Stephanie Keeling

The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis

The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010-2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk.

Evidence-based Recommendations for the Management of Comorbidities in Rheumatoid Arthritis, Psoriasis, and Psoriatic Arthritis: Expert Opinion of the Canadian Dermatology-Rheumatology Comorbidity Initiative

Objective. Comorbidities such as cardiovascular diseases (CVD), cancer, osteoporosis, and depression are often underrecognized in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis (PsO). Recommendations may improve identification and treatment of comorbidities. The Canadian Dermatology-Rheumatology Comorbidity Initiative reviewed the literature to develop practical evidence-based recommendations for management of comorbidities in patients with RA, PsA, and PsO. Methods. Eight main topics regarding comorbidities in RA, PsA, and PsO were developed. MEDLINE, EMBASE, and the Cochrane Library (1960–12/2012), together with abstracts from major rheumatology and dermatology congresses (2010–2012), were searched for relevant publications. Selected articles were analyzed and metaanalyses performed whenever possible. A meeting including rheumatologists, dermatologists, trainees/fellows, and invited experts was held to develop consensus-based recommendations using a Delphi process with prespecified cutoff agreement. Level of agreement was measured using a 10-point Likert scale (1 = no agreement, 10 = full agreement) and the potential effect of recommendations on daily clinical practice was considered. Grade of recommendation (ranging from A to D) was determined according to the Oxford Centre for Evidence-Based Medicine evidence levels. Results. A total of 17,575 articles were identified, of which 407 were reviewed. Recommendations were synthesized into 19 final recommendations ranging mainly from grade C to D, and relating to a large spectrum of comorbidities observed in clinical practice: CVD, obesity, osteoporosis, depression, infections, and cancer. Level of agreement ranged from 80.9% to 95.8%. Conclusion. These practical evidence-based recommendations can guide management of comorbidities in patients with RA, PsA, and PsO and optimize outcomes.

Effect of biologics on depressive symptoms in patients with psoriasis: a systematic review.

Twenty to fifty percent of patients with psoriasis have depressive symptoms.

Development of Cardiovascular Quality Indicators for Rheumatoid Arthritis: Results from an International Expert Panel Using a Novel Online Process

Objective. Patients with rheumatoid arthritis (RA) have a high risk of premature cardiovascular disease (CVD). We developed CVD quality indicators (QI) for screening and use in rheumatology clinics. Methods. A systematic review was conducted of the literature on CVD risk reduction in RA and the general population. Based on the best practices identified from this review, a draft set of 12 candidate QI were presented to a Canadian panel of rheumatologists and cardiologists (n = 6) from 3 academic centers to achieve consensus on the QI specifications. The resulting 11 QI were then evaluated by an online modified-Delphi panel of multidisciplinary health professionals and patients (n = 43) to determine their relevance, validity, and feasibility in 3 rounds of online voting and threaded discussion using a modified RAND/University of California, Los Angeles Appropriateness Methodology. Results. Response rates for the online panel were 86%. All 11 QI were rated as highly relevant, valid, and feasible (median rating ≥ 7 on a 1–9 scale), with no significant disagreement. The final QI set addresses the following themes: communication to primary care about increased CV risk in RA; CV risk assessment; defining smoking status and providing cessation counseling; screening and addressing hypertension, dyslipidemia, and diabetes; exercise recommendations; body mass index screening and lifestyle counseling; minimizing corticosteroid use; and communicating to patients at high risk of CVD about the risks/benefits of nonsteroidal antiinflammatory drugs. Conclusion. Eleven QI for CVD care in patients with RA have been developed and are rated as highly relevant, valid, and feasible by an international multidisciplinary panel.

Measuring Multiple Etanercept Levels in the Breast Milk of a Nursing Mother with Rheumatoid Arthritis

To the Editor: A recent report of declining etanercept levels in infant serum postpartum and negligible amounts in breast milk suggested that etanercept may be a safe treatment option for postpartum patients with rheumatoid arthritis (RA)1. Limited data exist detailing breast milk concentrations of etanercept at 25 mg and 50 mg doses over a longer period of time. We describe levels of etanercept in breast milk of an RA nursing mother performed at her request. A 34-year-old etanercept-naive mother with RA delivered a healthy 3.4 kilogram female infant full-term with no abnormalities or complications, maintaining remission … Address correspondence to Dr. Keeling; E-mail: stephanie.keeling{at}ualberta.ca

Meta-analysis of tumor necrosis factor inhibitors and glucocorticoids on bone density in rheumatoid arthritis and ankylosing spondylitis trials.

