Shahin Jamal - Academia.edu (original) (raw)

Papers by Shahin Jamal

Research paper thumbnail of Expanding Medical Marijuana Access in Canada: Considerations for the Rheumatologist

The Journal of Rheumatology, Sep 1, 2014

Research paper thumbnail of An evidence-informed, integrated framework for rheumatoid arthritis care

Arthritis & Rheumatism, Aug 15, 2008

... A subgroup reviewed the literature on innovative interventions for improving arthritis care (... more ... 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. ...

Research paper thumbnail of Factors influencing rheumatology residents’ decision on future practice location Facteurs influençant le choix du futur lieu d’exercice chez les résidents en rhumatologie

Canadian medical education journal, Dec 21, 2020

Background: There are regional disparities in the distribution of Canadian rheumatologists. The o... 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. e63 Canadian Medical Education Journal Factors influencing rheumatology residents' decision on future practice location Facteurs influençant le choix du futur lieu d'exercice chez les résidents en rhumatologie

Research paper thumbnail of Time to Treatment for New Patients with Rheumatoid Arthritis in a Major Metropolitan City

The Journal of Rheumatology, May 15, 2011

To determine the proportion of patients with rheumatoid arthritis (RA) seen by rheumatologists an... more To determine the proportion of patients with rheumatoid arthritis (RA) seen by rheumatologists and treated with disease-modifying antirheumatic drugs (DMARD) within 3 months of symptom onset, to determine where treatment delays occur, and to identify contributing factors. Methods. A retrospective cohort study in which adult patients with RA, diagnosed between January 1, 2003, and May 31, 2006, were recruited from rheumatologists' offices to participate in a telephone survey and chart review. The percentage treated with DMARD within 3 months of symptom onset was determined, along with median times for delay. Factors contributing to the delay were explored using multivariable logistic regression. Results. Our study included 204 patients. Within 3 months of symptoms, 22.6% (95% CI 16.8%, 28.3%) received DMARD and within 6 months, 47.6% (95% CI 40.7%, 54.4%). The median time from symptom onset to DMARD was 6.4 months [interquartile range (IQR) 3.3, 12.0] with a median time from RA diagnosis by a rheumatologist to DMARD of 0.0 months (IQR 0.0, 1.0). Higher baseline swollen joint counts resulted in earlier treatment. Age, sex, education, comorbidity, rheumatologist practice type, and years since the physician's graduation did not affect time to treatment. Conclusion. Fewer than 25% of patients referred to rheumatologists were treated within 3 months of symptom onset. Identification of inflammatory arthritis and referral to rheumatologists are the key factors in timely care, because once patients are seen there is no delay to treatment. Future resources should be focused on development and evaluation of interventions to facilitate rapid triage, referral, and assessment by a rheumatologist.

Research paper thumbnail of Factors influencing rheumatology residents’ decision on future practice location

Canadian medical education journal, Dec 21, 2020

Background: There are regional disparities in the distribution of Canadian rheumatologists. The o... 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. e63 Canadian Medical Education Journal Factors influencing rheumatology residents' decision on future practice location Facteurs influençant le choix du futur lieu d'exercice chez les résidents en rhumatologie

Research paper thumbnail of Soluble interleukin-6 receptor in the COVID-19 cytokine storm syndrome

Cell reports medicine, May 1, 2021

Data suggest that interleukin (IL)-6 blockade could reduce mortality in severe COVID-19, yet IL-6... more Data suggest that interleukin (IL)-6 blockade could reduce mortality in severe COVID-19, yet IL-6 is only modestly elevated in most patients. Chen et al. describe the role of soluble interleukin-6 receptor (sIL-6R) in IL-6 trans-signaling and how understanding the IL-6:sIL-6R axis might help define and treat COVID-19 cytokine storm syndrome.

Research paper thumbnail of Biologic Therapy for Systemic Sclerosis: A Systematic Review

