Alexandra McFarlane

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.

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.

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.

The Value of Macrolide-Based Regimens for Community-Acquired Pneumonia

Macrolide antimicrobials are commonly prescribed, specifically for the treatment of respiratory tract infections. Although still effective, the development of widespread macrolide resistance has limited their use. Aside from their antimicrobial effects, macrolides are also known to possess immune-modulatory properties which may confer a survival benefit in both acute and chronic inflammatory states. This review discusses the efficacy, potential mechanisms, and adverse effects of macrolide therapy specifically in community-acquired pneumonia in outpatients, hospitalized ward patients, and those requiring intensive care unit admission. Challenges for ongoing research in this field are discussed and treatment recommendations offered.

Response to: ‘Drugs and cardiovascular risk in inflammatory arthritis: another case of glucocorticoid-bashing?’ by Dr Boers

We thank Dr Boers for the interesting comments1 on our paper2. First, the decision to exclude studies reporting less than 400 patients was made after noticing that most of these studies had less than 1 year of follow-up or had large drop-outs with few remaining patients at or beyond 1 year. We also reviewed the abstract by Tarp et al .3 Among a total of 4831 subjects, 1944 were specifically analysed for …

Dr. Roubille, et al reply

To the Editor: We thank Castaneda, et al 1 for their comments on our article2. We do support comorbidity management in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and psoriasis (PsO) in daily practice to ensure optimal care and outcomes, and completely agree with the recently published Spanish recommendations3. Given that patients with RA have increased risk of cardiovascular (CV) morbidity and mortality4, CV monitoring appears critical. In the CARMA (CARdiovascular in rheuMAtology) study, Castaneda, et al 5 reported that patients with RA, PsA, and PsO had higher prevalence of CV events while receiving biological therapy despite being in low disease activity for almost half of the patients. Notably, almost half of the patients also received nonsteroidal antiinflammatory drugs and/or glucocorticoids (patients with RA), which may have increased CV risk6. Regardless of the other confounding factors, these data reinforce the importance of CV monitoring and … Address correspondence to Dr. C. Roubille, University of Montreal Hospital Research Center (CRCHUM), Notre-Dame Hospital, Montreal, Quebec H2L 1S6, Canada. E-mail: camille.roubille{at}gmail.com

THU0412 Cardiovascular Outcomes in Patients with Rheumatoid Arthritis, Psoriasis and Psoriatic Arthritis: A Systematic Review and Meta-Analyses