To examine the impact of antirheumatic drugs on bone mineral density (BMD) in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis using a systematic review.

Lack of cardiovascular risk assessment in inflammatory arthritis and systemic lupus erythematosus patients at a tertiary care center

The purpose of this study is to evaluate cardiovascular risk assessment at a Canadian rheumatology center and describe the cardiovascular risk of inflammatory arthritis (IA) and systemic lupus erythematosus (SLE) patients using the Framingham risk score. A retrospective chart review of 504 patients attending nine rheumatology practices at the University of Alberta Hospital was performed. A pre-specified case report form detailed patient demographics, cardiac risk factors, variables for the Framingham 2008 score, disease activity, and medication use. In this group of 504 patients, 64 (12.7%) had SLE (male (M) to female (F) ratio = 60:4) and 440 (87.3%) had an IA (M to F ratio = 117:323). Of the SLE patients, 31 (48.4%) met four or more American College of Rheumatology (ACR) criteria, 33 (51.6%) had less than four ACR criteria. Of the IA patients, 156 (35.5%) were CCP positive and 257 (58.4%) were RF positive. Utilizing the chart data, retrospective Framingham risk scores were calculable for one (1.6%) SLE patient and three (0.68%) IA patients. The most common cardiac risk factors not documented in the medical records of both the SLE and IA patients included: (1) positive family history of MI, (2) diabetes, and (3) lipid status. The blood pressure was more frequently documented in the SLE patients (93.8%) compared to the IA patients (56.1%). While traditional cardiac risk factors only partially contribute to the increased cardiovascular risk in these patients, cardiovascular risk assessment was suboptimally performed amongst a large group of rheumatologists. A dedicated cardiovascular risk reduction clinic for inflammatory rheumatic diseases has been established at this site to fulfill this need and evaluate treatment strategies.

Psoriasis and Smoking A Systematic Literature Review and Meta-Analysis With Qualitative Analysis of Effect of Smoking on Psoriasis Severity

Background: Smoking has been associated with psoriasis prevalence and severity. Objective: To evaluate prevalence of smoking in patients with psoriasis and to examine the relationship between smoking and psoriasis severity. Methods: MEDLINE, EMBASE, and Cochrane databases (1960-2012) and conference proceedings (2010-2012) were systematically searched using keywords relevant to psoriasis and smoking. Controlled studies addressing psoriasis and smoking status were included. A meta-analysis for the relative risk of smoking in psoriasis patients was performed. Results: Meta-analysis identified a significant association between smoking and psoriasis with a relative risk of 1.88 (95% CI, 1.66-2.13) for smoking in patients with psoriasis versus patients without psoriasis. Eight articles of 11 with data on smoking and psoriasis severity suggested that severity increases with smoking status. Conclusions: This literature review is in favor of a positive association between the prevalence of smoking and psoriasis as well as an association between smoking and severity of psoriasis.

Preliminary Validation of a Self-reported Screening Questionnaire for Inflammatory Back Pain

Objective. Inflammatory back pain (IBP) is an important feature of axial spondyloarthritis (SpA) that is poorly recognized in primary care, perhaps delaying diagnosis of SpA. We aimed to develop and validate a self-report questionnaire using important domains reported by patients with IBP. Methods. We developed a 6-item questionnaire assessing spinal/hip stiffness, nocturnal pain, diurnal variation, effects of exercise/rest, and peripheral joint pain/swelling. This was compared with the Calin questionnaire and the domains comprising the Assessment of Spondyloarthritis International Society (ASAS) criteria for IBP in 220 patients with established axial SpA and 66 patients with mechanical back pain followed in tertiary care rheumatology clinics. The classification utility of each item was evaluated using sensitivity, specificity, and likelihood ratio (LR). Multivariable logistic regression was used to analyze different combinations of items to develop candidate scoring systems. Results. The single item “diurnal variation” had the highest combination of sensitivity (49%) and specificity (92%) for IBP (positive LR 5.95, 95% CI 2.54–13.94), outperforming the Calin and ASAS IBP criteria, which had sensitivities of 83% and 59%, specificities 42% and 66%, positive LR 1.42 and 1.72, negative LR 0.41 and 0.62, respectively. Classification utility of this item was even higher in SpA patients with disease duration < 6 years (sensitivity 48%, specificity 96%, positive LR 12, negative LR 0.54). The other 5 items did not improve classification utility in any combination. Conclusion. Assessment of a single self-reported item, “diurnal variation,” had substantial classification utility for IBP. This domain is not addressed in existing criteria for IBP, indicating a potentially important omission.