The Journal of Rheumatology, Nov 1, 2010

Biologic agents are increasingly used in the rheumatic diseases. Their role in patients with syst... more Biologic agents are increasingly used in the rheumatic diseases. Their role in patients with systemic sclerosis (SSc) is uncertain. Our aim was to evaluate the effectiveness and safety of biologic agents in SSc. We review the evidence for the use of biologic agents to improve inflammatory arthritis, disability, and skin score, and we review adverse effects with biologic agents in patients with SSc. Methods. A systematic literature review was performed to identify studies evaluating the use of biologic agents in SSc. Medline, Embase, CINAHL, and Cochrane Database of Systematic Reviews were searched. A standardized abstraction form was used to extract biologic agent, study design, sample size, treatment effect, and adverse effects. Results. A total of 23 studies from 1413 citations were evaluated. Three studies evaluated infliximab, 3 evaluated etanercept, 3 evaluated antithymocyte globulin, 3 evaluated imatinib, 6 evaluated rituximab, and 1 study each evaluated interferon-g (IFN-g), IFN-a, relaxin, delipidated, deglycolipidated Mycobacterium vaccae, human anti-transforming growth factor ß1 antibody, and oral type I collagen. Studies of etanercept and infliximab suggest improvements in inflammatory arthritis and Health Assessment Questionnaire Disability Index (HAQ-DI). None of the other biologic agents demonstrated reproducible, statistically significant improvements in joint count, HAQ-DI, or skin score. Conclusion. Anti-tumor necrosis factor-a agents may improve inflammatory arthritis and disability in SSc. The effect on skin score is uncertain. Adequately powered trials are needed to evaluate efficacy, and longitudinal studies are needed to evaluate longterm safety of these agents in SSc.

Research paper thumbnail of Internet health scams—Developing a taxonomy and risk‐of‐deception assessment tool

Health & Social Care in the Community, 2018

Belloni, & Sassi, 2014) and with it there has been a parallel rise in Internet Health Scams (IHS)... more Belloni, & Sassi, 2014) and with it there has been a parallel rise in Internet Health Scams (IHS). Nostrum sales-when products are sold based on exaggerated claims or falsehoods-and the use of mass media to facilitate scams are not new phenomena. Although deceptive marketing dates back to before the last century (Offit, 2013; Rance, 2013, p. 121), the broad availability of the Internet (particularly email, social media, and Web use) over the past two decades has facilitated an increasing number of illicit opportunities for marketing health scams (Caulfield,

Research paper thumbnail of IgG4-related prostatitis manifesting as urinary obstruction in a 28-year-old male

BMC Urology, Mar 11, 2022

Background: Immunoglobulin G4-related disease (IgG4-RD) is a systemic lymphoproliferative disorde... more Background: Immunoglobulin G4-related disease (IgG4-RD) is a systemic lymphoproliferative disorder characterized by elevated serum IgG4 levels and tumefactive lesions that can involve nearly every organ system. Involvement of the prostate is rare but has been reported in limited cases. Case presentation: A 28-year-old man of Asian descent with a history of sinusitis and priapism presented to hospital with rigors and voiding symptoms. He was diagnosed with IgG4-RD one month prior to presentation, following pathological analysis of a submandibular mass that demonstrated chronic sclerosing sialadenitis. On presentation, white blood cell count, C-reactive protein, and prostate serum antigen levels were all within normal limits. Examination was notable for a large, firm prostate, and a foley catheter was inserted. Contrast CT of the abdomen was unremarkable. Further workup revealed elevated serum IgG4 levels (9.22 g/L) and he was subsequently started on prednisone 35 mg daily. Imaging to screen for systemic IgG4-RD involvement demonstrated paravertebral soft tissue involvement and he was given rituximab 1000 mg IV × 2 doses. MRI revealed diffuse prostatitis. Five days after starting prednisone and one day after his first dose of rituximab, he successfully passed trial of void and was discharged home. Conclusions: IgG4-related prostatitis is a rare and underrecognized manifestation of IgG4-RD. Our case highlights the need to consider IgG4-related prostatitis as an etiology of urinary obstruction in young individuals. Resolution of symptoms following treatment with steroids may be diagnostic of IgG4-related prostatitis, and may potentially avoid the need for invasive diagnostic procedures such as prostate biopsy.

Research paper thumbnail of The comparative effectiveness of oral versus subcutaneous methotrexate for the treatment of early rheumatoid arthritis

Annals of the Rheumatic Diseases, May 15, 2015

To determine the comparative effectiveness of oral versus subcutaneous methotrexate (MTX) as init... 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 paper thumbnail of Identification of outcome domains in immune checkpoint inhibitor-induced inflammatory arthritis and polymyalgia rheumatica: A scoping review by the OMERACT irAE working group

Seminars in Arthritis and Rheumatism, Feb 1, 2023

Research paper thumbnail of Validation of Self-Reported Cardiovascular Disease and Associated Co- Morbidities in a Large Canadian Cohort of Early Inflammatory Arthritis