Background Rheumatoid arthritis (RA), psoriasis (PsO) and psoriatic arthritis (PsA) are associated with increased risk of CV-mortality but less clearly related to specific cardiovascular outcomes (CVO.) Objectives To evaluate important CVO in RA, PsO and PsA patients. Methods Medline, Embase, Cochrane and abstracts from ACR/EULAR/AAD/EADV were searched for in English language full-length articles and abstracts published up to January 15, 2013 describing CVO in observational studies in RA, PsO and PsA patients. Outcomes included all-cause and CV-mortality, and specific CVO including myocardial infarction (MI)/acute coronary syndrome (ACS), cerebrovascular accident (CVA – including stroke or transient ischemic attack), heart failure (HF) and peripheral artery disease (PAD). Random effects meta-analyses were performed. Results Out of 3457 references, 127 observational studies (RA=89; PsO=27; PsA=11) were included. Important effect size estimates represented as standardized mortality (SMR) and morbidity (SMoR) ratios are listed in Table 1. Table 1. Effect size estimates for important cardiovascular outcomes CVO RA PsO PsA Fatal CVO SMR SMR SMR  All-cause mortality 1.59 (1.47–1.71) 1.43 (1.14–1.81) 1.46 (1.03–2.07)  CV-mortality 1.58 (1.47–1.70) 1.32 (1.12–1.57) 1.61 (1.09–2.38) Specific CVO SMoR SMoR SMoR  MI/ACS 1.85 (1.55–2.22) 1.23 (1.07–1.42) 1.55 (0.57–4.21)  CVA 1.56 (1.26–1.94) 1.18 (1.06–1.32) 0.91 (0.34–2.43)  PAD 1.95 (1.05–3.63) 1.31 (1.17–1.45) 1.53 (1.20–1.94)  HF 1.54 (1.29–1.83) 1.35 (1.13–1.63) 1.43(1.08–1.90) Conclusions RA, PsO and PsA are associated with several important CVOs including less reported outcomes such as PAD, CVA and HF. These complications may be less recognized by physicians. Fewer studies exist for PsA but CVOs appear increased overall. Risk reduction strategies should be considered. Acknowledgements Dr. Ben Vandermeer provided invaluable statistical consulation and analysis. Disclosure of Interest : A. McFarlane Grant/research support: This study was supported by an unrestricted grant from AbbVie., C. Roubille Grant/research support: This study was supported by an unrestricted grant from AbbVie. Fellowship grants/bursary from the Foundation of the University of Montreal Hospital Center (CHUM)., V. Richer Grant/research support: This study was supported by an unrestricted grant from AbbVie., T. Starnino Grant/research support: This study was supported by an unrestricted grant from AbbVie., C. McCourt Grant/research support: This study was supported by an unrestricted grant from AbbVie. Salary for the fellowship in Vancouver was funded by a Fellowship from Janssen-Ortho Canada and the British Association of Dermatology., P. Fleming Grant/research support: This study was supported by an unrestricted grant from AbbVie., S. Siu Grant/research support: This study was supported by an unrestricted grant from AbbVie., J. Kraft Grant/research support: This study was supported by an unrestricted grant from AbbVie. Investigator support from Abbvie, Amgen, Galderma, Janssen, Novartis., Consultant