Successful Switch of Patients with Rheumatoid Arthritis Developing Anti-tumor Necrosis Factor (anti-TNF)-induced Lupus to Another Anti-TNF Agent

Patient 1. A 43-year-old woman with a 15-year history of seropositive rheumatoid arthritis (RA) achieved remission when treated with adalimum ab 50 mg biweekly 8 years ago. Adalimumab was increased to 50 mg week ly when she developed an arthritis flare. Her arthritis worsened and she developed severe pleuritis but no other lupus features. Laboratory investi gations revealed anti-dsDNA antibodies that were not present in her preadalimumab antibody profile and persistence of anti-SSA antibodies that were present prior to adalimumab. A diagnosis of adalimumab-induced lupus was made and adalimumab was discontinued. Her symptoms resolved while taking prednisone 60 mg daily. One month later, she was asympto matic on a tapering course of prednisone. Her antibody profile at that time remained positive for anti-SSA antibodies but was negative for anti-dsDNA antibodies. She had a flare of RA off prednisone; therefore, she was treated with etanercept 25 mg twice weekly. The disease went into remission and has remained so for the past 4 years. Her antibody profile remains positive for anti-SSA antibodies and negative for anti-dsDNA antibodies. Patient 2. A 58-year-old woman with a 20-year history of seropositive RA was treated with infliximab 3 mg/kg in addition to leflunomide 20 mg/day. Ten weeks after starting infliximab she developed oral ulcers and increased joint symptoms with, active synovitis on examination. Laboratory investi gations revealed anti-dsDNA antibodies that were not present in her preinfliximab antibody profile. Her extractable nuclear antigen (ENA) profile was negative. She was diagnosed with infliximab-induced lupus and the infliximab was discontinued. She was maintained on leflunomide 20 mg/day. Her joint symptoms improved and oral ulcers resolved 2 months later. A repeat antibody profile showed that her ENA remained negative and her anti-dsDNA antibodies were negative. Her disease remained under control for 3 years taking leflunomide. She subsequently developed a dis ease flare and etanercept 25 mg twice weekly was added, with resolution of her synovitis. Two and a half years later she remains asymptomatic and her ENA and anti-dsDNA antibody profiles are negative. Treatment of patients with active RA who have had anti-TNF-induced lupus with a second TNF inhibitor should be monitored closely. Anti -TNF -induced lupus may be a class effect, as it has been reported to occur with all forms of this therapy. It is recognized that antinuclear anti bodies occur in association with anti-TNF therapies but anti-TNF-induced lupus is uncommon. In one study of RA patients treated with one of 3 anti -TNF therapies, infliximab, etanercept, and adalimumab were all shown to cause the development of anti-nucleosome antibodies, antibodies that have a role in the diagnosis and followup of patients with systemic lupus erythematosus 3 . However, the investigators comment that the devel opment of anti-TNF-induced lupus is uncommon with these agents. In another study over 50% of infliximab-treated patients and 10% of etaner cept-treated patients developed anti-dsDNA antibodies, suggesting differ ences in immunogenicity between the drugs 4. This observation is of inter est in view of the data reported in another study of anti-TNF-induced lupus that shows infliximab is associated with anti-TNF-induced lupus more fre quently than etanercept or adalimumab 5 . Anti-TNF-induced lupus differs from the classic drug-induced lupus in that it is characterized by a greater frequency of skin involvement, the pres ence of anti-dsDNA antibodies, and the lack of anti-histone antibodies.