Tofacitinib Safety and Effectiveness in Canadian Patients with Rheumatoid Arthritis by Cardiovascular Risk Enrichment: Subanalysis of the CANTORAL Study.

INTRODUCTION: ORAL Surveillance, a post-authorisation safety study of patients with rheumatoid arthritis (RA) enriched for cardiovascular (CV) risk, demonstrated increased risk of major adverse CV events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) for tofacitinib versus tumour necrosis factor inhibitors (TNFi). This analysis of a real-world Canadian observational study evaluated tofacitinib safety/effectiveness in patients meeting or not meeting CV risk criteria. METHODS: CANTORAL included patients with moderate-to-severe RA initiating tofacitinib (10/2017-07/2020; N = 504). Interim data (data-cut: 07/2021) were stratified as CV risk-enriched (CV+ ; patients ≥ 50 years with ≥ 1 additional CV risk factor) or not CV risk-enriched (CV-; ≥ 50 years without additional CV risk factors and 18-49 years with/without CV risk factors). Safety and persistence were evaluated to month (M) 36. Effectiveness outcomes to M18 included Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA)/remission (CANTORAL co-primary endpoints) and Disease Activity Score in 28 joints, C-reactive protein (DAS28-4[CRP]) < 3.2/ < 2.6. RESULTS: Overall, 272/232 patients were included in CV+ /CV- cohorts (full analysis set) (435/356 patient-years [safety analysis set]). Incidence rates (events/100 patient-years) in CV+ /CV- cohorts were 138.5/112.5 for treatment-emergent adverse events (AEs); 17.0/5.6 for serious AEs; 1.2/0.3 for deaths; 5.5/1.7 for serious infections; 1.4/1.1 for herpes zoster; 1.6/0.0 for MACE; 2.1/0.3 for malignancies (excluding NMSC); 0.7/0.6 for NMSC; 0.5/0.0 for venous thromboembolic events. Persistence was generally comparable between cohorts. In CV+ /CV- cohorts, at M6, CDAI LDA and remission rates were 51.5%/54.6% and 12.0%/19.6%; DAS28-4(CRP) < 3.2/ < 2.6 rates were 44.0%/39.3% and 31.5%/28.8%, respectively; effectiveness was generally maintained to M18. CONCLUSIONS: In concordance with studies of background risk, AEs were more common in patients with CV risk enrichment, particularly those aged ≥ 65 years. Tofacitinib effectiveness/persistence were generally similar regardless of CV risk enrichment. These findings support individualised treatment benefit-risk assessment, including CV assessment/management, to optimise RA outcomes.

Use of Apremilast to Achieve Psoriatic Arthritis Treatment Goals and Satisfaction at 1 Year in the Canadian Real-World APPRAISE Study.

INTRODUCTION: The APPRAISE study was conducted to better understand the 12-month effectiveness, tolerability, and patient satisfaction with apremilast treatment for patients with psoriatic arthritis (PsA) in real-world settings. METHODS: APPRAISE (NCT03608657), a prospective, multicenter, observational study, enrolled adults with active PsA prescribed apremilast per routine care between July 2018 and March 2020. Patients were followed for 12 months with visits suggested every 4 months. The primary outcome measure was achievement of remission (REM) or low disease activity (LDA), defined as a Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) score ≤ 13. RESULTS: Of the 102 patients who enrolled, 45 (44.1%) discontinued the study by 12 months. Most patients (75.5%) had moderate or high disease activity, and 24.5% were in REM/LDA at baseline based on cDAPSA score. Achievement of cDAPSA REM/LDA was 63.7%, 67.2%, and 53.8% at months 4, 8, and 12, respectively. In those continuing in the study, significant improvements were seen in swollen and tender joint counts, pain visual analog scale, psoriasis body surface area, and complete dactylitis resolution. Enthesitis reduction was also observed. Improvements in treatment satisfaction and patient-reported outcomes, including Health Assessment Questionnaire-Disability Index and the 36-item Short Form physical and mental component scores, were observed over 12 months. The proportion of patients achieving a Patient-Acceptable Symptom State (PASS) increased significantly from baseline at months 4, 8, and 12 (P < 0.001). Apremilast was well tolerated; the most frequent adverse events (AEs) leading to discontinuation were diarrhea (9/102 [8.8%]), nausea (4/102 [3.9%]), and migraine (4/102 [3.9%]). CONCLUSION: In this real-world study conducted in Canadian rheumatology clinics, apremilast demonstrated clinical effectiveness in patients with active PsA, along with patient satisfaction with treatment. Safety findings were consistent with previously reported clinical data. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03608657.

Use of medical cannabis by patients with fibromyalgia in Canada after cannabis legalisation: a cross-sectional study.

