Cheryl Barnabe

Systematic review and meta-analysis: Anti–tumor necrosis factor α therapy and cardiovascular events in rheumatoid arthritis

Control of rheumatoid arthritis (RA) may reduce the risk of cardiovascular events. We sought to systematically assess the association between anti–tumor necrosis factor α (anti‐TNFα) therapy in RA and cardiovascular event rates.

Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis

Objective To compare methotrexate based disease modifying antirheumatic drug (DMARD) treatments for rheumatoid arthritis in patients naive to or with an inadequate response to methotrexate. Design Systematic review and Bayesian random effects network meta-analysis of trials assessing methotrexate used alone or in combination with other conventional synthetic DMARDs, biologic drugs, or tofacitinib in adult patients with rheumatoid arthritis. Data sources Trials were identified from Medline, Embase, and Central databases from inception to 19 January 2016; abstracts from two major rheumatology meetings from 2009 to 2015; two trial registers; and hand searches of Cochrane reviews. Study selection criteria Randomized or quasi-randomized trials that compared methotrexate with any other DMARD or combination of DMARDs and contributed to the network of evidence between the treatments of interest. Main outcomes American College of Rheumatology (ACR) 50 response (major clinical improvement), radiographic progression, and withdrawals due to adverse events. A comparison between two treatments was considered statistically significant if its credible interval excluded the null effect, indicating >97.5% probability that one treatment was superior. Results 158 trials were included, with between 10 and 53 trials available for each outcome. In methotrexate naive patients, several treatments were statistically superior to oral methotrexate for ACR50 response: sulfasalazine and hydroxychloroquine (“triple therapy”), several biologics (abatacept, adalimumab, etanercept, infliximab, rituximab, tocilizumab), and tofacitinib. The estimated probability of ACR50 response was similar between these treatments (range 56-67%), compared with 41% with methotrexate. Methotrexate combined with adalimumab, etanercept, certolizumab, or infliximab was statistically superior to oral methotrexate for inhibiting radiographic progression, but the estimated mean change over one year with all treatments was less than the minimal clinically important difference of 5 units on the Sharp-van der Heijde scale. Triple therapy had statistically fewer withdrawals due to adverse events than methotrexate plus infliximab. After an inadequate response to methotrexate, several treatments were statistically superior to oral methotrexate for ACR50 response: triple therapy, methotrexate plus hydroxychloroquine, methotrexate plus leflunomide, methotrexate plus intramuscular gold, methotrexate plus most biologics, and methotrexate plus tofacitinib. The probability of response was 61% with triple therapy and ranged widely (27-70%) with other treatments. No treatment was statistically superior to oral methotrexate for inhibiting radiographic progression. Methotrexate plus abatacept had a statistically lower rate of withdrawals due to adverse events than several treatments. Conclusions Triple therapy (methotrexate plus sulfasalazine plus hydroxychloroquine) and most regimens combining biologic DMARDs with methotrexate were effective in controlling disease activity, and all were generally well tolerated in both methotrexate naive and methotrexate exposed patients.

Effect of tumor necrosis factor alpha inhibition on bone density and turnover markers in patients with rheumatoid arthritis and spondyloarthropathy.