Rheumatology, 2017

Objective: Cardiovascular disease (CVD) and risk factors for CVD (smoking, hypertension, dyslipid... more Objective: Cardiovascular disease (CVD) and risk factors for CVD (smoking, hypertension, dyslipidemia and diabetes) are commonly associated with Rheumatoid Arthritis (RA). We aimed to determine the validity of selfreported CVD events and risk factors in the Canadian Early Arthritis Cohort (CATCH). Methods: CATCH is a multicenter inception cohort of patients with early RA. Various co-morbidities and pharmacologic therapies are self-reported at baseline and at each follow-up visit. Using a randomly selected subgroup of subjects enrolled in CATCH from one representative site, we performed a detailed review of their complete medical record to identify diagnoses of CVD events, risk factors and drug therapies. The validity of selfreported variables was determined using the Cohen's kappa statistic. Results: The validation subgroup (N=141) was similar to the entire CATCH population (N=2626) with respect to baseline demographics and RA disease characteristics. There was very good agreement between self-report and the medical record for cardiovascular or cerebrovascular events (kappa=0.66), as well as for hypertension and diabetes (kappa=0.70 and 0.81, respectively). Subjects tended to under-report dyslipidemia and the reporting of lipid-lowering and antiplatelet/anticoagulant agents was inaccurate compared to the medical record. Conclusion: Self-reported cardiovascular disease, hypertension and diabetes was representative of the medical record suggesting that these self-reported variables are valuable for future studies of this early RA population.

Research paper thumbnail of OP0173 How Much of A Barrier Is Excess Weight and Smoking for Achieving Sustained Remission in Early RA? Results from The Canadian Early Arthritis Cohort

Annals of the Rheumatic Diseases, Jun 1, 2016

Background: Fatigue is common in early RA(ERA) and though some patients experience improvement in... more Background: Fatigue is common in early RA(ERA) and though some patients experience improvement in fatigue when disease is well controlled, others experience persistent fatigue associated with work disability, poor QOL, and depression. Objectives: To compare patterns and predictors of improved vs. persistent fatigue in the first year of ERA. Methods: Data were from ERA patients (symptoms <1 year) enrolled in the Canadian Early Arthritis Cohort (CATCH) from 01-2007 to 03-2017. All met ACR1987 or 2010 ACR/EULAR criteria, had active disease, were on DMARDS, and complete fatigue (0-10) data over ! 12 months. Patients were classified at baseline with low (<4) or high (!4) fatigue; high fatigue patients were categorized at 12-months as improved (# !2) or persistent (# <2). Multivariable logistic regression was used to identify predictors of improved vs. persistent fatigue at 12 months in those with high baseline fatigue. Results: The 1002 pts were mostly white (81%), female (71%), with a mean (SD) age of 54 (15); 32% were obese. 70% had high fatigue at baseline; these patients were more obese, had OA/backpain, poor sleep, depression, major stress, and higher disease activity (Table 1). Among those with initial high fatigue, 30% had persistent fatigue at 12 months and was associated with obesity, comorbidities, FM, longer symptom duration, and slightly lower baseline fatigue.

Research paper thumbnail of SAT0055 Treatment Response To Conventional Disease Modifying Anti-Rheumatic Drugs (Dmards) and Biologics in Seropositive and Seronegative Patients with Early Rheumatoid Arthritis: Results from Catch (Canadian Early Arthritis Cohort)

Annals of the Rheumatic Diseases, Jun 1, 2016

NCT01197755). Patients who did not achieve ACR20 at week 12 were given active drug and were consi... more NCT01197755). Patients who did not achieve ACR20 at week 12 were given active drug and were considered escapers. Radiographic progression was assessed by increase in JSN, erosion (ERN) or modified total sharp score (mTSS) after 24 weeks. Only 270 patients had radiographic assessment at both baseline and at 24 weeks. C1M was assessed in fasting serum at baseline (BL). One-way ANOVA was used to assess differences in BL demographics. Associations between BL demographics were investigated by Spearman's correlation. Multiple regression included age group, gender, disease duration, BMI, CRP and BL radiographic status. Non-normalized data was log-transformed. Results: BL demographics of the 3 studies were comparable. 36% of patients were escapers, having BL elevated levels of C1M, CRP and disease activity compared to non-escapers (p=0.03, p<0.0001, p=0.006). 20% of all patients had radiographic progression by JSN, 24% by ERN and 31% by mTSS. BL CRP was significantly elevated in progressors compared to non-progressors (JSN p=0.02, mTSS p=0.005, ERN p=0.005). ERN progressors had a significantly increased level of C1M than non-progressors (p=0.02). JSN only progressors had significant increases in BL radiographic status compared to non-progressors (JSN p=0.003, mTSS p=0.007, ERN p=0.03). At BL there was an association between C1M and radiographic status (JSN rho=0.14, mTSS rho=0.14, ERN rho=0.13,) and disease activity (DAS28 rho=0.44). In multiple regression the effect size β of C1M alone was-0.25, 0.90 and 1.18 for the association with the 24 week change in radiographic progression as determined by JSN, mTSS and ERN, respectively. Only for ERN the effect size reached statistical significance (p=0.0008). The beta value describes the effect of C1M on predicting the radiographic progression. The effect size decreased for JSN when adjusted for CRP (β=-0.68), but for both mTSS and ERN the effect was eliminated. When the other confounders were included the effect size decreased even further for JSN (β=-0.70). Conclusions: In this study we found that BL C1M was associated with structural status and disease activity and that BL C1M was a predictor of radiographic progression (JSN) after 24 weeks when adjusted for confounders. Secondly, escapers had higher level of C1M, CRP and disease activity indication a worse disease stage in escapers at baseline. This study provides supports C1M as an important emerging biomarker of progression in RA. References: [1]

