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ObjectiveTofacitinib (TOF) is an oral, small-molecule drug used for rheumatoid arthritis (RA) treatment and is one of several alternative treatments to tumor necrosis factor inhibitors (TNFi). We evaluated physician- and patient-reported effectiveness of TNFi compared to TOF, using real-world data from the Ontario Best Practices Research Initiative (OBRI).MethodsPatients enrolled in the OBRI initiating TOF or TNFi between 2014 and 2019 were included. Patients were required to have physician- and patient-reported effectiveness outcome data, including Clinical Disease Activity Index (CDAI) and RA Disease Activity Index (RADAI), available at treatment initiation and 6 (± 2) months later. To deal with confounding by indication, we estimated propensity scores (PS) for covariates.ResultsFour hundred nineteen patients were included. Of those, 226 initiated a TNFi and 193 TOF, and had a mean (SD) disease duration of 8.0 (8.7) and 12.6 (9.6) years, respectively. In addition, the TNFi group was less likely to have prior biologic use (21.7%) compared to the TOF group (67.9%). The proportion of patients in CDAI low disease activity (LDA)/remission (REM) at 6 months was 36.7% and 33.2% in the TNFi and TOF groups, respectively. The generalized linear mixed models adjusting for PS quantile showed that there was no significant difference in CDAI LDA/REM (odds ratio [OR] 0.85, 95% CI 0.51–1.43) and RADAI coefficient (OR 0.48, 95% CI –0.18 to 1.14) between the 2 groups (ref: TOF).ConclusionIn patients with RA, physician- and patient-reported effectiveness are similar in the TNFi and TOF groups 6 months after treatment.

ObjectiveTo compare clinical characteristics and treatment of patients with rheumatoid arthritis (RA) across 4 Canadian cohorts.MethodsThe 4 longitudinal cohorts included the following: the Canadian Early Arthritis Cohort (CATCH; n = 2878), Ontario Best Practices Research Initiative (OBRI; n = 3734), RHUMADATA (Quebec, n = 2890), and the Rheum4U Precision Health Registry (Calgary, Alberta, n = 709). Data were from cohort inception (range 1998–2016) to 2020. Clinical characteristics and drug treatments were summarized descriptively.ResultsIn total, 10,211 patients with RA were included. The percentage of patients who entered the cohort with early RA (2 yrs of disease at enrollment) ranged from 29% (Rheum4U) to 100% (CATCH). Mean age (55 yrs), sex (74% female), and seropositivity (69%) were similar between cohorts. At the time of initial disease-modifying antirheumatic drug (DMARD) use, median Disease Activity Score in 28 joints (DAS28) varied, ranging from 2.99 (Rheum4U) to 5.19 (CATCH), but were more similar at the time of the first DMARD switch (range 3.57–5.03), first biologic (bDMARD) or targeted synthetic DMARD (tsDMARD) use (range 4.01–4.67), and second bDMARD or tsDMARD (range 3.71–4.39). The initial DMARD was most commonly methotrexate, either in monotherapy (32%, range 18–40%) or dual therapy (34%, range 29–42%). The first DMARD switch was to another DMARD monotherapy in 20% (range 10–32%), dual therapy in 49% (range 39–56%), and bDMARD or tsDMARD in 24% (range 15–28%). The first bDMARD was an anti–tumor necrosis factor in 79% (range 78–82%).ConclusionCanadian RA cohorts demonstrate some heterogeneity in treatment, which could reflect differences in inclusion criteria, calendar year, or regional differences. This project is a first step toward conducting harmonized analyses across Canadian RA cohorts.

ObjectiveTo provide the initial installment of a living guideline that will provide up-to-date guidance on the pharmacological management of patients with rheumatoid arthritis (RA) in Canada.MethodsThe Canadian Rheumatology Association (CRA) formed a multidisciplinary panel composed of rheumatologists, researchers, methodologists, and patients. In this first installment of our living guideline, the panel developed a recommendation for the tapering of biologic and targeted synthetic disease-modifying antirheumatic drug (b/ts DMARD) therapy in patients in sustained remission using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, including a health equity framework developed for the Canadian RA population. The recommendation was adapted from a living guideline of the Australia & New Zealand Musculoskeletal Clinical Trials Network.ResultsIn people with RA who are in sustained low disease activity or remission for at least 6 months, we suggest offering stepwise reduction in the dose of b/tsDMARD without discontinuation, in the context of a shared decision, provided patients are able to rapidly access rheumatology care and reestablish their medications if needed. In patients where rapid access to care or reestablishing access to medications is challenging, we conditionally recommend against tapering. A patient decision aid was developed to complement the recommendation.ConclusionThis living guideline will provide contemporary RA management recommendations for Canadian practice. New recommendations will be added over time and updated, with the latest recommendation, evidence summaries, and Evidence to Decision summaries available through the CRA website (www.rheum.ca).