OBJECTIVES Anti-tumor necrosis factor-alpha (TNFalpha) therapy has proven efficacious in improving both disease activity and focal bone erosions in patients with rheumatoid arthritis (RA) and spondyloarthopathies. We review the current literature reporting on the effect of anti-TNFalpha on bone density as measured by dual energy radiograph absorptiometry at the lumbar spine and hip, as well as markers of bone turnover and resorption, in patients using anti-TNFalpha for rheumatic disease indications. METHODS A PubMed search, as well as manual search of related articles and references of articles retrieved, was performed to identify all studies pertaining to the effect of anti-TNFalpha therapy on bone mineral density (BMD) and bone turnover markers. RESULTS In RA, 4 studies (238 patients) showed a stabilization or increase of BMD at the spine (up to 2.8%) or hip (up to 13.1%), with only 1 negative study in 48 patients (decline of 3.2% at the spine and 2.7% at the hip). In spondyloarthopathies, 3 studies (75 patients) all demonstrated an increase in BMD at the lumbar spine (3.2-3.6%) and at the hip (1.8-2.2%). Changes in markers of bone formation and bone resorption were heterogeneous but in general represented a modest increase in formation and decline in resorption. CONCLUSIONS In general, anti-TNFalpha therapy has a beneficial effect on bone density and bone turnover markers. Retrieved studies were heterogeneous with regards to patients studied, underlying risks for osteoporosis, and supplemental therapy, which may limit the findings of the true effect of anti-TNFalpha therapy on bone.

Risk Factors for Infection Following Total Joint Arthroplasty in Rheumatoid Arthritis

Objectives: Determine risk factors for infection following hip or knee total joint arthroplasty in patients with rheumatoid arthritis. Methods: All rheumatoid arthritis patients with a hip or knee arthroplasty between years 2000 and 2010 were identified from population-based administrative data from the Calgary Zone of Alberta Health Services. Clinical data from patient charts during the hospital admission and during a one year follow-up period were extracted to identify incident infections. Results: We identified 381 eligible procedures performed in 259 patients (72.2% female, mean age 63.3 years, mean body mass index 27.6 kg/m2). Patient comorbidities were hypertension (43.2%), diabetes (10.4%), coronary artery disease (13.9%), smoking (10.8%) and obesity (32%). Few infectious complications occurred: surgical site infections occurred within the first year after 5 procedures (2 joint space infections, 3 deep incisional infections). Infections of non-surgical sites (urinary tract, skin or respiratory, n=4) complicated the hospital admission. The odds ratio for any post-arthroplasty infection was increased in patients using prednisone doses exceeding 15 mg/day (OR 21.0, 95%CI 3.5-127.2, p=<0.001), underweight patients (OR 6.0, 95%CI 1.2-30.9, p=0.033) and those with known coronary artery disease (OR 5.1, 95%CI 1.3-19.8, p=0.017). Types of disease-modifying therapy, age, sex, and other comorbidities were not associated with an increased risk for infection. Conclusion: Steroid doses over 15 mg/day, being underweight and having coronary artery disease were associated with significant increases in the risk of post-arthroplasty infection in rheumatoid arthritis. Maximal tapering of prednisone and comorbidity risk reduction must be addressed in the peri-operative management strategy.

Sex Differences in Pain Scores and Localization in Inflammatory Arthritis: A Systematic Review and Metaanalysis

Objective. To systematically identify and examine reports of sex-stratified pain measurements in patients with inflammatory arthritis. Methods. Data sources included PubMed (1950 to April 2010), Embase (1980 to April 2010), and manual searches of reference lists and conference abstracts. We included cohort studies and randomized trials comparing pain scores, treatment efficacy at reducing pain, or pain localization, between females and males with inflammatory arthritis [rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis, and reactive arthritis]. Results. Twenty-six cohorts and 1 randomized trial reported sex-stratified pain scores, and all but 1 cohort identified worse pain scores at enrollment in females. In a metaanalysis of mean visual analog scale (VAS) scores (0 to 10) in 16 RA cohort studies (reporting on 21,612 females and 6871 males), the standardized mean difference in VAS was 0.21 (95% CI 0.16, 0.26). Treatment with disease-modifying therapy results in improvement in mean scores for both sexes; however, female absolute scores remain higher. In 12 spondyloarthropathy cohorts reporting pain localization, females develop more peripheral arthritis during their disease course (68.9% vs 51.2%) but less inflammatory back pain (50.6% vs 66.4%). Conclusion. We identified important sex differences in pain scores in inflammatory arthritis, with higher pain levels in females. In spondyloarthritis, females develop more peripheral arthritis and have less frequent spinal involvement compared to males. These differences may affect a clinician’s perception of disease severity and activity, and thus influence management decisions.

