI. We describe the clinical presentation and management of Rh-irAE associated with ICI in patients seen at 9 CanRIO sites. Methods: Patients presenting with rheumatic symptoms associated with ICI therapy between 2013 and January 2019 at participating CanRIO sites were identified. Cases were stratified based on the presence or absence of pre-existing autoimmune disease...
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Limited data are available on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with preexisting autoimmune diseases (PAD). Retrospective study of patients with PAD referred for rheumatologic evaluation prior to... more
Limited data are available on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with preexisting autoimmune diseases (PAD). Retrospective study of patients with PAD referred for rheumatologic evaluation prior to starting or during immunotherapy between January 2013 and July 2019 from 10 academic sites across Canada. Data were extracted by chart review using a standardized form. Twenty-seven patients with PAD on ICI therapy were identified. The most common PADs were rheumatoid arthritis (30%), psoriasis/psoriatic arthritis (30%), inflammatory bowel disease (IBD, 15%) and axial spondyloarthritis (11%), and the most frequently observed cancers were lung cancer and melanoma. All patients received anti-PD-1 therapies, and 2 received additional sequential anti-CTLA-4 therapy. PAD exacerbations occurred in 52% over a median (IQR) follow-up of 11.0 (6.0–17.5) months, with 14% being severe, 57% requiring corticosteroids, 50% requiring immunosuppression and 14% requiring ICI discontinuation. Flares were generally more frequent and severe in patients who previously required more intensive immunosuppression (i.e., biologics). Flares occurred despite background immunosuppression at the time of ICI initiation. In patients with preexisting psoriasis, IBD and axial spondyloarthritis, rheumatic immune-related adverse events (irAEs), mostly polyarthritis and tenosynovitis, were frequently observed. Tumor progression was not associated with exposure to immunosuppressive drugs before or after ICI initiation and was numerically less frequent in patients with irAEs. PAD exacerbations in the context of ICI treatment are common, although generally mild, and occur despite background immunosuppression. Exacerbations are more frequent and severe in patients on more intensive immunosuppressive therapies pre-immunotherapy.
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ObjectiveTo jointly estimate American College of Rheumatology (ACR50) response (a more commonly reported outcome) and remission (a more clinically relevant outcome) for methotrexate (MTX)‐based treatment options in rheumatoid arthritis... more
ObjectiveTo jointly estimate American College of Rheumatology (ACR50) response (a more commonly reported outcome) and remission (a more clinically relevant outcome) for methotrexate (MTX)‐based treatment options in rheumatoid arthritis (RA).MethodsWe conducted a bivariate network meta‐analysis (NMA) to compare MTX monotherapy and MTX‐based conventional and biologic disease‐modifying antirheumatic drug (DMARD) combinations for RA. The correlation between the outcomes was derived from an incident RA cohort study, whereas the treatment effects were derived from randomized trials in the network of evidence. The analyses were conducted separately for MTX‐naïve and MTX–inadequate response (IR) populations in a Bayesian framework with uninformative priors.ResultsFrom the cohort study, the correlation between ACR50 response and Disease Activity Score 28 remission at 6 months was moderate (Pearson correlation coefficient = 0.58). In the bivariate NMA for MTX‐naïve populations, most combinati...
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ObjectiveTo provide the initial installment of a living guideline that will provide up-to-date guidance on the pharmacological management of patients with rheumatoid arthritis (RA) in Canada.MethodsThe Canadian Rheumatology Association... more
ObjectiveTo provide the initial installment of a living guideline that will provide up-to-date guidance on the pharmacological management of patients with rheumatoid arthritis (RA) in Canada.MethodsThe Canadian Rheumatology Association (CRA) formed a multidisciplinary panel composed of rheumatologists, researchers, methodologists, and patients. In this first installment of our living guideline, the panel developed a recommendation for the tapering of biologic and targeted synthetic disease-modifying antirheumatic drug (b/ts DMARD) therapy in patients in sustained remission using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, including a health equity framework developed for the Canadian RA population. The recommendation was adapted from a living guideline of the Australia & New Zealand Musculoskeletal Clinical Trials Network.ResultsIn people with RA who are in sustained low disease activity or remission for at least 6 months, we suggest offe...
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BackgroundRheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance... more
BackgroundRheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management.MethodsFirst, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed.ResultsThe overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differ...