Objective.Prior studies have suggested that concurrent conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy enhances the efficacy of biologic DMARD (bDMARD). Here, we assessed the effect of concomitant csDMARD use and methotrexate (MTX) route of administration on time to bDMARD discontinuation in a large Canadian (Ontario), observational, rheumatoid arthritis (RA) cohort.Methods.Patients from the Ontario Best Practices Research Initiative (OBRI) who initiated bDMARD therapy and had ≥ 1 followup assessment were included. The effect of concomitant csDMARD use (primary analysis) and MTX route of administration (secondary analysis) on bDMARD discontinuation owing to (1) any reason, (2) ineffectiveness, (3) adverse events (AE), and (4) both (2) and (3), were assessed with multivariate Cox regression.Results.Among the 814 patients included, 153 (18.8%) received bDMARD monotherapy and 661 (81.2%) combination csDMARD/bDMARD therapy. Over a mean followup of 1.9 years, bDMARD were discontinued in 38.7% of patients. In multivariate analysis, there was a nonsignificant trend toward lower discontinuation for the csDMARD/bDMARD group compared to bDMARD monotherapy for any reason (HR 0.76, 95% CI 0.55–1.05) and owing to ineffectiveness/AE (HR 0.73, 95% CI 0.50–1.06). Further, patients taking combination therapy had significantly lower risk of bDMARD discontinuation due to AE (HR 0.43, 95% CI 0.24–0.76). In the secondary analysis, no statistical association between MTX dose or route of administration and bDMARD durability was observed.Conclusion.Concomitant csDMARD use was associated with a significantly lower hazard for bDMARD discontinuation due to AE among patients with RA followed in routine clinical practice in Ontario, Canada. Neither MTX route of administration nor dose were significant predictors of bDMARD durability.

Objective.We evaluated the influence of triage assessments by extended role practitioners (ERP) on improving timeliness of rheumatology consultations for patients with suspected inflammatory arthritis (IA) or systemic autoimmune rheumatic diseases (SARD).Methods.Rheumatologists reviewed primary care providers’ referrals and identified patients with inadequate referral information, so that a decision about priority could not be made. Patients were assessed by an ERP to identify those with IA/SARD requiring an expedited rheumatologist consult. The time from referral to the first consultation was determined comparing patients who were expedited to those who were not, and to similar patients in a usual care control group identified through retrospective chart review.Results.Seven rheumatologists from 5 communities participated in the study. Among 177 patients who received an ERP triage assessment, 75 patients were expedited and 102 were not. Expedited patients had a significantly shorter median (interquartile range) wait time to rheumatologist consult: 37.0 (24.5–55.5) days compared to non-expedited patients [105 (71.0–135.0) days] and controls [58.0 (24.0–104.0) days]. Accuracy comparing the ERP identification of IA/SARD to that of the rheumatologists was fair (κ 0.39, 95% CI 0.25–0.53).Conclusion.Patients triaged and expedited by ERP experienced shorter wait times compared to usual care; however, some patients with IA/SARD were missed and waited longer. Our findings suggest that ERP working in a triage role can improve access to care for those patients correctly identified with IA/SARD. Further research needs to identify an ongoing ERP educational process to ensure the success of the model.

Objective.We sought to determine if initial high disease activity or changes in disease activity contribute to persistent depression in early rheumatoid arthritis (ERA). We also determined if disease activity and depression is modified by sex.Methods.Depression was ascertained by self-report among patients enrolled in the Ontario Best Practices Research Initiative. The association between baseline disease activity, measured by the Clinical Disease Activity Index (CDAI), and persistent depression was evaluated with multivariate regression models, and effect modification by sex was tested. A general estimating equation assessed the association between change in CDAI over time and risk of depression.Results.The sample of 469 ERA subjects was predominantly female (73%). At baseline, the prevalence of depression was 26%, and 23% reported persistent depression. After adjusting for potential confounders, higher baseline CDAI was associated with both baseline and persistent depression (OR 1.03, 95% CI 1.01–1.05). Female sex was an effect modifier of this relationship (OR 1.04, 95% CI 1.01–1.06). Maintaining a moderate or high CDAI score over 2 years also increased the risk of future depression.Conclusion.Depression in ERA is common and initial high disease activity is associated with the probability of depression and its persistence. This risk seems particularly modified in women with active disease and represents an area for targeted focus and screening. Future studies in ERA are needed to determine if intervening during the “window of opportunity” to control disease activity has the potential to mitigate the development and maintenance of adverse mental health outcomes, including depression.