OBJECTIVES: Medications have only small to moderate effects on symptoms in fibromyalgia (FM). Cannabinoids, including medical cannabis (MC) may have potential to fill this gap. Since recreational legalisation of cannabis in Canada, patients have easier access and may be self-medicating with cannabis. We have examined the prevalence and characteristics of MC use in FM patients. METHODS: During a two-month period (June-August 2019), consecutive attending rheumatology patients participated in an onsite survey comprising 2 questionnaires: 1) demographic and disease information completed by the rheumatologist, 2) patient anonymous questionnaire of health status, cannabis use (recreational and/or medicinal) and characteristics of use. RESULTS: In a cohort of 1000 rheumatology attendees, 117 (11.7%) were diagnosed with FM. Ever use of MC was reported by 28 (23.9%; 95%CI: 16.5%-32.7%) FM patients compared to 98 (11.1%; 95%CI: 9.1%-13.4%) non-FM patients. Among FM ever users, 17 (61%) patients continued use of MC. FM ever users vs. FM nonusers tended to be younger, 53 vs. 58 years (p=0.072), were more likely unemployed or disabled 39% vs. 17% (p=0.019) and used more medication types (p=0.013) but did not differ in symptom severity parameters. Cigarette smoking and recreational cannabis were more common in ever users. Global symptom relief on a VAS (1-10) was 7.0±2.3. CONCLUSIONS: FM patients have commonly used MC, with more than half continuing use. Reported symptom relief was substantial. Cigarette smoking and recreational cannabis use may play a facilitatory role in MC use in FM. Adjunctive MC may be a treatment consideration for some FM patients.

Safety and therapeutic value of radiosynoviorthesis with yttrium-90: a Canadian single-centre experience.

BACKGROUND: Yttrium-90 (90Y) is approved in several countries as a radiosynoviorthesis agent in the intra-articular treatment of synovitis, however, no such radiopharmaceuticals are approved in Canada. The aim of this Health Canada-approved study was to examine the safety and efficacy of 90Y synovectomy among patients with refractory synovitis. METHODS: We performed a subset analysis of a prospective, phase III, single-arm, pan-Canadian trial. Large and medium-sized joints of adults with refractory inflammatory mono- or oligo-arthritis and minimal cartilage/bone destruction who failed treatment with two intra-articular corticosteroid injections were eligible. Patient follow-up was at 3, 6 and 12 months. Outcome measures included joint tenderness, swelling, effusion, joint function and bone scans. RESULTS: A total of 79 joints were included (90% knees). The underlying diagnosis included SpA (35.2% of patients), RA (26.8%), JIA (8.5%) and other (29.6%). Non-biologic DMARDs were concurrently used in 59.2% of patients and biologic/targeted synthetic DMARDs in 31%. Five adverse events occurred, including one serious radiation burn requiring surgery. All events were non-life-threatening and resolved. Significant improvements in joint tenderness, swelling and effusion were achieved at 3 months (P < 0.001), which were maintained until 12 months. During follow-up, 92.3% of joints did not show radiographic progression. Per the treating physician, clinically important improvement in joint function was observed in 90% of joints. CONCLUSION: Our results confirm the safety of 90Y radiosynoviorthesis in refractory synovitis and provide preliminary evidence supporting its clinical efficacy with sustained benefit at 12 months, suggesting that it is a safe alternative to surgical synovectomy in such cases. This is the first such study in a Canadian cohort.

Changes in Market Share of Biologic and Targeted Synthetic Disease-Modifying Anti-Rheumatic Drugs for Treatment of Rheumatoid Arthritis: Results from the Ontario Best-Practice Research Initiative Database.

OBJECTIVE: For patients with Rheumatoid Arthritis (RA) who do not achieve adequate clinical response with combined conventional synthetic disease-modifying anti-rheumatic drugs (cs- DMARDs), initiation of advanced therapies such as biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) is recommended. Tumour necrosis factor inhibitors (TNFi) are the oldest and most commonly used subgroup of advanced therapies. In the last decade, new non-TNFi advanced therapy options have become available. We described the relative use of TNFi vs. non-TNFi in Ontario-based practices from 2008-2017. METHODS: Adult patients with RA enrolled in the Ontario Best Practices Research Initiative (OBRI) database who started bDMARDs or tsDMARDs anytime during or within 30 days prior to enrollment were included. The proportion of patients treated with TNFi vs. non-TNFi agents between 2008 and 2017 was described for all patients and those initiating their first bDMARD/tsDMARD. All TNFi therapies were included. Non-TNFi included Abatacept, Rituximab, Tocilizumab, and Tofacitinib. RESULTS: A total of 1,057 patients were included, of whom 72.0% were bDMARD/tsDMARD naïve. In 2008, the relative non-TNFi use was 5.4% in all patients while it was 0% in bDMARD/ts- DMARD-naïve patients. In 2017, the proportion of patients using non-TNFi increased to 33.8% among all patients and 33.3% in bDMARD/tsDMARD-naïve patients. CONCLUSION: This descriptive analysis of data from the OBRI cohort reveals that TNFi are still used in the majority of cases; however, there has been an increase in the use of non-TNFi therapies both overall and as first-line advanced therapy. This trend towards non-TNFi therapies as first-line advanced therapy may be partially explained by the shift in guideline recommendations from TNFi as first-line to any of the advanced therapeutics.

An open-label randomized controlled trial of DMARD withdrawal in RA patients achieving therapeutic response with certolizumab pegol combined with DMARDs.