Research paper thumbnail of THU0149 Does Methotrexate Lower Serum Uric Acid Levels? Data from the Catch Cohort

Annals of the Rheumatic Diseases, Jun 1, 2015

Background Methotrexate is the cornerstone DMARD in the treatment of rheumatoid arthritis. The ex... 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

Research paper thumbnail of THU0169 Persistence of Tofacitinib in The Treatment of Rheumatoid Arthritis in Open-Label, Long-Term Extension Studies up To 7 Years

Annals of the Rheumatic Diseases, Jun 1, 2016

Background Tofacitinib is an oral JAK inhibitor for treatment of rheumatoid arthritis (RA). Open-... 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

Research paper thumbnail of OP0178 Body Mass Index is an Independent Risk Factor for not Achieving Sustained Remission in Early Rheumatoid Arthritis: Results from the Catch Observational Study

Annals of the Rheumatic Diseases, Jun 1, 2015

Background Little is known about how lifestyle factors contribute to treatment response in early ... 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.)

Research paper thumbnail of Real-World Tocilizumab Use in Patients with Rheumatoid Arthritis in Canada: 12-Month Results From an Observational, Noninterventional Study

Rheumatology and therapy, Oct 28, 2018

Introduction: This study was conducted to observe patterns of use of the interleukin-6 receptor-a... more Introduction: This study was conducted to observe patterns of use of the interleukin-6 receptor-alpha inhibitor tocilizumab in routine clinical practice in patients with rheumatoid arthritis (RA). Methods: This was a 12-month noninterventional, observational study in adult patients with RA who initiated tocilizumab in routine practice in Canada according to the local product monograph. The primary end point was the proportion of patients receiving tocilizumab at 6 months. Secondary end points were treatment patterns, effectiveness, and safety of tocilizumab over 12 months. Results: Of 200 patients who initiated tocilizumab (91.0% at 8 mg/kg), 67 (33.5%) received tocilizumab monotherapy and 133 (66.5%) received tocilizumab combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Kaplan-Meier analysis estimated that 85% (95% CI 74-92%) of monotherapy and 89% (95% CI 82-93%) of combination therapy patients continued to receive tocilizumab at 6 months (log-rank p = 0.0888). During the observation period, 12 (17.9%) monotherapy and 27 (20.3%) combination therapy patients withdrew from the study. At month 12, 58.5% in the monotherapy group and 59.3% in the combination therapy group achieved Disease Activity Score at 28 joints remission (B 2.6), 25.6% and 24.7% achieved Simplified Disease Activity Index remission (B 3.3), and 18.2% and 22.3% achieved Clinical Disease Activity Index remission (B 2.8), respectively. Rates of serious adverse events and serious infections were found in 29.6/100 patient-years (PY) and 3.1/ 100 PY, respectively, for monotherapy and 19.2/ 100 PY and 4.8/100 PY, respectively, for combination therapy.

Research paper thumbnail of POS1567 OUTCOMES and Predictors of Chronic Immune Checkpoint Inhibitor Induced Inflammatory Arthritis: Data from the Canadian Research Group of Rheumatology in Immuno-Oncology (Canrio) Retrospective Cohort

Annals of the Rheumatic Diseases

BackgroundImmune checkpoint inhibitors (ICI) improve overall survival and progression-free surviv... 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...

Research paper thumbnail of AB1768-HPR SAFETY and Efficacy of Immune Checkpoint Inhibitors in Patients with Rheumatic Autoimmune Disease: Experience from the Canadian Research Group of Rheumatology in Immuno-Oncology (Canrio)

Health Professionals in Rheumatology Abstracts

BackgroundImmune checkpoint inhibitors (ICI) have changed the landscape of treatment for many can... 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...