Objective.To develop a Canadian Rheumatoid Arthritis Core Clinical Dataset (CAN-RACCD) to standardize documentation encouraging high-quality care.Methods.A set of candidate elements was drafted through meetings with 27 rheumatologists, researchers, and patients, and supplemented with focused literature reviews. A 3-round online-modified Delphi consensus process was held with rheumatologists (n = 26), allied health professionals (n = 7), and patients (n = 4); for the remainder there was no demographic information. Participants rated both the importance and feasibility of documenting candidate elements on a Likert scale of 1–9, contributed to an online moderated discussion, and re-rated the elements for inclusion in the CAN-RACCD. Elements were included in the final set if importance and feasibility ratings had a median score of ≥ 6.5 and there was no disagreement among participants.Results.Fifty-five individual elements in 10 subgroups were proposed to the Delphi participants: measures of RA disease activity; dates to calculate waiting times, disease duration, and disease-modifying antirheumatic drug start; comorbidities; smoking status; patient-reported pain and fatigue; physical function; laboratory and radiographic investigations; medications; clinical characteristics; and vaccines. All groups were included in the final set, with the exception of vaccination status. Additionally, 3 individual elements from the smoking subgroup were eliminated with a recommendation to record smoking status as never/ever/current, and 2 elements relating to coping and effect of fatigue were eliminated due to low feasibility and importance ratings.Conclusion.The CAN-RACCD stands as a national recommendation on which data elements should be routinely collected in clinical practice to monitor and support high-quality RA care.

Objective.Disease-modifying antirheumatic drugs (DMARD) have the greatest effect when initiated early. We evaluated the influence of early exposure to DMARD on time to joint replacement surgery among patients with incident rheumatoid arthritis (RA).Method.Using a common protocol, we undertook 2 independent population-based cohort studies of patients with incident RA aged 66 years or older in Ontario (ON) and Quebec (QC) covering the period 2000–2013. We used Cox proportional hazards regression with time-dependent variables measuring duration of drug use in the first year, separately for methotrexate (MTX) and other DMARD, adjusting for baseline demographics, clinical factors, and other potentially confounding drug exposures. Our outcome measure was any joint replacement derived from standardized procedure codes. Adjusted HR and 95% CI were estimated.Results.Among 20,918 ON and 6754 QC patients with RA followed for a median of 4.5 years, 2201 and 494 patients underwent joint replacement surgery for crude event rates of 2.0 and 1.4 per 100 person-years, respectively. Greater cumulative exposure to MTX (HR 0.97, 95% CI 0.95–0.98) and other DMARD (HR 0.98, 95% CI 0.97–0.99) in the first year after diagnosis was associated with longer times to joint replacement in ON, corresponding to a 2–3% decrease in the hazard of surgery with each additional month of early use. Similar results were observed in QC.Conclusion.Greater duration of exposure to DMARD soon after RA diagnosis was associated with delays to joint replacement surgery in both provinces. Early intensive treatment of RA may ultimately reduce demand for joint replacement surgery.

Objective.To determine the proportion of patients with rheumatoid arthritis (RA) under rheumatologic care treated with disease-modifying antirheumatic drugs (DMARD) within 6 months from symptom onset and the components of time to treatment and its predictors.Methods.A historical inception cohort of 339 patients with RA randomly selected from 18 rheumatology practices was audited. The proportion that initiated DMARD treatment within 6 months from symptom onset was estimated using Kaplan-Meier analysis. Time to each component of the care pathway was estimated. Multivariable modeling was used to determine predictors of early treatment using 12 preselected variables available in the clinical charts. Bootstrapping was used to validate the model.Results.Within 6 months from symptom onset, 41% (95% CI 36%−46%) of patients were treated with DMARD. The median time to treatment was 8.4 (interquartile range 3.8−24) months. Events preceding rheumatology referral accounted for 78.1% of the time to treatment. The most prominent predictor of increased time to treatment was a concomitant musculoskeletal condition, such as osteoarthritis or fibromyalgia. The significance of other variables was less consistent across the models investigated. Included variables accounted for 0.69 ± 0.03 of the variability in the model.Conclusion.Fewer than 50% of patients with RA are treated with DMARD within 6 months from symptom onset. Time to referral to rheumatology represents the greatest component delay to treatment. Concomitant musculoskeletal condition was the most prominent predictor of delayed initiation of DMARD. Implications of these and other findings warrant further investigation.