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Background Interleukin-6 inhibitors reduce mortality in severe COVID-19. British Columbia began using tocilizumab 8 mg/kg (maximum 800 mg) in January 2021 in critically ill patients with COVID-19, but due to drug shortages, decreased... more
Background Interleukin-6 inhibitors reduce mortality in severe COVID-19. British Columbia began using tocilizumab 8 mg/kg (maximum 800 mg) in January 2021 in critically ill patients with COVID-19, but due to drug shortages, decreased dosing to 400 mg IV fixed dose in April 2021. The aims of this study were twofold: to compare physiological responses and clinical outcomes of these two strategies, and examine the cost-effectiveness of treating all patients with 400 mg versus half the patients with 8 mg/kg and the other half without tocilizumab. Methods This was a single-centre, before-after cohort study of critically ill COVID-19 patients treated with tocilizumab, and a control cohort treated with dexamethasone only. Physiological responses and clinical outcomes were compared between patients receiving both doses of tocilizumab and those receiving dexamethasone only. We built a decision tree model to examine cost-effectiveness. Findings 152 patients were included; 40 received tocilizumab 8 mg/kg, 59 received 400 mg and 53 received dexamethasone only. Median CRP fell from 103 mg/L to 5.2 mg/L, 96 mg/L to 6.8 mg/L and from 81.3 mg/L to 48 mg/L in the 8 mg/kg, 400 mg tocilizumab, and dexamethasone only groups, respectively. 28-day mortality was 5% (n=2) vs 8% (n=5) vs 13% (n=7), with no significant difference in all pair-wise comparison. At an assumed willingness-to-pay threshold of $50,000 Canadian per life-year, utilizing 400 mg for all patients rather than 8 mg/kg for half the patients is cost-effective in 51.6% of 10,000 Monte Carlo simulations. Interpretation Both doses of tocilizumab demonstrated comparable reduction of inflammation with similar 28-day mortality. Without consideration of equity, the net monetary benefits of providing 400 mg tocilizumab to all patients are comparable to 8 mg/kg to half the patients. In the context of ongoing drug shortages, fixed-dose 400 mg tocilizumab may be a practical, feasible and economical option. Funding This work was supported by a gift donation from Hsu & Taylor Family to the VGH Foundation, and the Yale Bernard G. Forget Scholarship.
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Background: There are regional disparities in the distribution of Canadian rheumatologists. The objective of this study was to identify factors impacting rheumatology residents’ postgraduate practice decisions to inform Canadian... more
Background: There are regional disparities in the distribution of Canadian rheumatologists. The objective of this study was to identify factors impacting rheumatology residents’ postgraduate practice decisions to inform Canadian Rheumatology Association workforce recommendations. Methods: An online survey was developed, and invitations were sent to all current Canadian rheumatology residents in 2019 (n = 67). Differences between subgroups of respondents were examined using the Pearson χ2 test. Results: A total of 34 of 67 residents completed the survey. Seventy-three percent of residents planned to practice in the same province as their rheumatology training. The majority of residents (80%) ranked proximity to friends and family as the most important factor in planning. Half of participants had exposure to alternative modes of care delivery (e.g. telehealth) during their rheumatology training with fifteen completing a community rheumatology elective (44%). Conclusions: The majority ...
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Supplemental material, Appendix_1_Final for Vaccination Guidelines for Patients With Immune-Mediated Disorders on Immunosuppressive Therapies by Kim A. Papp, Boulos Haraoui, Deepali Kumar, John K. Marshall, Robert Bissonnette, Alain... more
Supplemental material, Appendix_1_Final for Vaccination Guidelines for Patients With Immune-Mediated Disorders on Immunosuppressive Therapies by Kim A. Papp, Boulos Haraoui, Deepali Kumar, John K. Marshall, Robert Bissonnette, Alain Bitton, Brian Bressler, Melinda Gooderham, Vincent Ho, Shahin Jamal, Janet E. Pope, A. Hillary Steinhart, Donald C. Vinh and John Wade in Journal of Cutaneous Medicine and Surgery
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To determine the comparative effectiveness of oral versus subcutaneous methotrexate (MTX) as initial therapy for patients with early rheumatoid arthritis (ERA). Patients with ERA (symptoms ≤1 year) initiating MTX therapy were included... more
To determine the comparative effectiveness of oral versus subcutaneous methotrexate (MTX) as initial therapy for patients with early rheumatoid arthritis (ERA). Patients with ERA (symptoms ≤1 year) initiating MTX therapy were included from a multicentre, prospective cohort study. We compared the effectiveness between starting with oral versus subcutaneous MTX over the first year. Longitudinal multivariable models, adjusted for potential baseline and time-varying confounders, were used to compare treatment changes due to inefficacy or toxicity and treatment efficacy (Disease Activity Score-28 (DAS-28), DAS-28 remission and Health Assessment Questionnaire-Disability Index (HAQ-DI)). 666 patients were included (417 oral MTX, 249 subcutaneous MTX). Patients prescribed subcutaneous MTX were prescribed a higher dose of MTX (mean dose over first three months 22.3 mg vs 17.2 mg/week). At 1 year, 49% of patients initially treated with subcutaneous MTX had changed treatment compared with 77% ...