High-resolution Peripheral Quantitative Computed Tomography Imaging Protocol for Metacarpophalangeal Joints in Inflammatory Arthritis: The SPECTRA Collaboration

To the Editor: High-resolution peripheral quantitative computed tomography (HR-pQCT; Scanco Medical AG, Bruttisellen, Switzerland) is a novel peripheral CT instrument capable of accurately and reproducibly imaging bone microstructure at great resolution (isotropic voxel dimension of 82 μm). It provides precise measures of 3-D microstructural morphometric details and volumetric density of the cortical and trabecular components of bone (Figure 1), with minimal radiation exposure (< 3 μSv per scan)1. Therefore, HR-pQCT has the potential to identify and quantify early microstructural bone quality changes before permanent bone damage has occurred. To date, HR-pQCT has been used to assess bone quality in a variety of metabolic bone conditions. Image acquisition and analysis protocols are well defined for the … Address correspondence to Dr. C. Barnabe, 3330 Hospital Dr. NW, Calgary, Alberta T2N 4N1, Canada. E-mail: ccbarnab{at}ucalgary.ca

Prevalence of systemic lupus erythematosus and systemic sclerosis in the First Nations population of Alberta, Canada

To estimate the population‐based prevalence of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) in Alberta, Canada, stratified by First Nations status.

Canadian Pregnancy Outcomes in Rheumatoid Arthritis and Systemic Lupus Erythematosus

Objective. To describe obstetrical and neonatal outcomes in Canadian women with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Methods. An administrative database of hospitalizations for neonatal delivery (1998–2009) from Calgary, Alberta was searched to identify women with RA (38 pregnancies) or SLE (95 pregnancies), and women from the general population matched on maternal age and year of delivery (150 and 375 pregnancies, resp.). Conditional logistic regression was used to calculate odds ratios (OR) for maternal and neonatal outcomes, adjusting for parity. Results. Women with SLE had increased odds for preeclampsia or eclampsia (SLE OR 2.16 (95% CI 1.10–4.21; P = 0.024); RA OR 2.33 (95% CI 0.76–7.14; P = 0.138)). Women with SLE had increased odds for cesarean section after adjustment for dysfunctional labour, instrumentation and previous cesarean section (OR 3.47 (95% CI 1.67–7.22; P < 0.001)). Neonates born to women with SLE had increased odds of prematurity (SLE OR 6.17 (95% CI 3.28–11.58; P < 0.001); RA OR 2.66 (95% CI 0.90–7.84; P = 0.076)) and of SGA (SLE OR 2.54 (95% CI 1.42–4.55; P = 0.002); RA OR 2.18 (95% CI 0.84–5.66; P = 0.108)) after adjusting for maternal hypertension. There was no excess risk of congenital defects in neonates. Conclusions. There is increased obstetrical and neonatal morbidity in Canadian women with RA or SLE.

Healthcare service utilisation costs are reduced when rheumatoid arthritis patients achieve sustained remission

Objective Determine healthcare service utilisation costs among patients using biological therapies for rheumatoid arthritis (RA), considering the magnitude and duration of patient response achieved. Methods Clinical data from the Alberta Biologics Pharmacosurveillance Program (ABioPharm) was linked with provincial physician billing claims, outpatient visits and hospitalisations. The annual mean healthcare service utilisation costs (total, RA-attributable, non-RA attributable) were estimated for patients during the best disease activity level reached during treatment. Results Of 1086 patients: 16% achieved DAS28 remission >1 year, 37% had a DAS28 remission period <1 year, 13% had a low disease activity (LDA) period <1 year and 31% had persistent moderate or high disease activity. Mean annual healthcare service utilisation cost savings for those in sustained remission was

The Impact of Obesity on Remission and Disease Activity in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

2391 (95% CI 1437 to 3909, p<0.001) and