Objective.To describe Canadian clinical practice patterns in the pharmacological management of rheumatoid arthritis (RA) and identify practice variations.Methods.A 44-item pre-guideline needs assessment survey was sent to all members of the Canadian Rheumatology Association (CRA). Descriptive statistics were used to summarize respondent characteristics and practice patterns.Results.Survey respondents (n = 164) reported variations in practice regarding assessment strategies, treatment with disease-modifying antirheumatic drug monotherapy versus combination therapy, methotrexate dosing and escalation, corticosteroid strategies, and optimal use of biologics.Conclusions.Practice variations identified in this pre-guideline needs assessment survey were used to formulate key treatment questions for the development of CRA recommendations.

Objective.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.

Objective.We compared variations among Canadian provinces in rheumatoid arthritis (RA) initiating anti-tumor necrosis factor (TNF) therapy.Methods.Data were obtained from the Optimization of Humira trial (OH) and from the Ontario Biologics Research Initiative (OBRI). Baseline characteristics were compared between regions: Ontario (ON), Quebec (QC), and other provinces (OTH). We compared Ontario OH to OBRI patients who were initiating anti-TNF therapy.Results.In 300 OH patients, mean age was 54.8 years (13.3). There were 151 (50.3%) ON patients, 57 from QC (19%), and 92 from OTH (30.7%). Regional differences were seen in the number of disease-modifying antirheumatic drugs (DMARD) ever taken (ON: 3.8 ± 1.4, QC: 3.1 ± 1.1, OTH: 3.3 ± 1.4; p < 0.001); swollen joint count (SJC; ON: 10.9 ± 5.9, QC: 9.0 ± 4.4, OTH: 11.3 ± 5.6; p = 0.033); tender joint count (TJC; ON: 12.2 ± 7.5, QC: 10.3 ± 5.7, OTH: 14.4 ± 7.6; p = 0.003); 28-joint Disease Activity Score (DAS28; ON: 5.8 ± 1.2, QC: 5.6 ± 1.0, OTH: 6.0 ± 1.1; p = 0.076); and Health Assessment Questionnaire (ON: 1.4 ± 0.7, QC: 1.7 ± 0.7, OTH: 1.5 ± 0.7; p = 0.060). DMARD-ever use differed: methotrexate (ON: 94.7%, QC: 93%, OTH: 84.8%; p = 0.025); leflunomide (ON: 74.8%, QC: 21.1%, OTH: 51.1%; p < 0.001); sulfasalazine (ON: 51%, QC: 38.6%, OTH: 25%; p < 0.001); myochrysine (ON: 9.3%, QC: 0%, OTH: 15.2%; p = 0.008); and hydroxychloroquine (ON: 67.5%, QC: 86%, OTH: 66.3%; p = 0.018). In comparison to ON OH patients, 95 OBRI patients initiating first anti-TNF had lower SJC (p = 0.017), TJC (p = 0.008), and DAS28 (p = 0.05).Conclusion.In Quebec, where access to anti-TNF is less restrictive, patients had lower SJC and TJC. ON used more DMARD, especially leflunomide, as mandated by the provincial government. Both provincial funding criteria and prescribing habits may contribute to differences. Canadian rheumatologists may vary in treatment decisions, but patients generally have similar DAS28 when initiating anti-TNF therapy.

Objective.To develop recommendations for the use of methotrexate (MTX) in patients with rheumatoid arthritis.Methods.Canadian rheumatologists who participated in the international 3e Initiative in Rheumatology (evidence, expertise, exchange) in 2007–2008 formulated 5 unique Canadian questions. A bibliographic team systematically reviewed the relevant literature on these 5 topics. An expert committee consisting of 26 rheumatologists from across Canada was convened, and a set of recommendations was proposed based on the results of systematic reviews combined with expert opinions using a nominal group consensus process.Results.The 5 questions addressed drug interactions, predictors of response, strategies to reduce non-serious side effects, variables to assess clinical response, and incorporating patient preference into decision-making. The systematic review retrieved 93 pertinent articles; this evidence was presented to the expert committee during the interactive workshop. After extensive discussion and voting, a total of 9 recommendations were formulated: 2 on drug interactions, 1 on predictors of response, 2 on strategies to reduce non-serious side effects, 3 on variables to assess clinical response, and 1 on incorporating patient preferences into decision-making. The level of evidence and the strength of recommendations are reported. Agreement among panelists ranged from 85% to 100%.Conclusion.Nine recommendations pertaining to the use of MTX in daily practice were developed using an evidence-based approach followed by expert/physician consensus with high level of agreement.