OBJECTIVES: The objective of this trial was to compare effectiveness of certolizumab pegol added to conventional synthetic DMARDs (csDMARDs) in RA patients, followed by continuing vs discontinuing background csDMARDs after treatment response. METHODS: Patients with active RA who had certolizumab pegol added to their existing csDMARD regimen due to inadequate response were eligible. At 3 or 6 months, patients who achieved a change (Δ) in DAS28 of ⩾1.2 were randomized to continue combination therapy (COMBO) or withdraw csDMARD therapy (MONO) (unblinded). The primary outcome was non-inferiority of stopping vs continuing csDMARD(s) in terms of maintaining ΔDAS28 ⩾ 1.2 or achieving DAS28 low disease activity at 18 months (non-inferiority margin: 15 percentile units). RESULTS: A total of 125 patients were enrolled, 88 randomized to COMBO (n = 43) or MONO (n = 45). No significant differences were observed between groups in baseline age, gender, race, RF status or prior biologics (16% vs 11%). Although the rate of ΔDAS28 ⩾ 1.2 and/or DAS28 low disease activity achievement at 18 months was clinically comparable between the two groups (72% vs 69%), non-inferiority assumptions were not met [absolute risk difference (upper limit of 90% CI): 2.6% (19.1%)]. Similar baseline-adjusted improvements were seen in DAS28 (COMBO vs MONO: -2.3 vs -2.1; P = 0.49) and all endpoints were not statistically different including 59% vs 56% achieved DAS28 low disease activity, 69% vs 59% ΔDAS28 ⩾ 1.2, and 41% each remission. CONCLUSION: Among RA patients achieving a therapeutic response on combination therapy with certolizumab pegol and csDMARDs, withdrawing csDMARDs was not non-inferior to maintaining csDMARDs but improvements were sustained in both groups at 18 months.

Toward Defining Primary and Secondary Nonresponse in Rheumatoid Arthritis Patients Treated with Anti-TNF: Results from the BioTRAC and OBRI Registries.

OBJECTIVE: Although most patients with rheumatoid arthritis (RA) respond to anti-tumor necrosis factor (anti-TNF) treatment, some present with initial nonresponse (1ry nonresponse) or lose initial responsiveness (2ry nonresponse). We compared the rate of real-world "nonresponse" to first anti-TNF as reported by treating physicians to the nonresponse rate per accepted definitions and recommended treat-to-target strategies. METHODS: Patients were included from the Biologic Treatment Registry Across Canada (BioTRAC) and Ontario Best Practices Research Initiative (OBRI) registries who were taking their first anti-TNF, with ≥ 1 followup visit. Posthoc reclassification of physician-reported nonresponse was based on prior achievement of 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), Clinical Disease Activity Index (CDAI) LDA, or good/moderate European League Against Rheumatism (EULAR) response, and actual time of physician-reported nonresponse. RESULTS: Among 736 BioTRAC and 640 OBRI patients, 13.7% and 18%, respectively, discontinued their anti-TNF because of physician-reported nonresponse. Based on reclassification using disease activity, 65.6% (BioTRAC) and 87.2% (OBRI) of 1ry nonresponders did not achieve DAS28-ESR LDA, 65.6%/90.7% CDAI LDA, and 46.9%/61.5% good/moderate EULAR response. Among 2ry nonresponders, 50.7%/47.8% did not achieve DAS28-ESR LDA, 37.7%/52.9% CDAI LDA, and 15.9%/19.6% good/moderate EULAR response before treatment discontinuation. Regarding actual time of nonresponse, 18.8% of BioTRAC and 60.8% of OBRI 1ry nonresponders discontinued at ≤ 6 months. In both registries, a high proportion of 2ry nonresponders discontinued their anti-TNF after 12 months (87.0% BioTRAC, 60.9% OBRI). CONCLUSION: Physician-reported 1ry nonresponse was more correlated with non-achievement of DAS28-ESR LDA or CDAI LDA, whereas 2ry nonresponse with actual time of discontinuation. Further work is needed to confirm the importance of response and type of response to the initial anti-TNF in identifying patients most likely to benefit from a second biologic agent treatment.

Impact of residential area on the management of rheumatoid arthritis patients initiating their first biologic DMARD: Results from the Ontario Best Practices Research Initiative (OBRI).

Access to care and management of Rheumatoid Arthritis (RA) patients may differ based on residential area. We described differences in the profile of patients initiating their first biologic disease modifying antirheumatic drug (bDMARD) based on their residential area type.Cross-sectional analysis of 793 adult RA patients in the longitudinal Ontario Best Practices Research Initiative (OBRI) registry initiating their first bDMARD <30 days prior to or anytime post-enrolment. Patient residential and clinic areas (rural vs. urban) were classified using 2 methods: postal codes and Statistics Canada population centres. Sociodemographics, disease characteristics, and RA medications (tumor necrosis factor inhibitor [TNFi] vs. non-TNFi, concurrent use of conventional synthetic DMARDs [csDMARDs], and intravenous [IV] vs. subcutaneous [SC] bDMARD) at initiation of first bDMARD were contrasted between residential area types.Other than marital status, first language, and race (higher proportion of married, English speaking, Caucasian patients in rural areas), no significant differences were observed in the demographic and disease characteristics of patients living in rural and urban areas. In multivariate analysis, there was no association between residential area type and type of bDMARD use, concurrent csDMARD(s) use or route of bDMARD. However, patients living farther from their treating clinic were significantly less likely to initiate IV bDMARD. Female rheumatologist and rural clinic location were independently associated with lower odds of IV bDMARD use.The use of SC vs. IV bDMARD was associated with being seen in a clinic located in a rural area, being treated by a female rheumatologist, and living farther from treating clinic. These results suggest possible prescription bias in bDMARD selection and/or patient preferences due to convenience.