Research paper thumbnail of Expanding Medical Marijuana Access in Canada: Considerations for the Rheumatologist

The Journal of Rheumatology, Sep 1, 2014

Research paper thumbnail of An evidence-informed, integrated framework for rheumatoid arthritis care

Arthritis & Rheumatism, Aug 15, 2008

... A subgroup reviewed the literature on innovative interventions for improving arthritis care (... more ... 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. ...

Research paper thumbnail of Factors influencing rheumatology residents’ decision on future practice location Facteurs influençant le choix du futur lieu d’exercice chez les résidents en rhumatologie

Canadian medical education journal, Dec 21, 2020

Background: There are regional disparities in the distribution of Canadian rheumatologists. The o... 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. e63 Canadian Medical Education Journal Factors influencing rheumatology residents' decision on future practice location Facteurs influençant le choix du futur lieu d'exercice chez les résidents en rhumatologie

Research paper thumbnail of Time to Treatment for New Patients with Rheumatoid Arthritis in a Major Metropolitan City

The Journal of Rheumatology, May 15, 2011

To determine the proportion of patients with rheumatoid arthritis (RA) seen by rheumatologists an... more To determine the proportion of patients with rheumatoid arthritis (RA) seen by rheumatologists and treated with disease-modifying antirheumatic drugs (DMARD) within 3 months of symptom onset, to determine where treatment delays occur, and to identify contributing factors. Methods. A retrospective cohort study in which adult patients with RA, diagnosed between January 1, 2003, and May 31, 2006, were recruited from rheumatologists' offices to participate in a telephone survey and chart review. The percentage treated with DMARD within 3 months of symptom onset was determined, along with median times for delay. Factors contributing to the delay were explored using multivariable logistic regression. Results. Our study included 204 patients. Within 3 months of symptoms, 22.6% (95% CI 16.8%, 28.3%) received DMARD and within 6 months, 47.6% (95% CI 40.7%, 54.4%). The median time from symptom onset to DMARD was 6.4 months [interquartile range (IQR) 3.3, 12.0] with a median time from RA diagnosis by a rheumatologist to DMARD of 0.0 months (IQR 0.0, 1.0). Higher baseline swollen joint counts resulted in earlier treatment. Age, sex, education, comorbidity, rheumatologist practice type, and years since the physician's graduation did not affect time to treatment. Conclusion. Fewer than 25% of patients referred to rheumatologists were treated within 3 months of symptom onset. Identification of inflammatory arthritis and referral to rheumatologists are the key factors in timely care, because once patients are seen there is no delay to treatment. Future resources should be focused on development and evaluation of interventions to facilitate rapid triage, referral, and assessment by a rheumatologist.

Research paper thumbnail of Factors influencing rheumatology residents’ decision on future practice location

Canadian medical education journal, Dec 21, 2020

Background: There are regional disparities in the distribution of Canadian rheumatologists. The o... 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. e63 Canadian Medical Education Journal Factors influencing rheumatology residents' decision on future practice location Facteurs influençant le choix du futur lieu d'exercice chez les résidents en rhumatologie

Research paper thumbnail of Soluble interleukin-6 receptor in the COVID-19 cytokine storm syndrome

Cell reports medicine, May 1, 2021

Data suggest that interleukin (IL)-6 blockade could reduce mortality in severe COVID-19, yet IL-6... more Data suggest that interleukin (IL)-6 blockade could reduce mortality in severe COVID-19, yet IL-6 is only modestly elevated in most patients. Chen et al. describe the role of soluble interleukin-6 receptor (sIL-6R) in IL-6 trans-signaling and how understanding the IL-6:sIL-6R axis might help define and treat COVID-19 cytokine storm syndrome.

Research paper thumbnail of Biologic Therapy for Systemic Sclerosis: A Systematic Review