for: Abbvie, Amgen, Galderma, Janssen, Novartis, Leo., Speakers bureau: Abbvie, Amgen, Galderma, Janssen, Leo., C. Lynde Grant/research support: This study was supported by an unrestricted grant from AbbVie. Investigator support: Abbvie, Amgen, Celgene, Janssen-Ortho, Novartis, Eli Lilly, Merck, Leo Pharma., Consultant for: Abbvie, Amgen, Celgene, Janssen-Ortho, Novartis, Eli Lilly, Merck, Leo Pharma., Speakers bureau: Abbvie, Amgen, Celgene, Janssen-Ortho, Novartis, Eli Lilly, Merck, Leo Pharma., J. Pope Grant/research support: This study was supported by an unrestricted grant from AbbVie. Research support from AbbVie, Actelion, Amgen, Astra Zeneca, Bayer, BMS, Celgene, Genentech, GSK, BMS, Jansen & Jansen, MedImmune, Mediquest, Novartis, Pfizer, Roche, United Chemicals Belgium., Consultant for: AbbVie, Actelion, Amgen, Astra Zeneca, Bayer, BMS, Celgene, Genentech, GSK, BMS, Jansen & Jansen, MedImmune, Mediquest, Novartis, Pfizer, Roche, United Chemicals Belgium., W. Gulliver Grant/research support: This study was supported by an unrestricted grant from AbbVie. Research support from Abbott/AbbVie, Actelion, Amgen, Astellas, Bio-K, Celgene, Galderma, Janssen, LEO Pharma, Merck/Schering, Novartis, Pfizer, Roche and Valeant., Consultant for: Abbott/AbbVie, Actelion, Amgen, Astellas, Bio-K, Celgene, Galderma, Janssen, LEO Pharma, Merck/Schering, Novartis, Pfizer, Roche and Valeant., Speakers bureau: Abbott/AbbVie, Actelion, Amgen, Astellas, Bio-K, Celgene, Galderma, Janssen, LEO Pharma, Merck/Schering, Novartis, Pfizer, Roche and Valeant., J. Dutz Grant/research support: This study was supported by an unrestricted grant from AbbVie. Research support Abbvie, Centocor, Janssen- Ortho, Novartis, ONO Pharmaceuticals, Roche, Consultant for: Janssen-Ortho, AbbVie Amgen, Leo, Roche, Speakers bureau: Janssen-Ortho, AbbVie Amgen, Leo, L. Bessette Grant/research support: This study was supported by an unrestricted grant from AbbVie. Research support AbbVie, UCB, Janssen, and Amgen., Consultant for: AbbVie, UCB, Janssen, and Amgen., Speakers bureau: AbbVie, UCB, Janssen, and Amgen., R. Bissonnette Grant/research support: This study was supported by an unrestricted grant from AbbVie. Research grants and honoraria AbbVie, Amgen, Celgene, Eli-Lilly Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Tribute., Consultant for: AbbVie, Amgen, Celgene, Eli-Lilly Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Tribute., B. Haraoui Grant/research support: This study was supported by an unrestricted grant from AbbVie. Grant support from Abbvie, Amgen, BMS, Celgene, Janssen, Pfizer, Roche, UCB., Consultant for: Abbvie, Amgen, BMS, Celgene, Janssen, Pfizer, Roche, UCB., S. Keeling Grant/research support: This study was supported by an unrestricted grant from AbbVie. Unrestricted educational funding received from the following:Pfizer, Janssen, Astrazeneca, Roche., Consultant for: Participated in advisory boards as consultant for:Janssen, AbbVie, Roche, Amgen. DOI 10.1136/annrheumdis-2014-eular.1348