Autologous endometrial cell co-culture improves human embryo development to high-quality blastocysts: a randomized controlled trial.

RESEARCH QUESTION: Does autologous endometrial cell co-culture (AECC) improve the number of good-quality blastocysts obtained by IVF/intracytoplasmic sperm injection (ICSI), compared with conventional embryo culture medium in a broad group of patients referred to assisted reproductive technology (ART)? DESIGN: This interventional, randomized, double-blind study took place at Clinique Ovo from March 2013 to October 2015 and included 207 healthy patients undergoing an IVF or ICSI protocol, of which 71 were excluded before randomization. On the previous cycle, all participants underwent an endometrial biopsy at D5 to D7 post-ovulation, following which the endometrial cells were prepared for AECC. RESULTS: The data demonstrated that AECC significantly increased the incidence of good-quality blastocysts compared with culture in conventional media (42.6% vs 28.4%, P < 0.001). No significant differences were found in pregnancy and live birth rates. CONCLUSION: This study demonstrated the benefits of AECC on blastocyst quality compared with conventional embryo culture medium, in a broader category of patients referred to ART as opposed to other studies that concentrated on specific causes of infertility only. However, limitations of the study design should be taken into consideration; the analysis was performed using embryos rather than patients and a follow-up of children born following the treatments could not be conducted.

Measuring herpes zoster disease burden in São Paulo, Brazil: a clinico-epidemiological single-center study

OBJECTIVES: Herpes zoster is characterized by acute neuritis and post-herpetic neuralgia. Currently, data concerning the zoster-associated impact on quality of life and healthcare resource utilization in Brazil are scarce. This study measured the zoster-associated burden in a Brazilian population. METHODS: This was a prospective, observational, single-cohort study conducted in a primary hospital's emergency room in São Paulo, Brazil. Patients enrolled at various timepoints during a zoster episode were followed over 180 days. The Zoster Brief Pain Inventory and the Initial Zoster Impact Questionnaire assessed zoster-associated pain. The EuroQoL assessed the impact of herpes zoster and/or zoster-associated pain on quality of life. Healthcare resource utilization was assessed by patient-reported questionnaires. RESULTS: One-hundred forty-six zoster patients were enrolled [mean (SD) age of 69.9 (10.9) years]. Mean (SD) worst pain scores decreased from 5.3 (3.5) at baseline to 1.9 (3.0) 180 days following rash onset. Mean (SD) EuroQoL scores significantly decreased from 0.9 (0.2) before rash appearance to 0.7 (0.2) after rash onset (p<0.001), followed by gradual improvements in quality of life over 180 days, with pre-herpes zoster quality of life achieved at the end of the observation period. The majority of patients purchased prescription medications (89.7%) and required doctor's office visits (65.8%) for zoster episodes. CONCLUSIONS: Herpes zoster is associated with a significant disease burden, including zoster-associated pain, impaired quality of life and increased healthcare resource utilization in Brazil. These results support the implementation of early intervention and prevention programs such as vaccinations to reduce the herpes zoster-associated disease burden in Brazil.

Measuring the burden of herpes zoster disease in Costa Rica

AbstractBackground: Herpes zoster is a distressing illness that significantly reduces patients' quality of life. However, Costa Rican data regarding the clinical burden of herpes zoster and associated health care resource utilization is limited. This study aimed to assess the zoster-associated burden evaluating pain, impact on quality of life and health care resource utilization in a Costa Rican sample.Methods:Herpes zoster patients recruited in Costa Rica at a private geriatric practice were enrolled at various time points during a zoster episode and were actively followed over 6 months. Outcomes including zoster-associated pain, quality of life and health care resource utilization were assessed via patient self-reported questionnaires.Results: 50 zoster patients were included [68.0% female, mean (SD) age = 69.5 (10.8) years]. Zoster-associated pain decreased over time while quality of life improved though without full base recovery. The highest health care resource utilization included doctor's office (98.0%), emergency room (60.0%) and specialists (60.0%) visits. Sixteen (32.0%) patients were hospitalized [mean (SD)= 4.3 (4.1) days].Conclusion: Similar to other Latin American countries, high herpes zoster burden was observed in a private geriatric practice in Costa Rica, supporting the need for early intervention and preventive strategies, one of such could be the implementation of a HZ vaccination program.