The Journal of Rheumatology, Nov 1, 2010

Biologic agents are increasingly used in the rheumatic diseases. Their role in patients with syst... more Biologic agents are increasingly used in the rheumatic diseases. Their role in patients with systemic sclerosis (SSc) is uncertain. Our aim was to evaluate the effectiveness and safety of biologic agents in SSc. We review the evidence for the use of biologic agents to improve inflammatory arthritis, disability, and skin score, and we review adverse effects with biologic agents in patients with SSc. Methods. A systematic literature review was performed to identify studies evaluating the use of biologic agents in SSc. Medline, Embase, CINAHL, and Cochrane Database of Systematic Reviews were searched. A standardized abstraction form was used to extract biologic agent, study design, sample size, treatment effect, and adverse effects. Results. A total of 23 studies from 1413 citations were evaluated. Three studies evaluated infliximab, 3 evaluated etanercept, 3 evaluated antithymocyte globulin, 3 evaluated imatinib, 6 evaluated rituximab, and 1 study each evaluated interferon-g (IFN-g), IFN-a, relaxin, delipidated, deglycolipidated Mycobacterium vaccae, human anti-transforming growth factor ß1 antibody, and oral type I collagen. Studies of etanercept and infliximab suggest improvements in inflammatory arthritis and Health Assessment Questionnaire Disability Index (HAQ-DI). None of the other biologic agents demonstrated reproducible, statistically significant improvements in joint count, HAQ-DI, or skin score. Conclusion. Anti-tumor necrosis factor-a agents may improve inflammatory arthritis and disability in SSc. The effect on skin score is uncertain. Adequately powered trials are needed to evaluate efficacy, and longitudinal studies are needed to evaluate longterm safety of these agents in SSc.

Research paper thumbnail of Internet health scams—Developing a taxonomy and risk‐of‐deception assessment tool

Health & Social Care in the Community, 2018

Belloni, & Sassi, 2014) and with it there has been a parallel rise in Internet Health Scams (IHS)... more Belloni, & Sassi, 2014) and with it there has been a parallel rise in Internet Health Scams (IHS). Nostrum sales-when products are sold based on exaggerated claims or falsehoods-and the use of mass media to facilitate scams are not new phenomena. Although deceptive marketing dates back to before the last century (Offit, 2013; Rance, 2013, p. 121), the broad availability of the Internet (particularly email, social media, and Web use) over the past two decades has facilitated an increasing number of illicit opportunities for marketing health scams (Caulfield,

Research paper thumbnail of IgG4-related prostatitis manifesting as urinary obstruction in a 28-year-old male

BMC Urology, Mar 11, 2022

Background: Immunoglobulin G4-related disease (IgG4-RD) is a systemic lymphoproliferative disorde... more Background: Immunoglobulin G4-related disease (IgG4-RD) is a systemic lymphoproliferative disorder characterized by elevated serum IgG4 levels and tumefactive lesions that can involve nearly every organ system. Involvement of the prostate is rare but has been reported in limited cases. Case presentation: A 28-year-old man of Asian descent with a history of sinusitis and priapism presented to hospital with rigors and voiding symptoms. He was diagnosed with IgG4-RD one month prior to presentation, following pathological analysis of a submandibular mass that demonstrated chronic sclerosing sialadenitis. On presentation, white blood cell count, C-reactive protein, and prostate serum antigen levels were all within normal limits. Examination was notable for a large, firm prostate, and a foley catheter was inserted. Contrast CT of the abdomen was unremarkable. Further workup revealed elevated serum IgG4 levels (9.22 g/L) and he was subsequently started on prednisone 35 mg daily. Imaging to screen for systemic IgG4-RD involvement demonstrated paravertebral soft tissue involvement and he was given rituximab 1000 mg IV × 2 doses. MRI revealed diffuse prostatitis. Five days after starting prednisone and one day after his first dose of rituximab, he successfully passed trial of void and was discharged home. Conclusions: IgG4-related prostatitis is a rare and underrecognized manifestation of IgG4-RD. Our case highlights the need to consider IgG4-related prostatitis as an etiology of urinary obstruction in young individuals. Resolution of symptoms following treatment with steroids may be diagnostic of IgG4-related prostatitis, and may potentially avoid the need for invasive diagnostic procedures such as prostate biopsy.

Research paper thumbnail of The comparative effectiveness of oral versus subcutaneous methotrexate for the treatment of early rheumatoid arthritis

Annals of the Rheumatic Diseases, May 15, 2015

To determine the comparative effectiveness of oral versus subcutaneous methotrexate (MTX) as init... 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 paper thumbnail of Identification of outcome domains in immune checkpoint inhibitor-induced inflammatory arthritis and polymyalgia rheumatica: A scoping review by the OMERACT irAE working group

Seminars in Arthritis and Rheumatism, Feb 1, 2023

Research paper thumbnail of Validation of Self-Reported Cardiovascular Disease and Associated Co- Morbidities in a Large Canadian Cohort of Early Inflammatory Arthritis

