RA is associated with early ischaemic heart disease. This appears to be driven largely by the presence of chronic inflammation. Studies suggest that treatment with disease-modifying drugs such as MTX ...may reduce the incidence of cardiovascular events in RA. Anti-TNF therapies significantly reduce inflammation in RA. However, the extent to which these agents also reduce cardiovascular disease (CVD) is uncertain. The purpose of this study was to explore the effect of anti-TNF agents on CVD in RA using a systematic literature review.
We searched for studies of adults with RA treated with TNF antagonists where cardiovascular outcomes were recorded using MEDLINE, EMBASE, Cochrane Database, Database of Abstracts and Reviews of Effects, Health Technology Appraisal, Science Citation Index and Clinical Evidence from 1989 to 2010. Conference proceedings for the British Society of Rheumatology, ACR and EULAR between 2005 and 2009 were hand searched. Two reviewers assessed abstracts for inclusion and then quality of selected papers was assessed.
A total of 1840 abstracts were identified and 20 articles were suitable for inclusion. Information was obtained on the effect of TNF antagonists on overall CVD events, myocardial infarction, strokes and heart failure.
In many studies, TNF antagonists appear to reduce the likelihood of CVD in individuals with RA. Reassuringly, there does not appear to be an increased risk of cardiac failure. However, the reduction in CVD is not as consistently seen as with studies of MTX.
Objective
To assess the long-term safety, tolerability, and effectiveness of tocilizumab (TCZ) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs ...(csDMARDs) in clinical practice in patients with moderate to severe rheumatoid arthritis (RA).
Methods
Patients in the 24-week, open-label ACT-SURE study who had at least a moderate EULAR response by week 24 and were from a participating country were eligible for this long-term extension (LTE); the patients continued to receive TCZ 8 mg/kg intravenously every 4 weeks as monotherapy or in combination with ≥ 1 csDMARD for up to an additional 108 weeks. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs). Effectiveness endpoints included Disease Activity Score in 28 joints (DAS28) responses, American College of Rheumatology (ACR) responses, and patient-reported outcomes (PROs).
Results
Of the 1102 patients who completed the core 24-week study, 934 participated in the LTE; the median exposure to TCZ was 64.3 weeks. From baseline to the end of the LTE, AEs and SAEs occurred in 90% and 9% of patients, respectively. The overall event rates (95% CI) of AEs and SAEs were 406.5 per 100 patient-years (PY) (395.5, 417.8) and 8.8 per 100 PY (7.3, 10.6), respectively. Mean (SD) improvement in DAS28 was 4.12 (1.18),
P
< 0.0001. The DAS28 remission rates, ACR response rates, and PRO scores were maintained during the LTE study.
Conclusion
In clinical practice, TCZ as monotherapy or in combination with csDMARDs was safe, well tolerated, and efficacious in patients with moderate to severe RA.
Background
Rheumatoid arthritis is a systemic inflammatory condition associated with increased cardiovascular risk that may be due to underlying endothelial dysfunction and subsequent aortic ...stiffening. We hypothesized that supplementation with tetrahydrobiopterin (BH4) would recouple endothelial nitric oxide synthase and thus improve endothelial function and consequently reduce aortic stiffness.
Methods and Results
We conducted 2 randomized, double‐blinded, placebo‐controlled crossover studies examining 2 separate regimens: an acute regimen, with a single dose of BH4 400 mg versus placebo (n=18), and a short‐term regimen, composed of a 1‐week treatment with BH4 400 mg once daily versus placebo (n=15). Flow‐mediated dilatation and aortic pulse wave velocity were studied 4 times, before and after each treatment phase. Acute BH4 supplementation led to an improvement of flow‐mediated dilatation, whereas placebo had no effect (mean±SD of effect difference 2.56±4.79%; P=0.03). Similarly, 1‐week treatment with BH4 improved endothelial function, but there was no change with placebo (mean±SD of effect difference 3.50±5.05%; P=0.02). There was no change in aortic pulse wave velocity following acute or short‐term BH4 supplementation or placebo (mean±SD of effect difference: acute 0.09±0.67 m/s, P=0.6; short‐term 0.03±1.46 m/s, P=0.9).
Conclusion
Both acute and short‐term supplementation with oral BH4 improved endothelial function but not aortic stiffness. This result suggests that BH4 supplementation may be beneficial for patients with rheumatoid arthritis by improving endothelial dysfunction and potentially reducing risk of cardiovascular disease. There appears to be no causal relationship between endothelial function and aortic stiffness, suggesting that they occur in parallel, although they may share common risk factors such as inflammation.