ResumenJustificación: El herpes zoster es una enfermedad estresante que reduce significativamente la calidad de vida de los pacientes. Sin embargo, datos relativos a la carga clínica de herpes zoster y la utilización de recursos de salud son limitados en Costa Rica. El objetivo de este estudio fue evaluar la carga asociada al herpes zoster evaluando dolor, impacto sobre la calidad de vida y utilización de recursos de salud en una muestra costarricense.Métodos:Pacientes con herpes zoster fueron reclutados en una práctica geriátrica privada en diferentes etapas de un episodio de zoster y fueron activamente seguidos durante 6 meses. Se evaluaron los resultados en el paciente, incluyendo el dolor asociado a zoster, calidad de vida y utilización de recursos de salud mediante cuestionarios autoadministrados.Resultados: Se incluyeron 50 pacientes con herpes zoster [68,0% mujeres, media de edad (SD) = 69.5 (10.8) años]. El dolor asociado a zoster disminuyó con el tiempo mientras que calidad de vida mejoró, aunque sin plena recuperación comparado con la calidad de vida inicial. La utilización de recursos de salud más alta fue visitas al consultorio (98.0%), visitas a sala de urgencias (60.0%) y visitas a especialistas (60.0%). Dieciséis pacientes (32.0%) fueron hospitalizados [media (SD) = 4.3 (4.1) días].Conclusión: Similar a otros países de América Latina, se observó una alta carga de enfermedad debido a herpes zoster en una práctica privada geriátrica en Costa Rica, lo cual respalda la necesidad de la intervención temprana y uso de estrategias preventivas, una de las cuales podría ser la implementación de un programa de vacunación a herpes zoster.

Predictors of patient decision to discontinue anti-rheumatic medication in patients with rheumatoid arthritis: results from the Ontario best practices research initiative.

Despite the availability of treatment guidelines and effective treatments, real-world effectiveness remains suboptimal partly due to poor patient medication adherence. We evaluated a comprehensive set of sociodemographic, health insurance, and disease-related factors for association with patient decision to discontinue anti-rheumatic medications (ARMs) in a large observational RA cohort in Ontario, Canada. Patients from the Ontario Best Practices Research Initiative registry were included. The following predictors of ARM discontinuation were evaluated with cox-regression: patient age, gender, education, income, smoking, health insurance type/coverage, RA duration, erosion presence, RF positivity, DAS28-ESR, physician global, HAQ-DI, comorbidity number, ARM types, and physician characteristics (gender, academic position, urban vs. rural, distance from patient's residence). Patients (1762) were included with a mean (SD) age of 57.4 years (13.0). Approximately 80% were female, 29% had early (≤ 1 year) RA, and 70% were RF-positive. Mean (SD) baseline DAS28-ESR and HAQ-DI were 4.5 (1.5) and 1.2 (0.76), respectively. In multivariate analysis, married status (HR [95%CI] 0.73 [0.56-0.96]), RF positivity (0.73 [0.56-0.96]), and higher comorbidity number (0.92 [0.85-0.99]) were significant predictors of ARMs continuation while higher physician global (1.10 [1.04-1.15]), NSAID use (1.75 [1.29-2.38]), and number of ARMs (1.23 [1.07-1.40]) were associated with ARMs discontinuation. In a subset analysis assessing conventional or biologic DMARD discontinuation, higher HAQ-DI and biologic use over time were associated with lower hazard for discontinuation. Several sociodemographic, disease, and treatment parameters were identified as independent predictors of patient discontinuation of ARMs. These results should be considered when developing patient adherence support programs and in the choice of treatment regimens.

Navigating the clinical trial pathway: Conception, design, execution, and results dissemination.

Dr Sampalis is founder, Chief Executive Officer, and Chief Scientific Officer of JSS Medical Research Inc, founded in 1997. He is a tenured professor of Surgery and Epidemiology & Biostatistics of McGill University, the University of Montreal and University of Laval. Recognized as a leading clinical epidemiologist and one of the top trauma researchers in Canada, he possesses extensive expertise in health services research, clinical trials, and offers services as a Research and Epidemiological Consultant for numerous pharmaceutical companies, hospitals and government organizations and agencies. Mrs. Watson holds a M.Sc. in Pharmacology from Dalhousie University, and a B.Sc. from the University of Western Ontario. Her experience extends to all facets of the CRO business, and multiple therapeutic areas. She co-founded, in 1992, Integrated Research Inc, a full-service contract research organization, and served as its President and Chief Executive Officer, until merging with JSS Medical Research Inc in 2014. Mrs. Watson currently holds the position of Chief Business Officer, and is head of the business development team. Mrs. Boukas has been working with the JSS Medical Research team since its inception in the 1990s. She holds a B.A. in Psychology from McGill University with training in Epidemiology and Biostatistics, and is certified by the Society of Clinical Research Associates (SOCRA) as a Certified Clinical Research Professional (CCRP). She has over 25 years' of experience in medical research management. Currently Chief Operations Officer, Mrs. Boukas has been essential in structuring and implementing programs at JSS Medical Research Inc to facilitate project management, site recruitment, data capture and study tracking. Mrs. Boukas holds a B.A. from McGill University, a Certificate in Technical Communications from Concordia University and has received compliance training from SNC Lavalin Pharma (SLP) and SOCRA. She has over twenty-five years' experience in research. Joining JSS Medical Research Inc in 1998, she currently holds the position of Executive Director of Quality Assurance (QA) where she developed and maintains the QA Program since 2004. The QA Program supports clinical studies conducted in Canada, Latin America, India and Europe. Mrs. Harvey holds a B.Sc. in Biochemistry from the Université du Québec à Montréal and a M.Sc. in Biology from McGill University. With 20 years' experience in the pharmaceutical industry, she has held positions in both Commercial and Medical departments. Mrs. Harvey currently holds the position of Director, Clinical Operations at JSS Medical Research Inc, functionally and operationally overseeing a team of project and data managers in the development and implementation of clinical studies. Dr Machado obtained his medical degree from the University of Pune, India. He has over 20 years' experience in multinational pharmaceutical, CRO, Bioequivalence & Phase I and Site Management Organizations, working in several therapeutic areas and phase of studies. As a founder of Venn Life Sciences, Dr Machado served as Chief Operating Officer, until joining JSS Medical Research Inc in 2011, where he is currently Vice-President, Global Operations & Integration. In addition to overseeing global operations, he is responsible for global expansion and integration of JSS Medical Research Inc through acquisitions and mergers. Mr. Bordeleau holds a B.Sc. in Biochemistry from the University of Guelph and an MBA from HEC Montreal. He has over 20 years' experience in the pharmaceutical industry, including laboratory and IT research, healthcare marketing support, and IT team management. As Global Director of information Technology at JSS Medical Research Inc, Mr. Bordeleau leads a team of programmers as well as network, database and system administrators who specialize in developing, maintaining, and most importantly, improving, key software, clinical systems, infrastructure, and business processes. Dr Rampakakis received his Ph.D. from the Department of Biochemistry from McGill University, and obtained post-doctoral training, also at McGill, in Pharmacoepidemiology. With over 15 years' experience in scientific research, he has contributed in the conception, design, analysis and interpretation of several large scale, national and international, registration and observational studies. He currently holds the position of Vice President of Scientific Affairs at JSS Medical Research Inc, overseeing a team of biostatisticians, epidemiologists, physicians, medical writers, and health economists.