OP0277 Effect of Disease Modifying Drugs on Bone Mineral Density in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, Psoriasis, and Ankylosing Spondylitis: A Meta-Analysis

Background Inflammatory arthritis is a risk factor for osteoporosis and it may be that treating systemic inflammation can improve bone mineral density (BMD). Objectives The aim of this study was to examine if DMARDs, steroids, and biologic therapies for rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PSO), and ankylosing spondylitis (AS) affect BMD. The aim of this study was to examine if DMARDs, steroids, and biologics for rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PSO), and ankylosing spondylitis (AS) affect BMD. Methods Medline, Embase, and Cochrane were searched from 1960 to present using English randomised controlled trials in adults. Review articles were excluded. Studies were grouped based on disease, treatment type, and site of BMD measurement (wrist, lumbar spine (LS), hip). ΔBMD were reported as standardized mean difference. Results 393 studies were identified; 13 were eligible (11 RA, 0 PsA, 0 PSO, 2 AS). For RA, significantly less wrist bone loss was seen with biologics (ΔBMD =0.27SD, 95% CI 0.07-0.47, P=0.009, I2=0%) and corticosteroids (ΔBMD =0.54SD, 95% CI 0.23-0.85, P=0<0.001, I2=0%). Biologics had no significant effect on LS and hip BMD. Corticosteroids had more bone loss compared to placebo on LS (ΔBMD = -0.25SD, 95% CI -0.42 to -0.08, P=0.003, I2=52%) but no difference for hip. For AS, significant BMD increase was seen with biologics in both LS (ΔBMD = 0.98SD, 95% CI 0.73-1.23, P<0.001, I2=16%) and hip (ΔBMD = 0.38SD, 95% CI 0.14-0.63, P=0.002, I2=0%). PsA and PSO could not be analyzed due to no suitable RCTs. Conclusions Based on our RA analysis, biologics and steroids were associated with less wrist bone loss (where synovitis is often present) but had no effect on BMD at the hip. Corticosteroids were associated with more bone loss in LS whereas biologics had no effect on BMD at the LS. For AS, biologics were associated with increase in both LS and hip BMD. Disclosure of Interest S. Siu Grant/research support: This study was supported by an unrestricted grant from AbbVie. B. Haraoui Grant/research support: This study was supported by an unrestricted grant from AbbVie. Other grant support from Abbvie, Amgen, BMS, Celgene, Janssen, Pfizer, Roche, UCB. Consultant for: Abbvie, Amgen, BMS, Celgene, Janssen, Pfizer, Roche, UCB. C. Roubille Grant/research support: This study was supported by an unrestricted grant from AbbVie. Fellowship grants/bursary from the Foundation of the University of Montreal Hospital Center (CHUM). V. Richer Grant/research support: This study was supported by an unrestricted grant from AbbVie. T. Starnino Grant/research support: This study was supported by an unrestricted grant from AbbVie. C. McCourt Grant/research support: This study was supported by an unrestricted grant from AbbVie. Salary for the fellowship in Vancouver was funded by a Fellowship from Janssen-Ortho Canada and the British Association of Dermatology. A. McFarlane Grant/research support: This study was supported by an unrestricted grant from AbbVie. P. Fleming Grant/research support: This study was supported by an unrestricted grant from AbbVie. J. Kraft Grant/research support: This study was supported by an unrestricted grant from AbbVie. Investigator support from Abbvie, Amgen, Galderma, Janssen, Novartis. Consultant for: Abbvie, Amgen, Galderma, Janssen, Novartis, Leo. Speakers bureau: Abbvie, Amgen, Galderma, Janssen, Leo. C. Lynde Grant/research support: This study was supported by an unrestricted grant from AbbVie. Investigator support: Abbvie, Amgen, Celgene, Janssen-Ortho, Novartis, Eli Lilly, Merck, Leo Pharma. Consultant for: Abbvie, Amgen, Celgene, Janssen-Ortho, Novartis, Eli Lilly, Merck, Leo Pharma. Speakers bureau: Abbvie, Amgen, Celgene, Janssen-Ortho, Novartis, Eli Lilly, Merck, Leo Pharma. W. Gulliver Grant/research support: This study was supported by an unrestricted grant from AbbVie. Abbott/AbbVie, Actelion, Amgen, Astellas, Bio-K, Celgene, Galderma, Janssen, LEO Pharma, Merck/Schering, Novartis, Pfizer, Roche and Valeant. Consultant for: Abbott/AbbVie, Actelion, Amgen, Astellas, Bio-K, Celgene, Galderma, Janssen, LEO Pharma, Merck/Schering, Novartis, Pfizer, Roche and Valeant. Speakers bureau: Abbott/AbbVie, Actelion, Amgen, Astellas, Bio-K, Celgene, Galderma, Janssen, LEO Pharma, Merck/Schering, Novartis, Pfizer, Roche and Valeant. S. Keeling Grant/research support: This study was supported by an unrestricted grant from AbbVie. Unrestricted educational funding received from the following:Pfizer, Janssen, Astrazeneca, Roche; Participated in advisory boards as consultant for:Janssen, AbbVie, Roche, Amgen. J. Dutz Grant/research support: This study was supported by an unrestricted grant from AbbVie. Other research support Abbvie, Centocor, Janssen- Ortho, Novartis, ONO Pharmaceuticals, Roche. Consultant for: Janssen–Ortho, AbbVie Amgen, Leo, Roche. Speakers bureau: Janssen-Ortho, AbbVie Amgen, Leo. L. Bessette Grant/research support: This study was supported by an unrestricted grant from AbbVie. Other research support AbbVie, UCB, Janssen, and Amgen. Consultant for: AbbVie, UCB, Janssen, and Amgen. Speakers bureau: AbbVie, UCB, Janssen, and Amgen. R. Bissonnette Grant/research support: This study was supported by an unrestricted grant from AbbVie. Resdearch grnats and honoraria AbbVie, Amgen, Celgene, Eli-Lilly Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Tribute. Consultant for: AbbVie, Amgen, Celgene, Eli-Lilly Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Tribute. J. Pope Grant/research support: This study was supported by an unrestricted grant from AbbVie. AbbVie, Actelion, Amgen, Astra Zeneca, Bayer, BMS, Celgene, Genentech, GSK, BMS, Jansen & Jansen, MedImmune, Mediquest, Novartis, Pfizer, Roche, United Chemicals Belgium, Consultant for: AbbVie, Actelion, Amgen, Astra Zeneca, Bayer, BMS, Celgene, Genentech, GSK, BMS, Jansen & Jansen, MedImmune, Mediquest, Novartis, Pfizer, Roche, United Chemicals Belgium DOI 10.1136/annrheumdis-2014-eular.2540