Rheumatology, 2017

Objective: Cardiovascular disease (CVD) and risk factors for CVD (smoking, hypertension, dyslipid... more Objective: Cardiovascular disease (CVD) and risk factors for CVD (smoking, hypertension, dyslipidemia and diabetes) are commonly associated with Rheumatoid Arthritis (RA). We aimed to determine the validity of selfreported CVD events and risk factors in the Canadian Early Arthritis Cohort (CATCH). Methods: CATCH is a multicenter inception cohort of patients with early RA. Various co-morbidities and pharmacologic therapies are self-reported at baseline and at each follow-up visit. Using a randomly selected subgroup of subjects enrolled in CATCH from one representative site, we performed a detailed review of their complete medical record to identify diagnoses of CVD events, risk factors and drug therapies. The validity of selfreported variables was determined using the Cohen's kappa statistic. Results: The validation subgroup (N=141) was similar to the entire CATCH population (N=2626) with respect to baseline demographics and RA disease characteristics. There was very good agreement between self-report and the medical record for cardiovascular or cerebrovascular events (kappa=0.66), as well as for hypertension and diabetes (kappa=0.70 and 0.81, respectively). Subjects tended to under-report dyslipidemia and the reporting of lipid-lowering and antiplatelet/anticoagulant agents was inaccurate compared to the medical record. Conclusion: Self-reported cardiovascular disease, hypertension and diabetes was representative of the medical record suggesting that these self-reported variables are valuable for future studies of this early RA population.

Research paper thumbnail of OP0173 How Much of A Barrier Is Excess Weight and Smoking for Achieving Sustained Remission in Early RA? Results from The Canadian Early Arthritis Cohort

Annals of the Rheumatic Diseases, Jun 1, 2016

Background: Fatigue is common in early RA(ERA) and though some patients experience improvement in... more Background: Fatigue is common in early RA(ERA) and though some patients experience improvement in fatigue when disease is well controlled, others experience persistent fatigue associated with work disability, poor QOL, and depression. Objectives: To compare patterns and predictors of improved vs. persistent fatigue in the first year of ERA. Methods: Data were from ERA patients (symptoms <1 year) enrolled in the Canadian Early Arthritis Cohort (CATCH) from 01-2007 to 03-2017. All met ACR1987 or 2010 ACR/EULAR criteria, had active disease, were on DMARDS, and complete fatigue (0-10) data over ! 12 months. Patients were classified at baseline with low (<4) or high (!4) fatigue; high fatigue patients were categorized at 12-months as improved (# !2) or persistent (# <2). Multivariable logistic regression was used to identify predictors of improved vs. persistent fatigue at 12 months in those with high baseline fatigue. Results: The 1002 pts were mostly white (81%), female (71%), with a mean (SD) age of 54 (15); 32% were obese. 70% had high fatigue at baseline; these patients were more obese, had OA/backpain, poor sleep, depression, major stress, and higher disease activity (Table 1). Among those with initial high fatigue, 30% had persistent fatigue at 12 months and was associated with obesity, comorbidities, FM, longer symptom duration, and slightly lower baseline fatigue.

Research paper thumbnail of SAT0055 Treatment Response To Conventional Disease Modifying Anti-Rheumatic Drugs (Dmards) and Biologics in Seropositive and Seronegative Patients with Early Rheumatoid Arthritis: Results from Catch (Canadian Early Arthritis Cohort)

Annals of the Rheumatic Diseases, Jun 1, 2016

NCT01197755). Patients who did not achieve ACR20 at week 12 were given active drug and were consi... more NCT01197755). Patients who did not achieve ACR20 at week 12 were given active drug and were considered escapers. Radiographic progression was assessed by increase in JSN, erosion (ERN) or modified total sharp score (mTSS) after 24 weeks. Only 270 patients had radiographic assessment at both baseline and at 24 weeks. C1M was assessed in fasting serum at baseline (BL). One-way ANOVA was used to assess differences in BL demographics. Associations between BL demographics were investigated by Spearman's correlation. Multiple regression included age group, gender, disease duration, BMI, CRP and BL radiographic status. Non-normalized data was log-transformed. Results: BL demographics of the 3 studies were comparable. 36% of patients were escapers, having BL elevated levels of C1M, CRP and disease activity compared to non-escapers (p=0.03, p<0.0001, p=0.006). 20% of all patients had radiographic progression by JSN, 24% by ERN and 31% by mTSS. BL CRP was significantly elevated in progressors compared to non-progressors (JSN p=0.02, mTSS p=0.005, ERN p=0.005). ERN progressors had a significantly increased level of C1M than non-progressors (p=0.02). JSN only progressors had significant increases in BL radiographic status compared to non-progressors (JSN p=0.003, mTSS p=0.007, ERN p=0.03). At BL there was an association between C1M and radiographic status (JSN rho=0.14, mTSS rho=0.14, ERN rho=0.13,) and disease activity (DAS28 rho=0.44). In multiple regression the effect size β of C1M alone was-0.25, 0.90 and 1.18 for the association with the 24 week change in radiographic progression as determined by JSN, mTSS and ERN, respectively. Only for ERN the effect size reached statistical significance (p=0.0008). The beta value describes the effect of C1M on predicting the radiographic progression. The effect size decreased for JSN when adjusted for CRP (β=-0.68), but for both mTSS and ERN the effect was eliminated. When the other confounders were included the effect size decreased even further for JSN (β=-0.70). Conclusions: In this study we found that BL C1M was associated with structural status and disease activity and that BL C1M was a predictor of radiographic progression (JSN) after 24 weeks when adjusted for confounders. Secondly, escapers had higher level of C1M, CRP and disease activity indication a worse disease stage in escapers at baseline. This study provides supports C1M as an important emerging biomarker of progression in RA. References: [1]