Survey of herbal cannabis (marijuana) use in rheumatology clinic attenders with a rheumatologist confirmed diagnosis.

Cannabinoids may hold potential for the management of rheumatic pain. Arthritis, often self-reported, is commonly cited as the reason for the use of medicinal herbal cannabis (marijuana). We have examined the prevalence of marijuana use among 1000 consecutive rheumatology patients with a rheumatologist-confirmed diagnosis and compared in an exploratory manner the clinical characteristics of medicinal users and nonusers. Current marijuana use, medicinal or recreational, was reported by 38 patients (3.8%; 95% CI: 2.8-5.2). Ever use of marijuana for medical purposes was reported by 4.3% (95% CI: 3.2-5.7), with 28 (2.8%; 95% CI: 1.9-4.0) reporting current medicinal use. Current medicinal users had a spectrum of rheumatic conditions, with over half diagnosed with osteoarthritis. Medicinal users were younger, more likely unemployed or disabled, and reported poorer global health. Pain report and opioid use was greater for users, but they had similar physician global assessment of disease status compared with nonusers. Medicinal users were more likely previous recreational users, with approximately 40% reporting concurrent recreational use. Therefore, less than 3% of rheumatology patients reported current use of medicinal marijuana. This low rate of use in patients with a rheumatologist-confirmed diagnosis is in stark contrast to the high rates of severe arthritis frequently reported by medicinal marijuana users, especially in Canada. Familiarity with marijuana as a recreational product may explain use for some as disease status was similar for both groups.

Dolor, calidad de vida relacionada con la salud y utilización de servicios médicos asociados al herpes zoster en Argentina / Herpes zoster-associated pain, health-related quality of life, and healthcare utilization in Argentina

El herpes zoster (HZ) es causado por reactivación del virus varicela-zoster latente. Se caracteriza por exantema vesicular unilateral, neuri-tis aguda y neuralgia posherpética. Aún hay escasos datos sobre el do-lor asociado al HZ (DAZ), su repercusión en la calidad de vida (CdV) y la utilización de recursos sanitarios (URS) asociada en Argentina. En este estudio prospectivo, observacio-nal, de una cohorte, realizado en 3 centros argenti-nos se valuó la carga de morbilidad asociada al HZ en Argentina en contextos clínicos reales. Los pa-cientes fueron enrolados en diversos momentos du-rante un episodio herpético, y seguidos activamen-te los días 14, 21, 30, 60, 90, 120, 150 y 180. Hubo 96 enrolados(edad 70±10,7 años; tiempo desde el inicio del exantema 16±16,9 días[media±DE]). El puntaje del peor dolor (media±DE) disminuyó de 5,5±3,1 en el enrolamiento a 0,2±0,7 a los 180 días de seguimiento. El puntaje del cuestionario de cali-dad de vida EQ-5D (media±DE) disminuyó significa-tivamente de 0,8±0,1 antes del inicio del exantema a 0,6±0,2 tras su inicio (P<0,001), con mejoría gra-dual de la CdV durante 180 días (0,9±0,1), hasta un puntaje similar al previo al inicio del exantema. La URS más frecuente fueron visitas al consultorio mé-dico (96,9%). La gran mayoría de pacientes compró medicamentos recetados (95,8%) y de venta sin receta (83,3%) para los episodios herpéticos. El DAZ estuvo asociado a gran carga de morbili-dad, deterioro de CdV, aumento de URS y costos asociados en Argenti-na. Esto subraya la importancia de estrategias de intervención precoz o prevención para disminuir la carga de morbilidad asociada al HZ