Worker productivity is a combination of time off work (absenteeism) due to an illness and time at work but with reduced levels of productivity while at work (also known as presenteeism). Both can be gathered with a focus on application as a cost indicator and/or as an outcome state for intervention studies. We review the OMERACT worker productivity groups’ progress in evaluating measures of worker productivity for use in arthritis using the OMERACT filter. Attendees at OMERACT 9 strongly endorsed the importance of work as an outcome in arthritis. Consensus was reached (94% endorsement) for fielding a broader array of indicators of absenteeism. Twenty-one measures of at-work productivity loss, ranging from single item indicators to multidimensional scales, were reviewed for measurement properties. No set of at-work productivity measures was endorsed because of variability in the concepts captured, and the need for a better framework for the measurement of worker productivity that also incorporates contextual issues such as job demands and other paid and unpaid life responsibilities. Progress has been made in this area, revealing an ambivalent set of results that directed us back to the need to further define and then contextualize the measurement of worker productivity.

There is great concern about clearly defining benefit and risk in the context of both drug development and clinical practice. In view of this pressure, the OMERACT Executive identified the need to bring together clinical trialists, pharmacoepidemiologists, clinicians, clinical epidemiologists, statistical experts, and regulatory representatives to discuss different approaches to define risk and perhaps improved ways to express it. Each attendee spoke on a given topic and the group was charged to consider the issue of risk in the context of formally posed questions. This article provides a summary of the presentations and outlines the discussions that followed.

Objective.Indicators of work role functioning (being at work, and being productive while at work) are important outcomes for persons with arthritis. As the worker productivity working group at OMERACT (Outcome Measures in Rheumatology), we sought to provide an evidence base for consensus on standardized instruments to measure worker productivity [both absenteeism and at-work productivity (presenteeism) as well as critical contextual factors].Methods.Literature reviews and primary studies were done and reported to the OMERACT 12 (2014) meeting to build the OMERACT Filter 2.0 evidence for worker productivity outcome measurement instruments. Contextual factor domains that could have an effect on scores on worker productivity instruments were identified by nominal group techniques, and strength of influence was further assessed by literature review.Results.At OMERACT 9 (2008), we identified 6 candidate measures of absenteeism, which received 94% endorsement at the plenary vote. At OMERACT 11 (2012) we received over the required minimum vote of 70% for endorsement of 2 at-work productivity loss measures. During OMERACT 12 (2014), out of 4 measures of at-work productivity loss, 3 (1 global; 2 multiitem) received support as having passed the OMERACT Filter with over 70% of the plenary vote. In addition, 3 contextual factor domains received a 95% vote to explore their validity as core contextual factors: nature of work, work accommodation, and workplace support.Conclusion.Our current recommendations for at-work productivity loss measures are: WALS (Workplace Activity Limitations Scale), WLQ PDmod (Work Limitations Questionnaire with modified physical demands scale), WAI (Work Ability Index), WPS (Arthritis-specific Work Productivity Survey), and WPAI (Work Productivity and Activity Impairment Questionnaire). Our future research focus will shift to confirming core contextual factors to consider in the measurement of worker productivity.

Objective.To describe the trajectories of longitudinal joint disease activity in juvenile idiopathic arthritis (JIA), and to examine associations of clinical and laboratory characteristics with the identified trajectories.Methods.A retrospective cohort study at 2 Canadian centers was performed. The longitudinal trajectories of active joint counts were described in a proof-of-concept study using a latent growth curve analysis. Baseline patient characteristics were compared across trajectory groups.Results.Data were analyzed on 659 children diagnosed with JIA between March 1980 and September 2009. The median age at diagnosis was 10.0 years (interquartile range 3.7–13.4) and 61% (402/659) were female. The International League of Associations for Rheumatology (ILAR) diagnoses were as follows: oligoarthritis (36%), enthesitis-related arthritis (20%), rheumatoid factor (RF)-negative polyarthritis (13%), undifferentiated arthritis (12%), psoriatic arthritis (8%), systemic arthritis (7%), and RF-positive polyarthritis (4%). Based on the trajectories of their active joint counts, the 659 patients were each classified in 1 of 5 latent classes (which can be described as high decreasing, moderate increasing, persistent moderate, persistent low, and minimal joint activity). These latent classes were clinically and statistically distinct from the ILAR categories.Conclusion.In this proof-of-concept study, in which we used an analytic methodology in a novel way, we identified 5 clinically and statistically distinct trajectories of disease course. The subsets of patients within each class were different from those described by the ILAR classification criteria. This successful application of this method supports its use in a chronic disease with a fluctuating course such as JIA. These methods should be expanded for the purposes of predictive modeling.