Research paper thumbnail of THU0149 Does Methotrexate Lower Serum Uric Acid Levels? Data from the Catch Cohort

Annals of the Rheumatic Diseases, Jun 1, 2015

Background Methotrexate is the cornerstone DMARD in the treatment of rheumatoid arthritis. The ex... 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

Research paper thumbnail of THU0169 Persistence of Tofacitinib in The Treatment of Rheumatoid Arthritis in Open-Label, Long-Term Extension Studies up To 7 Years

Annals of the Rheumatic Diseases, Jun 1, 2016

Background Tofacitinib is an oral JAK inhibitor for treatment of rheumatoid arthritis (RA). Open-... 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

Research paper thumbnail of OP0178 Body Mass Index is an Independent Risk Factor for not Achieving Sustained Remission in Early Rheumatoid Arthritis: Results from the Catch Observational Study

Annals of the Rheumatic Diseases, Jun 1, 2015

Background Little is known about how lifestyle factors contribute to treatment response in early ... 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.)

Research paper thumbnail of Real-World Tocilizumab Use in Patients with Rheumatoid Arthritis in Canada: 12-Month Results From an Observational, Noninterventional Study

Rheumatology and therapy, Oct 28, 2018

Introduction: This study was conducted to observe patterns of use of the interleukin-6 receptor-a... more Introduction: This study was conducted to observe patterns of use of the interleukin-6 receptor-alpha inhibitor tocilizumab in routine clinical practice in patients with rheumatoid arthritis (RA). Methods: This was a 12-month noninterventional, observational study in adult patients with RA who initiated tocilizumab in routine practice in Canada according to the local product monograph. The primary end point was the proportion of patients receiving tocilizumab at 6 months. Secondary end points were treatment patterns, effectiveness, and safety of tocilizumab over 12 months. Results: Of 200 patients who initiated tocilizumab (91.0% at 8 mg/kg), 67 (33.5%) received tocilizumab monotherapy and 133 (66.5%) received tocilizumab combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Kaplan-Meier analysis estimated that 85% (95% CI 74-92%) of monotherapy and 89% (95% CI 82-93%) of combination therapy patients continued to receive tocilizumab at 6 months (log-rank p = 0.0888). During the observation period, 12 (17.9%) monotherapy and 27 (20.3%) combination therapy patients withdrew from the study. At month 12, 58.5% in the monotherapy group and 59.3% in the combination therapy group achieved Disease Activity Score at 28 joints remission (B 2.6), 25.6% and 24.7% achieved Simplified Disease Activity Index remission (B 3.3), and 18.2% and 22.3% achieved Clinical Disease Activity Index remission (B 2.8), respectively. Rates of serious adverse events and serious infections were found in 29.6/100 patient-years (PY) and 3.1/ 100 PY, respectively, for monotherapy and 19.2/ 100 PY and 4.8/100 PY, respectively, for combination therapy.

Research paper thumbnail of POS1567 OUTCOMES and Predictors of Chronic Immune Checkpoint Inhibitor Induced Inflammatory Arthritis: Data from the Canadian Research Group of Rheumatology in Immuno-Oncology (Canrio) Retrospective Cohort

Annals of the Rheumatic Diseases

BackgroundImmune checkpoint inhibitors (ICI) improve overall survival and progression-free surviv... 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...

Research paper thumbnail of AB1768-HPR SAFETY and Efficacy of Immune Checkpoint Inhibitors in Patients with Rheumatic Autoimmune Disease: Experience from the Canadian Research Group of Rheumatology in Immuno-Oncology (Canrio)

Health Professionals in Rheumatology Abstracts

BackgroundImmune checkpoint inhibitors (ICI) have changed the landscape of treatment for many can... 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...