Comparison of tocilizumab as monotherapy or with add-on disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and inadequate responses to previous treatments: an open-label study close to clinical practice

This was an exploratory analysis comparing the safety and efficacy of tocilizumab monotherapy with those of tocilizumab in combination with disease-modifying anti-rheumatic drugs (DMARDs). Data were from a single-arm, nonrandomized, open-label, 24-week study in patients with rheumatoid arthritis in which patients with inadequate responses to DMARDs or tumor necrosis factor-α inhibitors received tocilizumab 8 mg/kg intravenously every 4 weeks plus methotrexate/other DMARD(s) combination therapy. If they were intolerant of methotrexate/other DMARD, patients received tocilizumab monotherapy. Effectiveness endpoints included American College of Rheumatology (ACR) responses (ACR20/50/70/90) and disease activity score using 28 joints (DAS28). Of 1,681 patients, 239 received tocilizumab monotherapy, and 1,442 received combination therapy. Methotrexate was the most common DMARD (79 %) used in combination therapy. The frequency of adverse events (AEs), serious AEs, and AEs leading to withdrawal were similar between tocilizumab monotherapy (82.4, 7.9, and 5.4 %, respectively) and combination therapy (76.6, 7.8, and 5.1 %, respectively). No differences in ACR20/50/70/90 responses were observed between treatment groups (66.9 %/43.5 %/23.8 %/10.0 % vs 66.9 %/47.2 %/26.8 %/8.5 %, respectively; p > 0.12 for all individual comparisons, including ACR50 propensity score analyses). The decrease in DAS28 was also similar between treatment groups (mean ± standard deviation: −3.41 ± 1.49 for tocilizumab monotherapy vs −3.43 ± 1.43 for combination therapy; p > 0.33 all analyses, including propensity score analyses). Tocilizumab had a comparable safety profile, and was similarly effective, when used as monotherapy or in combination with DMARDs in a broad population of patients with rheumatoid arthritis.

     

Utility and feasibility of musculoskeletal ultrasonography (MSK US) in rheumatology practice in Canada: needs assessment

The utility of musculoskeletal ultrasound (MSK US) is being extensively explored and evaluated amongst European rheumatologists. However, utilization of MSK US by rheumatologists in Canada is much less common. This study aimed to evaluate the current use of MSK US in Canadian rheumatology practice, to determine beliefs and attitudes towards MSK US, and to determine factors that may encourage or limit its use. A 13-question needs assessment questionnaire was developed. All Canadian rheumatologists were invited via e-mail to participate in the survey. The overall response rate was 156/470 (33%). Fifty-one percent of participants used MSK US in their clinical practice. Lack of training appeared to be the main obstacle to its current use. Eighty-three percent believed that MSK US should be performed by rheumatologists and expressed a willingness to learn the technique. Skills offering greatest clinical utility were the assessment of inflammatory arthritis in small joints (i.e., hands (metacarpophalyngeal and proximal interphalangeal joints), wrists, feet (metatarsophalyngeal), shoulders, and ankles. Limited available time, equipment costs, and difficulties with billing were the main obstacles to MSK US utilization in the clinical setting. There is a great level of interest in learning and applying MSK US in Canadian rheumatology practice. The balance between added clinical value and lack of remuneration, equipment associated costs, and time to complete training is the major limiting factor influencing rheumatologists' willingness to take on MSK US. Training programs must be relevant to rheumatologists' needs before MSK US will be adopted into routine clinical practice in Canada.     