Objective.The Canadian Rheumatology Association (CRA) has developed recommendations for the pharmacological management of rheumatoid arthritis (RA) with traditional and biologic disease-modifying antirheumatic drugs (DMARD) in 2 parts. Part II, focusing on specific safety aspects of treatment with traditional and biologic DMARD in patients with RA, is reported here.Methods.Key questions were identifieda prioribased on results of a national needs-assessment survey. A systematic review of all clinical practice guidelines and consensus statements regarding treatment with traditional and biologic DMARD in patients with RA published between January 2000 and June 2010 was performed in Medline, Embase, and CINAHL databases, and was supplemented with a “grey literature” search including relevant public health guidelines. Systematic reviews of postmarketing surveillance and RA registry studies were performed to update included guideline literature reviews as appropriate. Guideline quality was independently assessed by 2 reviewers. Guideline characteristics, recommendations, and supporting evidence from observational studies and randomized trials were synthesized into evidence tables. The working group voted on recommendations using a modified Delphi technique.Results.Thirteen recommendations addressing perioperative care, screening for latent tuberculosis infection prior to the initiation of biologic DMARD, optimal vaccination practices, and treatment of RA patients with active or a history of malignancy were developed for rheumatologists, other primary prescribers of RA drug therapies, and RA patients.Conclusion.These recommendations were developed based on a synthesis of international RA and public health guidelines, supporting evidence, and expert consensus in the context of the Canadian health system. They are intended to help promote best practices and improve healthcare delivery for persons with RA.

Objective.To describe early rheumatologic management for newly diagnosed rheumatoid arthritis (RA) in Canada.Methods.A retrospective cohort of 339 randomly selected patients with RA diagnosed from 2001–2003 from 18 rheumatology practices was audited between 2005–2007.Results.The most frequent initial disease-modifying antirheumatic drugs (DMARD) included hydroxychloroquine (55.5%) and methotrexate (40.1%). Initial therapy with multiple DMARD (15.6%) or single DMARD and corticosteroid combinations (30.7%) was infrequent. Formal assessment measures were noted infrequently, including the Health Assessment Questionnaire (34.6%) and Disease Activity Score for 28 joints (8.9%).Conclusion.Initial pharmacotherapy is consistent with guidelines from the period. The infrequent reporting of multiple DMARD combinations and formal assessment measures has implications for current clinical management and warrants contemporary reassessment.

To describe Canadian clinical practice patterns in the pharmacological management of rheumatoid arthritis (RA) and identify practice variations.A 44-item pre-guideline needs assessment survey was sent to all members of the Canadian Rheumatology Association (CRA). Descriptive statistics were used to summarize respondent characteristics and practice patterns.Survey respondents (n = 164) reported variations in practice regarding assessment strategies, treatment with disease-modifying antirheumatic drug monotherapy versus combination therapy, methotrexate dosing and escalation, corticosteroid strategies, and optimal use of biologics.Practice variations identified in this pre-guideline needs assessment survey were used to formulate key treatment questions for the development of CRA recommendations.

Objective.To describe the longterm effectiveness and safety of etanercept in Canadian patients with psoriatic arthritis (PsA), treated over 24 months in clinical practice.Methods.Patients with active PsA (≥ 3 tender and ≥ 3 swollen joints) were recruited from 22 centers. Etanercept was administered at 50 mg/week subcutaneously. In addition to clinical assessment of skin and joint disease, conducted at baseline and at Months 6, 12, 18, and 24, regular patient interviews were conducted by telephone. Patient responses related to health status, disability, and work productivity were scored using the patient global assessment tool, the Health Assessment Questionnaire (HAQ), the Health and Labour Questionnaire (HLQ), and the Fatigue Severity Scale.Results.Out of 110 patients, 71 (65%) maintained etanercept treatment through the end of our study. All clinical measures of disease severity, including joint tenderness/pain, joint swelling, and Psoriasis Area and Severity Index score, improved significantly between baseline and Month 6 of etanercept treatment and remained constant thereafter. By the end of our study, 79% of patients achieved a Psoriatic Arthritis Response Criteria response, and 56% of patients achieved a 0.5-point improvement on HAQ, indicating clinically significant improvement in disability; 14% of patients finished our study free of disability (HAQ = 0). Patients’ work productivity and fatigue improved significantly in parallel with these clinical and functional improvements.Conclusion.Continuous treatment with etanercept over 2 years in a clinical setting improved clinical symptoms of PsA while reducing fatigue, improving work productivity, and ameliorating or eliminating disability.