Herpes zoster (HZ) is caused by re-activation of latent varicella zoster virus and is characterized by unilateral, vesicular cutaneous eruptions, acute neuritis, and post-herpetic neuralgia. To date, data on HZ associated pain (ZAP) and its impact on quality of life (QoL) and associated healthcare resource utilization use (HCRU) in Argentina is scarce. This study assessed the burden of illness associated with HZ in Argentina in a real-life clinical setting. This was a prospective, observational, single-cohort study conducted in 3 sites across Argentina. Patients were enrolled at various time points during the course of a zoster episode and were actively followed on days 14, 21, 30, 60, 90, 120, 150, and 180. There were 96 HZ patients enrolled with a mean±SD age and time since rash onset of 70±10. 7 years and 16±16. 9 days, respectively. Mean±SD worst pain score decreased from 5. 5±3. 1 at enrollment to 0. 2±0.7 at 180 days of follow-up. The mean±SD EQ-5D score significantly decreased from 0. 8±0. 1 before rash onset to 0. 6±0. 2 after rash onset (P <0.001) followed by gradual improvement in QoL over 180 days (0. 9±0.) reaching a similar score to that prior to rash onset. The most common HCRU was visits to the doctor's office with 96.9%. The vast majority of patients purchased prescription medications (95.8%) and over-the-counter medications (83.3%) for HZ episodes. ZAP was found to be associated with severe burden of illness, impaired QoL, increased HCRU, and associated cost in Argentina; highlighting the importance of early intervention or prevention strategies to reduce HZ-associated disease burden

Biologic Treatment Registry Across Canada (BioTRAC): a multicentre, prospective, observational study of patients treated with infliximab for ankylosing spondylitis.

OBJECTIVES: To describe the profile of patients with ankylosing spondylitis (AS) treated with infliximab in Canadian routine care and to assess the effectiveness and safety of infliximab in real world. SETTING: 46 primary care rheumatology practices across Canada. PARTICIPANTS: 303 biological-naïve patients with AS or patients previously treated with a biological for <6 months and who were eligible for infliximab treatment as per routine care within the Biologic Treatment Registry Across Canada (BioTRAC). INTERVENTION: Not applicable (non-interventional study). PRIMARY AND SECONDARY OUTCOMES: Effectiveness was assessed with changes in disease parameters (AS Disease Activity Score (ASDAS), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Health Assessment Questionnaire Disease Index (HAQ-DI), physician global assessment of disease activity (MDGA), patient global disease activity (PtGA), back pain, C-reactive protein, erythrocyte sedimentation rate (ESR), morning stiffness). Safety was assessed with the incidence of adverse events (AEs). RESULTS: Of the 303 patients included, 44.6% were enrolled in 2005-2007 and 55.4% in 2008-2013. Patients enrolled in 2005-2007 had significantly higher MDGA and ESR at baseline while all other disease parameters examined were numerically higher with the exception of PtGA. Treatment with infliximab significantly (p<0.001) improved all disease parameters over time in both groups. At 6 months, 56% and 31% of patients achieved clinically important (change≥1.1) and major (change≥2.0) improvement in ASDAS, respectively; at 48 months, these proportions increased to 75% and 50%, respectively. Among patients unemployed due to disability at baseline, 12.1% returned to work (mean Kaplan-Meier (KM)-based time=38.8 months). The estimated retention rate at 12 and 24 months was 78.3% and 60.1%, respectively. The profile and incidence of AEs were comparable to data previously reported for tumour necrosis factor-α inhibitors. CONCLUSIONS: Characteristics of patients with AS at infliximab initiation changed over time towards lower disease activity and shorter disease duration. Infliximab treatment significantly reduced disease activity independent of treatment initiation year, although patients enrolled in recent years achieved lower disease activity over 48 months. TRIAL REGISTRATION NUMBER: NCT00741793.

Disability in Fibromyalgia Associates with Symptom Severity and Occupation Characteristics.

OBJECTIVE: It is intuitive that disability caused by illness should be reflected in illness severity. Because disability rates for fibromyalgia (FM) are high in the developed world, we have examined disease and work characteristics for patients with FM who were working, unemployed, or receiving disability payments for disability as a result of FM. METHODS: Of the 248 participants in a tertiary care cohort study of patients with FM, 90 were employed, 81 were not employed and not receiving disability payments, and 77 were not working and currently receiving disability payments awarded for disability caused by FM. Demographic, occupation, and disease characteristics were compared among the groups. RESULTS: The prevalence of disability caused by FM was 30.8%. There were no demographic differences among the working, unemployed, or disabled patients. With the exception of measures for anxiety and depression, all measurements for disease severity differed significantly among the groups, with greater severity reported for the disabled group, which used more medications and participated less in physical activity. Disabled patients were more likely previously employed in manual professions or the service industry, whereas employed patients were more commonly working in non-manual jobs that included clerical, managerial, or professional occupations (p = 0.005). CONCLUSION: The one-third rate of disability for this Canadian cohort of patients with FM is in line with other reports from the western world. Associations of disability compensation were observed for subjective report of symptom severity, increased use of medications, and previous employment in more physically demanding jobs.

Real-life assessment of the validity of patient global impression of change in fibromyalgia.

