Patrick Fleming

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.

The Relationship of Obesity With the Severity of Psoriasis A Systematic Review

Background: Psoriasis is a chronic inflammatory disease associated with obesity. The increased production of adipocytokines in central adiposity contributes to the systemic inflammation of obesity and perhaps to psoriasis. Objective: The objective of this systematic review is to determine the association of obesity with psoriasis severity. Methods: We searched PubMed, EMBASE, and Cochrane Database for English-language papers involving human subjects for all years. We extracted data on age, sex, body mass index (BMI), proportion obese, and psoriasis severity index score (PASI). Results: We identified 254 articles in our search and included 9. The sample size was 134 823 psoriasis patients. Seven of the 9 studies found a statistically significant association of increased psoriasis severity with higher BMI. Conclusion: Increased severity of psoriasis appears to be associated with increased BMI. Most studies were cross-sectional or case-control, making it difficult to determine temporality. Dermatologists should consider recording BMI for psoriasis patients and offering them lifestyle counseling.

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.

The prevalence of anxiety in patients with psoriasis: a systematic review of observational studies and clinical trials

Psoriasis and anxiety are chronic conditions with significant morbidity and there is evidence that they may exacerbate one another. There is little data on the prevalence of anxiety in psoriasis and the effect of psoriasis treatment on comorbid anxiety. The objective of this study was to perform a systematic review of the literature to describe the prevalence and severity of clinical anxiety disorders or anxiety symptoms among adult patients with psoriasis and characterize the effect of anti‐psoriatic interventions on clinical anxiety disorders or anxiety symptoms. We searched PubMed, EMBASE, and the Cochrane Database using search terms ‘psoriasis’ and ‘anxiety’. Results were tabulated and verified by two independent reviewers. Meta‐analyses were not performed due to heterogeneity of data. Of 213 publications identified, 938 194 patients from 15 papers were included. The mean age ranged from 31.9–59.4 years old, with a mean PASI score of 7.65–22.8 (reported by nine studies) and a body surface area involvement of 25.9–39.8% (reported by two studies). The prevalence of anxiety in patients with psoriasis was 7–48%, which was significantly higher than healthy controls in two of three studies (HR 1.29–1.31, P = 0.001 and OR 2.91 [95% CI, 2.01–4.21], P < 0.001). Four of five studies (n = 2029) demonstrated an improvement in anxiety symptoms with psoriasis treatment. This review demonstrates a high prevalence of anxiety of adult patients with psoriasis suggesting that patients would benefit from systematic screening. Although the data suggest that anxiety may be improved through various psoriasis treatments, larger prospective randomized trials are needed to confirm this effect.

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.

Risk of infection in patients with atopic dermatitis treated with dupilumab: A meta-analysis of randomized controlled trials

Background: Atopic dermatitis (AD) is characterized by skin barrier defects, T helper type 2 cell activation, and increased risk for cutaneous and extracutaneous infections. In clinical trials, dupilumab appeared to decrease rates of skin infections in AD. Objective: We aimed to determine the impact of dupilumab on rates of skin and other infections in patients with moderate‐to‐severe AD. Methods: We conducted a systematic review and meta‐analysis of randomized controlled trials of dupilumab for AD. We searched the PubMed database for relevant studies. Risk ratios (RRs) and 95% confidence intervals (CIs) for skin infections, herpesvirus infections, and overall infections and infestations were calculated for dupilumab compared with for placebo by using binary random effects meta‐analysis. For the analysis of eczema herpeticum, Peto odds ratios were calculated. Results: Eight randomized controlled trials in 4 publications with 2706 participants were included, with follow‐up time ranging from 4 to 52 weeks. Meta‐analysis including all dosing schedules and follow‐up times showed a RR of skin infection of 0.54 (95% CI, 0.42‐0.70) and an odds ratio of eczema herpeticum of 0.34 (95% CI, 0.14‐0.84) for dupilumab compared with placebo. No significant association was found for dupilumab with overall herpesvirus infections (RR, 1.16; 95% CI, 0.78‐1.74) and overall infections (RR, 0.98; 95% CI, 0.83‐1.16). Limitations: Our analysis is limited by the short follow‐up time in most trials and the relatively low number of patients treated with dupilumab to date. Conclusions: Dupilumab is associated with a decreased incidence of skin infections and eczema herpeticum in adults with moderate‐to‐severe AD. The mechanism underlying this association is uncertain but is likely related to improvement in AD severity. Dupilumab, a monoclonal antibody targeting interleukin 4 and interleukin 13, appears to significantly decrease the risk for skin infections and eczema herpeticum in adults with moderate‐to‐severe AD.

Psoriasis and Adverse Pregnancy Outcomes: A Systematic Review of Observational Studies

Psoriasis is a chronic inflammatory disorder with significant physical and psychological sequelae. The majority of individuals experience disease onset in early adult life – for women this often occurs during their reproductive years. While some autoimmune diseases have been shown to affect pregnancy outcomes adversely, such a relationship has not been well studied in psoriasis. We searched PubMed, Embase and the Cochrane database for published articles examining psoriasis and adverse pregnancy outcomes, and included observational studies and clinical trials evaluating direct measures of maternal and fetal morbidity and mortality. Four of the nine included articles reported a statistically significant increase in the risk of at least one outcome, including spontaneous abortion, caesarean delivery, low birth weight, macrosomia, large‐for‐gestational age, and a composite outcome consisting of both prematurity and low birth weight. However, these associations were not always consistent across studies. Overall, there was no clear evidence of increased adverse outcomes in pregnant women with psoriasis.

Do Biologics Protect Patients With Psoriasis From Myocardial Infarction? A Retrospective Cohort

Background: Psoriasis is a chronic immune-mediated inflammatory disorder that affects approximately 2% to 3% of the population, which translates to 17 million in North America and Europe and approximately 170 million people worldwide. Although psoriasis can occur at any age, most cases develop before age 40 years. Some larger studies have noted bimodal age at onset with the first peak occurring at approximately age 30 years and the second peak at around 55 to 60 years, but most patients have a younger age of onset (15-30 years). Psoriasis is associated with multiple comorbidities, decreased quality of life, and decreased longevity of life. Two recent systematic reviews and a meta-analysis concluded that psoriasis patients are at increased risk of major adverse cardiovascular events. Multiple studies confirm that many of the comorbidities found in patients with psoriasis are also important risk factors for cardiovascular disease, stroke, diabetes mellitus, hypertension, hyperlipidemia, obesity, and metabolic syndrome. Methods: We conducted a retrospective cohort study using charts from a dermatology clinic combined with an administrative database of patients with moderate to severe psoriasis in Newfoundland and Labrador, Canada. We examined the role of clinical predictors (age of onset of psoriasis, age, sex, biologic use) in predicting incident myocardial infarction (MI). Results: Logistic regression revealed that age of onset (odds ratio [OR], 8.85; P = .005), advancing age (OR, 1.07; P < .0001), and being male (OR, 3.64; P = .018) were significant risk factors for the development of MI. Neither biologic therapy nor duration of biologic therapy were statistically significant risk factors for the development of MI. Our study found that in patients with psoriasis treated with biologics, there was a nonsignificant trend in reduced MI by 78% (relative risk, 0.18; 95% confidence interval, 0.24-1.34; P = .056). Conclusion: Our study demonstrated a trend toward decreased MI in patients with moderate to severe psoriasis on biologics. Patients with an early age of onset of psoriasis (<25 years) were nearly 9 times more likely to have an MI. Clinicians should consider appropriate cardiovascular risk reduction strategies in patients with psoriasis.