Over the last decade vitamin D (Vit D) has been the focus of considerable interest as a potential immunomodulator in a variety of conditions including autoimmune disease. Its influence in juvenile ...idiopathic arthritis (JIA) however is unclear. We therefore wished to clarify a possible link with the currently available evidence. A systematic literature review was undertaken using Embase, Cochrane and Medline for manuscripts up to May 2011. Search results were then assessed by two independent reviewers and relevant articles were further screened by full text review. Only those specifically reporting Vit D levels or its supplementation in JIA (ages between 0 and 18 years) were selected. Meta-analysis was performed where possible with those papers reporting similar data and analysis techniques. In total, 19 papers (
n
= 745) were included in the review. Fourteen papers quoted 25(OH)D levels within their study groups with a mean of 24.56 ng/ml (range, 11.5–56.4 ng/ml) in a total of 529 children. Eleven papers quoted 1,25(OH)
2
D levels with a mean of 31.09 pg/ml (range 6.1–65.0 pg/mol) in a total of 518 children. Three studies reporting the prevalence of Vit D deficiency in their cohorts found that up to 82 % of children had insufficient levels. Five papers reported Vit D levels by JIA subtype and showed lower levels of both 25(OH)D mean 15.35, range 8.5–24.5 ng/ml and 1,25(OH)
2
D mean 22.89, range 5.6–50 pg/ml in systemic JIA. Four papers reported Vit D supplementation in JIA however the treatment effect was unclear. At present no clear evidence exists to support a link between Vit D level and JIA. Furthermore, the role of Vit D supplementation in the management of JIA is lacking. Despite Vit D levels appearing to be lower in JIA, interpretation is problematic as no agreed definition of Vit D deficiency exists in this population. A need remains therefore to standardise Vit D levels in the paediatric population and in JIA.
In England and Wales, the National Institute for Health and Clinical Excellence (NICE) has provided guidance technology appraisals (TAs) 130, 186, 195, 198 and 225 on the use of biologic drugs for ...the treatment of RA. This is based on an analysis of efficacy, safety and cost-effectiveness, and has resulted in a complex management pathway that restricts freedom to prescribe biologics according to their licensed indications. Specifically, TNF antagonists are the only class of biologics that can be used first line in DMARD-inadequate responders, and only in patients with a persistent 28-joint DAS score of 5.1. Alternative biologic agents are denied to those with contraindications to anti-TNF drugs and are also not supported following intolerance to TNF antagonists. Rituximab is the only class of biologic permitted after TNF antagonist inefficacy, in the absence of a contraindication to its use, whereas abatacept and tocilizumab are licensed and may be a more efficacious choice at this stage in some patient groups. Furthermore, for patients who demonstrate sequential inadequate responses, treatment is restricted to one TNF antagonist, rituximab and tocilizumab, whereas abatacept is only a permitted choice when rituximab is contraindicated or has been withdrawn because of an adverse event. In this review, we discuss the treatment algorithm published by NICE, and suggest alternatives where perceived deficiencies exist.
Biologic agents have become indispensable in the management of autoimmune disease particularly rheumatological conditions. The lives of countless individuals have been improved following treatment ...with these drugs. Unfortunately, their cost prohibits more widespread use around the globe. This critical issue has been addressed by the introduction of biosimilars into the market. These therapies have been developed to resemble the originator molecule as closely as possible and to increase competition in the therapy area thus allowing costs to be reduced. Our review is intended to offer an update on biosimilars including logistic considerations on their introduction into routine practice.
Limited evidence exists regarding the validity of clinical examination for the detection of shoulder pathology. We therefore wished to establish the sensitivity, specificity, positive predictive ...value and negative predictive value of clinical tests and magnetic resonance imaging (MRI) in the diagnosis of rotator cuff disorders against findings at arthroscopy. Using recognised tests for specific shoulder lesions, 117 patients with shoulder symptoms awaiting surgery were examined in a standard manner. The diagnoses were categorised and compared with abnormalities found on MRI and at surgery. Results were cross-tabulated to determine the above parameters. Ninety-four patients formed the study group with a mean age of 51 years. The median duration of symptoms was 45 weeks. For clinical examination, sensitivity and specificity to detect a tear or rupture of supraspinatus were 30 % (16/54) and 38 % (15/40) and, for the detection of any pathology, were 94 % (67/71) and 22 % (5/23), respectively, compared with arthroscopy. Correspondingly, the sensitivity of MRI compared with arthroscopy to detect a tear or rupture of supraspinatus was 90 % (28/31) with a specificity of 70 % (46/53), whereas for the detection of any abnormality, the sensitivity was 92 % (65/71) with a specificity of 48 % (11/23). The sensitivity of detecting any rotator cuff abnormality is high when examination and MRI is compared with arthroscopy with the specificity being greater with MRI than examination. In patients with shoulder symptoms severe enough to consider surgery, clinical assessment followed by specific imaging may help define the pathology in order to direct appropriate management.
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