Objective.Previously, a preliminary patient responder index (RI) in chronic low back pain (CLBP) was developed and validated in 5 placebo-controlled clinical trials. The resulting RI was a > 30% improvement in CLBP and patient global assessment (PGA), and no worsening (< 20%) in the Roland Morris Disability Questionnaire (RMDQ) total score. Our objective was to provide further characterization of the preliminary RI in a trial with an active control.Methods.Data from a 6-week randomized, double-blind study of celecoxib compared to tramadol hydrochloride was analyzed to determine differences by treatment group on the CLBP RI and its components, to compare the CLBP RI with each of its individual components, and to reanalyze the original cutoff points for the responder criteria.Results.Of the celecoxib arm, 50.7%, and of the tramadol hydrochloride arm, 43.7% were classified as responders under the CLBP RI (p = 0.043). The PGA is the most important component in the RI (45% of the sample failed to reach the > 30% improvement criteria on the PGA compared to 34% on the low back pain visual analog scale and only 11% on the RMDQ. The agreement among the CLBP RI with each of its 3 components was largest for the PGA component (κ coefficient 0.849) and smallest for the RMDQ component (κ coefficient 0.207).Conclusion.The RI appears to be particularly sensitive to the cutoff point used for improvement in the PGA component. Further testing of the index in trials with other active comparators is required to gain a fuller understanding of its performance.

Objective.To systematically review the literature on the value of outcome measures to monitor treatment response in patients with rheumatoid arthritis (RA).Methods.Canadian rheumatologists participating in the International 3e (evidence expertise exchange) Initiative formulated the question “Which parameters should be recommended for use in the management of RA patients to assess a clinically meaningful response in clinical practice?”. Searches in 3 electronic databases, Medline, Embase, and Cochrane Central Register of Controlled Trials, yielded no relevant study addressing this question. Experts in the field proposed to extrapolate evidence from 3 randomized controlled trials of systematic monitoring or tight control strategy in the management of RA.Results.Three studies were included in this review. The TICORA study showed that intensive management using systematic monitoring with the Disease Activity Score (DAS) aiming at least low disease activity, monthly followup, and more aggressive disease-modifying antirheumatic drug (DMARD) treatment improves outcomes with higher remission rates (65% vs 16%; p < 0.0001). Fransen, et al demonstrated that targeted therapy aimed at low disease activity (DAS28 < 3.2) led to more changes in DMARD treatment, resulting in a larger number of patients with low disease activity (31% vs 16%; p = 0.028). The CAMERA study showed that systematic monitoring using the objective computer decision program evaluation and monthly followup yielded a greater remission rate (50% vs 37%; p = 0.0001).Conclusion.Systematic monitoring of disease activity, aiming for at least low disease activity, and frequent followup improves outcome in RA.

There is great concern about clearly defining benefit and risk in the context of both drug development and clinical practice. In view of this pressure, the OMERACT Executive identified the need to bring together clinical trialists, pharmacoepidemiologists, clinicians, clinical epidemiologists, statistical experts, and regulatory representatives to discuss different approaches to define risk and perhaps improved ways to express it. Each attendee spoke on a given topic and the group was charged to consider the issue of risk in the context of formally posed questions. This article provides a summary of the presentations and outlines the discussions that followed.

Utility assessment and cost-utility analyses such as costs/quality-adjusted life-years (QALY) are frequently presented to demonstrate the value of new treatment options in rheumatoid arthritis (RA). However, utility indicators require various methods that introduce significant methodological challenges, which directly influence the results and ensuing reimbursement decisions. Our objective was to review and discuss these challenges and the validity of frequently used utility assessment techniques in the context of RA. Coding the intensity of preferences or variations in patient satisfaction in order to assess utility implies extreme mathematical assumptions about a patient's rationality regarding his/her preferences towards different given health states. The construction and assumptions of commonly used "direct approaches" (standard gamble, time tradeoff, visual analog scale) and indirect approaches (EQ5D, HUI, SF6D) are presented. Other approaches such as transformation in utility of data from clinical (Health Assessment Questionnaire) or quality of life instruments ("mapping technique") are analyzed as they appear to generate uncertainty and a wide variation in estimated utility values in the context of RA. Utility assessment and cost-utility analyses in RA, which form the basis of the QALY, are frequently published and often requested by health technology assessment agencies to assist -reimbursement decisions. However, when interpreting the results, the medical community must take into consideration the limitations and significant uncertainty of these approaches. In light of these findings, real cost-effectiveness analyses based on observed clinical outcomes appear to be more robust and reliable to assist decision-making, particularly in the context of RA.

Arthritis is a leading cause of work disability and makes up a significant amount of the socioeconomic cost and health burden to the working age population. We discuss the measurement of worker productivity: that is, absenteeism and presenteeism. Absenteeism refers to the time missed from work due to health reasons and presenteeism refers to the time of impaired performance while at work due to health reasons resulting in productivity loss. While the term absenteeism is commonly used and has several definitions by itself, the current arthritis literature lacks the use of presenteeism as a work outcome measure in describing health states of the workers and for economic costing. Due to advanced medical management and job accommodations that allow workers to stay at work, absenteeism alone may not be enough to give us a complete picture of worker productivity. From our review, we found that the conceptualization and measurement of absenteeism and presenteeism differ. Our research agenda was to carry forward a work outcome measurement that can be used for cost calculation and that can determine levels or states of productivity loss so we can accurately measure the influence of arthritis and advance arthritis care. We recognize the need to perform psychometric testing of work outcome measures and to improve our ability to identify transitions (i.e., move in and out of a productivity state over time) made by workers with arthritis.