OBJECTIVES: Patient Global Rating of Change (GRC) scales are commonly used in routine clinical care given their ease of use, availability and short completion time. This analysis aimed at assessing the validity of Patient Global Impression of Change (PGIC), a GRC scale commonly used in fibromyalgia, in a Canadian real-life setting. METHODS: 167 fibromyalgia patients with available PGIC data were recruited in 2005-2013 from a Canadian tertiary-care multidisciplinary clinic. In addition to PGIC, disease severity was assessed with: pain visual analogue scale (VAS); Patient Global Assessment (PGA); Fibromyalgia Impact Questionnaire (FIQ); Health Assessment Questionnaire (HAQ); McGill Pain Questionnaire; body map. Multivariate linear regression assessed the PGIC relationship with disease parameter improvement while adjusting for follow-up duration and baseline parameter levels. The Spearman's rank coefficient assessed parameter correlation. RESULTS: Higher PGIC scores were significantly (p<0.001) associated with greater improvement in pain, PGA, FIQ, HAQ and the body map. A statistically significant moderate positive correlation was observed between PGIC and FIQ improvement (r=0.423; p<0.001); correlation with all remaining disease severity measures was weak. Regression analysis confirmed a significant (p<0.001) positive association between improvement in all disease severity measures and PGIC. Baseline disease severity and follow-up duration were identified as significant independent predictors of PGIC rating. CONCLUSIONS: Despite that only a weak correlation was identified between PGIC and standard fibromyalgia outcomes improvement, in the absence of objective outcomes, PGIC remains a clinically relevant tool to assess perceived impact of disease management. However, our analysis suggests that outcome measures data should not be considered in isolation but, within the global clinical context.

Use of corticosteroids in patients with rheumatoid arthritis treated with infliximab: treatment implications based on a real-world Canadian population.

OBJECTIVE: To describe the rate of concomitant oral corticosteroid use at antitumour necrosis factor (TNF) initiation and at disease remission, and to assess its effect on incidence of infection and sustainability of remission among patients with rheumatoid arthritis (RA) treated with infliximab in Canadian routine care. METHODS: Biological naïve patients with RA followed in the Biologic Treatment Registry Across Canada (BioTRAC) were included. The time-dependent association between corticosteroid dose (no use, ≤5 mg/day, >5 mg/day) and the incidence of first infection, while considering possible confounders, remission sustainability and the incidence of subsequent infections were assessed with Cox regression. RESULTS: 838 patients were included; mean (SD) baseline age and disease duration were 55.6 (13.5) and 10.5 (9.8) years, respectively. After a mean (SD) of 51.3 (43.6) months, the total incidence of adverse events (AEs) and infections were 110.2 and 19.6 per 100 person-years (PY), respectively. In multivariate analysis, the HR (95% CI) for acquiring an infection was 2.48 (1.24 to 4.98) with >5 mg/day of corticosteroids versus no corticosteroids. Similarly, ≤5 mg/day of corticosteroids was associated with increased hazard for infection (2.12 (0.97 to 4.66)). Despite DAS28 (disease activity score 28) or Clinical Disease Activity Index (CDAI) remission, corticosteroids were continued in 16.4% and 16.7% of cases, respectively. Continued corticosteroid treatment was not associated with sustainability of remission (HRDAS28 (95% CI) 1.40 (0.95 to 2.06); HRCDAI 1.19 (0.75 to 1.88)), however, it had a significant impact on development of infection (HRDAS28 (95% CI) 1.78 (1.00 to 3.19); HRCDAI 2.38 (1.14 to 4.99)). CONCLUSIONS: Oral corticosteroid treatment was associated with increased risk of development of infection without impacting sustainability of remission. These results support the notion that corticosteroids should be used concomitantly with anti-TNF for the shortest period possible to achieve remission, and then tapered. TRIAL REGISTRATION NUMBER: NCT00741793.

Predicting depression and quality of life among long-term head and neck cancer survivors.

OBJECTIVE: The aim of this study is to identify clinical factors that are predictive of depression and quality of life (QOL) among long-term survivors of head and neck squamous cell carcinoma and to develop predictive scores using these factors. STUDY DESIGN: Cohort study SETTING: Tertiary referral center. SUBJECTS AND METHODS: A total of 209 posttreatment (median follow-up, 38.7 months) head and neck cancer patients were prospectively evaluated using the Hospital Anxiety Depression Scale (HADS), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30, and the EORTC Quality of Life Questionnaire Head and Neck 35, and pretreatment patient-related, tumor-related, and treatment-related predictors were identified using chart review. Bivariate (χ(2) and t test) and multivariate (linear regression) analyses were used to construct predictive models. RESULTS: Significant pretreatment predictors of depression were identified on multivariate analysis as smoking at diagnosis, >14 alcoholic drinks per week, T3 or T4 status, and >3 medications (P < .001). Two or more of these factors yielded an 82.3% sensitivity in detecting significant depressive symptoms (defined as a HADS cutoff score of 5). Significant predictors of fatigue, global health/QOL, social contact, speech, pain, swallowing, and xerostomia were also identified. CONCLUSION: Pretreatment predictors of long-term depression and QOL have been defined using multivariate models, and an easily applicable predictive score of long-term depression is proposed. Potential eventual clinical applications include prophylactic intervention in at-risk patients.