Factors associated with time to diagnosis in early rheumatoid arthritis

Early diagnosis and treatment yield optimal outcomes in rheumatoid arthritis (RA); thus, barriers to disease recognition must be identified and addressed. We determined the impact of sociodemographic factors, medical comorbidities, family history, and disease severity at onset on the time to diagnosis in early RA. The Canadian early ArThritis CoHort study data on 1,142 early RA patients were analyzed for predictors of time to diagnosis using regression analysis. Sociodemographic factors (age, sex, income strata, education, ethnicity), measures of disease activity (joint counts, DAS28 score, acute-phase reactants, patient global evaluation, function), family history, serology, chronic musculoskeletal and mental health conditions, and obesity at diagnosis were considered. In multivariate linear regression analysis, more swollen joints (β = ?0.047 per joint, 95 % CI ?0.085, ?0.010, p = 0.014), higher erythrocyte sedimentation rate (ESR) (β = ?0.012 per 1 mm/h, 95 % CI ?0.022, ?0.002, p = 0.0018), and worse patient global scores (β = ?0.082 per 1 unit on a visual analogue scale, 95 % CI ?0.158, ?0.006, p = 0.034) at baseline predicted a shorter time to diagnosis. Anti-cyclic citrullinated peptide (anti-CCP) antibody positivity (β = 0.688, 95 % CI 0.261, 1.115, p = 0.002) and low income (annual <$20,000 β = 1.185, 95 % CI 0.227, 2.143, p = 0.015; annual $20,000–50,000 β = 0.933, 95 % CI 0.069, 1.798, p = 0.034) increased time to diagnosis. In the logistic regression models, the odds of being diagnosed within 6 months of symptom onset were increased for each swollen joint present [odds ratio (OR) 1.04, 95 % CI 1.02–1.06 per joint], each 1 mm/h elevation in the ESR (OR 1.01, 95 % CI 1.00–1.02), and decreased for patients who were either rheumatoid factor or anti-CCP positive compared to both factors being negative (OR 0.68, 95 % CI 0.51–0.91). Higher disease activity results in a more rapid diagnosis for Canadian patients with early RA, but those with lower income have delays in diagnosis. Strategies to identify patients with a less severe disease presentation and in lower socioeconomic strata are needed to ensure equal opportunity for optimal management.     

Are the 2002 American College of Rheumatology guidelines for the management of rheumatoid arthritis being followed in Canada's largest academic rheumatology center?

OBJECTIVE: To determine whether rheumatologists working in Canada's largest academic rheumatology center (University Health Network/Mount Sinai Hospital) adhere to the 2002 American College of Rheumatology (ACR) guidelines for the management of rheumatoid arthritis (RA). METHODS: Ten patients with RA seen between January 1 and December 30, 2005, were randomly selected from each rheumatologist. A standardized form was used to verify whether the following items were collected at each visit: (1) degree of joint pain, (2) duration of morning stiffness, (3) degree of fatigue, (4) number of tender/swollen joints, and (5) assessment of function. Items recommended for periodic assessment were also collected and included: (1) examination for joint damage, (2) erythrocyte sedimentation rate and/or C-reactive protein, and (3) radiographic assessment of joint damage (radiograph/magnetic resonance imaging). RESULTS: One hundred thirty charts and 313 total visits met inclusion criteria. No rheumatologist consistently assessed each ACR item. Of the recommended items, tender and swollen joint counts and pain were most commonly assessed (95%, 95%, and 69%, respectively). Functional assessment, morning stiffness, and fatigue were least commonly reported (48%, 46%, and 33%, respectively). Items recommended for periodic assessment were not regularly recorded. There was a trend for the recommended items to be reported more regularly for new patients, patients taking a disease modifying antirheumatic drug (DMARD), and patients for whom a DMARD was added or increased in dosage. CONCLUSION: Rheumatologists follow many but not all of the recommendations included in the revised ACR guidelines. The reasons underlying the noncompliance to some of the recommendations are not fully understood. In order to improve the adoption of future clinical practice guidelines, the ACR may have to plan specific dissemination and implementation strategies and fund studies to formally assess the effect of guideline use on clinical outcomes.     

Early rheumatoid arthritis: The performance of the 2010 ACR/EULAR criteria for diagnosing RA

New classification criteria for rheumatoid arthritis (RA) were presented by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) in 2010, aiming for early identification of patients at risk of developing persistent and erosive arthritis. Since their publication, the criteria have been extensively validated against several reference standards, but there is still debate regarding how the criteria should be implemented in studies and clinical care. We present an overview of the published validation studies and discuss the strengths and limitations of the classification criteria, as well as whether the criteria are ready for diagnostic purposes in clinical practice.