One of the greatest obstacles to identifying the most effective therapy for chronic low back pain (CLBP) is the lack of standardized outcome measures for assessing treatment effect in clinical trials. The aim of the OMERACT Special Interest Group was to discuss the development and validation of a preliminary responder index in CLBP.Patient data from 5 clinical trials of celecoxib and valdecoxib use in CLBP were used to assess the reliability and validity of multiple items in the outcome domains of pain, functioning, and overall impression of health. Candidate preliminary responder indices were selected on the basis of effect size, high chi-square test values, and a placebo response rateor = 25%.Candidate indices comprised improvements in single outcome measures and combinations of improvements and/or avoidance of worsening in multiple measures. The preliminary choice for the responder index was at least 30% improvement in pain, with an improvement of at least 30% in patient global assessment and no worsening in function.Further studies are needed to refine a responder index for CLBP trials that is clinically relevant, reliable, and easy to administer for standardizing assessments across clinical trials.

While there is strong evidence supporting a multidisciplinary team approach in arthritis management, access and use are hindered by limited human and financial resources. To safeguard the provision of comprehensive care throughout the disease trajectory, alternative care models are being developed. Three promising arthritis care models include the use of information technology and telemedicine, patient initiated care, and extended roles of health professionals. Future research projects should focus on: (1) the cost-effectiveness of information technology for exchange of patient-based data and education and management support; (2) the characteristics and needs of patients who can versus those who cannot self-manage; (3) strategies to improve access to care for patients with early arthritis, such as extending roles of health professionals to include triage; and (4) further structuring and standardizing rheumatology training of nursing and allied health professionals.

To revisit our previous evidence-based recommendations on the appropriate prescription of nonsteroidal antiinflammatory drugs (NSAID) with particular emphasis on cyclooxygenase-2 selective inhibitors (coxibs).Needs assessments were conducted among Canadian physicians to determine their educational needs surrounding NSAID/coxibs. A survey of patients with arthritis was also conducted. Consensus participants reviewed articles relating to NSAID/coxibs in peer-reviewed journals between January 2000 and December 2004. At the consensus meeting, held January 21-23, 2005, participants discussed selected topics, after which recommendations were formulated and debated. Results. At the time of the meeting, it was agreed that emerging cardiovascular data were not clear enough to decide whether unanticipated cardiovascular events associated with coxibs represent a class effect or an effect of an individual drug. However, publications that appeared shortly after the meeting, as well as data presented at both the Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee of the US Food and Drug Administration, February 16-18, 2005, and Health Canada's Expert Advisory Panel on the Safety of Cox-2 Selective NSAID, June 9-10, 2005, clarified that all available coxibs do carry some degree of cardiovascular risk, denoting a class effect. Our consensus group made the following specific recommendations: (1) Patients should be fully informed about treatment options, including the need to balance between cardiovascular risks and gastrointestinal (GI) benefits of NSAID/coxibs. (2) Coxibs are as effective as nonselective NSAID and superior to acetaminophen for the symptoms of arthritis. Topical NSAID may also be beneficial. (3) Coxibs are associated with fewer severe GI complications than nonselective NSAID. A proton pump inhibitor (PPI) should be prescribed if an NSAID must be used in a patient at increased GI risk. (4) The renal/blood pressure (BP) impact of coxibs is similar to that of NSAID. (5) In individuals at risk, creatinine clearance and BP should be determined at baseline and shortly after treatment begins. (6) In the geriatric population, use of nonpharmacological therapies should be maximized, and special caution is required before prescribing oral NSAID/coxibs. (7) Patients taking rofecoxib have been shown to have an increased risk of cardiovascular events. Current data suggest that this increased cardiovascular risk may be an effect of the NSAID/coxib class. (8) Although the data are limited, coxibs may be more cost-effective for patients at high GI risk than nonselective NSAID plus proprietary PPI.Coxibs continue to be an option in the treatment armamentarium. Given the evolving cardiovascular information, physicians and patients should weigh the benefits and risks of NSAID/coxib treatment. This concern emphasizes the need to routinely reassess patients' risks. These recommendations, which were formulated according to the Appraisal of Guidelines for Research and Evaluation, are intended to be used as guidelines to supplement, but not replace, the physician's judgment in clinical decision-making.