Research Interests: Immunology, Rheumatoid Arthritis, Medicine, Multivariate Analysis, Prospective studies, and 14 moreHumans, Internal Medicine, Female, Male, Clinical Sciences, Middle Aged, Longitudinal Studies, Adult, Public health systems and services research, Time Factors, Methotrexate, Comparative Effectiveness Research, Severity of Illness Index, and Treatment Failure
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Objective.To determine site variation by comparing outcomes across sites in an early rheumatoid arthritis cohort.Methods.Sites from the Canadian Early Arthritis Cohort database with at least 40 patients were studied. Comparisons were made... more
Objective.To determine site variation by comparing outcomes across sites in an early rheumatoid arthritis cohort.Methods.Sites from the Canadian Early Arthritis Cohort database with at least 40 patients were studied. Comparisons were made among sites in change in 28-joint Disease Activity Score (DAS28), proportion of patients in DAS28 remission, and treatment strategies.Results.The study included 1138 baseline patients at 8 sites, with baseline (SD) age 52 years (16.9); 72% women; 23% erosions; 54% ever smokers; 51% rheumatoid factor-positive; 37% anticitrullinated protein antibody-positive; disease duration 187 (203) days; DAS28 4.5 (1.4). Site had an effect on outcomes when adjusting for confounders. At 6 and 12 months, sites B and H, the 2 largest sites, had the best changes in DAS28 (−1.82 and −2.09, respectively, at 6 mos, and −2.27 for both at 12 mos; p < 0.001). Site H had the most patients in DAS28 remission at 6 months [64.5% compared to other sites that had from 34.1% t...
Research Interests: Rheumatology, Immunology, Treatment Outcome, Rheumatoid Arthritis, Medicine, and 15 moreCanada, Humans, Internal Medicine, Female, Male, Cohort, Clinical Sciences, Middle Aged, Adult, Public health systems and services research, Methotrexate, Combination drug therapy, Disease Progression, Standard of Care, and Severity of Illness Index
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... A subgroup reviewed the literature on innovative interventions for improving arthritis care (The Manpower and Model of Care Theme; co-leaders: Drs. Elizabeth Badley, David Hawkins, Linda Li, and Dianne Mosher; members: Drs. ...
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Immune checkpoint inhibitors have revolutionized cancer therapy by blocking inhibitory pathways of the immune system to fight cancer cells. Their use is often limited by the development of autoimmune toxicities, which can affect multiple... more
Immune checkpoint inhibitors have revolutionized cancer therapy by blocking inhibitory pathways of the immune system to fight cancer cells. Their use is often limited by the development of autoimmune toxicities, which can affect multiple organ systems and are referred to as immune-related adverse events (irAE). Among these are rheumatologic irAE, including inflammatory arthritis, myositis, vasculitis, and others. Rheumatologic irAE seem to be different from irAE in other organs and from traditional autoimmune diseases in that they can occur early or have delayed onset, and can persist chronically, even after cancer therapy is terminated. Because immune checkpoint inhibitors are increasingly used for many types of cancer, it is important for oncologists and rheumatologists to recognize and manage toxicities early. In this review, we discuss currently approved immune checkpoint inhibitors and their mechanisms of action and systemic toxicities, with a focus on the management and effect...
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Background Video review processes for evaluation and coaching are often incorporated into medical education as a means to accurately capture physician-patient interactions. Compared to direct observation they offer the advantage of... more
Background Video review processes for evaluation and coaching are often incorporated into medical education as a means to accurately capture physician-patient interactions. Compared to direct observation they offer the advantage of overcoming many logistical challenges. However, the suitability and viability of using video-based peer consultations for professional development requires further investigation. This study aims to explore the acceptability and feasibility of video-based peer feedback to support professional development and quality improvement in patient care. Methods Five rheumatologists each provided four videos of patient consultations. Peers evaluated the videos using five-point scales, providing annotations in the video recordings, and offering recommendations. The rheumatologists reviewed the videos of their own four patient interactions along with the feedback. They were asked to document if they would make practice changes based on the feedback. Focus groups were ...
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Background Rheumatic immune-related adverse events (irAEs) are increasingly recognized musculoskeletal manifestations in cancer patients receiving immune checkpoint targeted immunotherapy. Since they represent a spectrum of new clinical... more
Background Rheumatic immune-related adverse events (irAEs) are increasingly recognized musculoskeletal manifestations in cancer patients receiving immune checkpoint targeted immunotherapy. Since they represent a spectrum of new clinical entities and a robust evidence base is lacking, a task force was convened to harmonize expert consensus regarding their identification and management due to the lack of dedicated clinical trials. Our aim was to develop EULAR recommendations for the diagnosis and the management of rheumatic irAEs due to cancer immunotherapy, based on literature and expert opinion. Methods Recommendations were developed according to the 2014 EULAR Standard Operating Procedures. The task force consisted of 19 clinical experts from Europe and North America (14 rheumatologists, 2 internists and 3 oncologists), 1 clinical epidemiologist, 1 allied health professional and 2 patient representatives. During the first meeting, the group defined the focus of the task force, the ...
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Abstract Isolated pulmonary capillaritis (IPC) is a rare autoimmune cause of diffuse alveolar haemorrhage (DAH), diagnosed by histopathological evidence of lung capillaritis in the absence of systemic vasculitis. Only 17 cases of IPC are... more
Abstract Isolated pulmonary capillaritis (IPC) is a rare autoimmune cause of diffuse alveolar haemorrhage (DAH), diagnosed by histopathological evidence of lung capillaritis in the absence of systemic vasculitis. Only 17 cases of IPC are described in the literature to date. Given its rarity, treatments reported for these cases are largely extrapolated from anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV). Here we describe an additional case of IPC refractory to cyclophosphamide and azathioprine, which was rescued by rituximab.
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Background:Patients with immune-mediated diseases on immunosuppressive therapies have more infectious episodes than healthy individuals, yet vaccination practices by physicians for this patient population remain suboptimal.Objectives:To... more
Background:Patients with immune-mediated diseases on immunosuppressive therapies have more infectious episodes than healthy individuals, yet vaccination practices by physicians for this patient population remain suboptimal.Objectives:To evaluate the safety and efficacy of vaccines in individuals exposed to immunosuppressive therapies and provide evidence-based clinical practice recommendations.Methods:A literature search for vaccination safety and efficacy in patients on immunosuppressive therapies (2009-2017) was conducted. Results were assessed using the Grading of Recommendation, Assessment, Development, and Evaluation system.Results:Several immunosuppressive therapies attenuate vaccine response. Thus, vaccines should be administered before treatment whenever feasible. Inactivated vaccines can be administered without treatment discontinuation. Similarly, evidence suggests that the live zoster vaccine is safe and effective while on select immunosuppressive therapy, although use of...
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Obesity is implicated in RA development, severity, outcomes and treatment response. We estimated the independent effects of overweight and obesity on ability to achieve sustained remission (sREM) in the three years following RA diagnosis.... more
Obesity is implicated in RA development, severity, outcomes and treatment response. We estimated the independent effects of overweight and obesity on ability to achieve sustained remission (sREM) in the three years following RA diagnosis. Data were from the Canadian Early Arthritis Cohort, a multicenter observational trial of ERA patients treated by rheumatologists using guideline-based care. sREM was defined as DAS28 <2.6 for two consecutive visits. Patients were stratified by BMI (healthy [18.5-24.9]; overweight [25-29.9]; and obese [≥30]). Cox regression was used to estimate the effect of BMI category on probability of achieving sREM over the first 3 years, controlling for age, sex, race, education, RA duration, smoking status, comorbidities, baseline DAS28, HAQ-DI, CRP, and initial treatment. Of 982 patients, 315 (32%) had a healthy BMI, 343 (35%) were overweight, and 324 (33%) were obese; 355 (36%) achieved sREM within 3 years. Initial treatment did not differ by BMI categor...
Research Interests:
Research Interests: Rheumatology, Immunology, Rheumatoid Arthritis, Canada, Prospective studies, and 14 moreHumans, Hypertension, Female, Male, Cyclic peptides, Incidence, Risk factors, Clinical Sciences, Middle Aged, Public health systems and services research, Analysis of Variance, Cardiovascular Diseases, Risk Factors, and Autoantibodies
The 28-Joint Disease Activity Score (DAS28) using C-reactive protein (CRP) and DAS28 using erythrocyte sedimentation rate (DAS28-ESR) may not be interchangeable. We sought to compare and estimate optimal thresholds for the DA28-CRP for... more
The 28-Joint Disease Activity Score (DAS28) using C-reactive protein (CRP) and DAS28 using erythrocyte sedimentation rate (DAS28-ESR) may not be interchangeable. We sought to compare and estimate optimal thresholds for the DA28-CRP for use in early rheumatoid arthritis (ERA). Patients from the Canadian Early Arthritis Cohort with baseline and 12 months' data for both DAS28-ESR and DAS28-CRP were examined for correlations and differences between DAS28-CRP and DAS28-ESR across their range of values. Receiver operating characteristic analysis identified thresholds for DAS28-CRP that best corresponded to established thresholds for the DAS28-ESR using the total sample, then stratified by age and sex. Agreement between DAS28-CRP and DAS28-ESR thresholds was assessed with the kappa statistic. The sample included 995 patients with mean (SD) age of 53.7 (14.5) years, 5.8 (2.9) months of symptom duration and 74% were female. DAS28-CRP and DAS28-ESR scores were highly correlated (r= 0.92, ...