Impact of rheumatoid arthritis on work capacity impairment and its predictors

Clinical Rheumatology - A decline in work capacity is an important outcome of rheumatoid arthritis (RA). In a first such study from India, we evaluated the impact of RA on work capacity and its...     

Angiotensin-Receptor Blockade Improves Inflammation and Endothelial Dysfunction in Ankylosing Spondylitis: ARB-AS Study

Cardiovascular (CV) disease is the leading cause of premature death in ankylosing spondylitis (AS). Atherosclerosis and AS share similar pathogenic mechanisms. The proven benefits of angiotensin-receptor blockers (ARBs) in atherosclerotic cardiovascular disease and their role in immune mediation provide strong rationale to investigate its impact with olmesartan on inflammation and endothelial dysfunction in AS. To investigate the effect of olmesartan on inflammation and endothelial dysfunction in AS. 40 AS patients were randomized to receive 24 weeks of treatment with olmesartan (10 mg/day, n  = 20) and placebo ( n  = 20) as an adjunct to existing stable antirheumatic drugs. Markers of endothelial function included the following: flow-mediated dilation (FMD) assessed by AngioDefender, endothelial progenitor cells (EPCs) estimated by flow cytometry, nitrite (nitric oxide surrogate), intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and inflammatory measures including Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAS) and bath ankylosing spondylitis functional index (BASFI); erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); proinflammatory cytokines (interleukin-1 [IL-1], IL-6, tumor necrosis factor-α [TNF-α]) and marker of oxidative stress– thiobarbituric acid reactive substances (TBARS) estimated at baseline and after treatment. Health assessment questionnaire disability index (HAQDI), 36-item short form survey (SF-36), and systematic coronary risk evaluation (SCORE) were estimated using standard tools. FMD improved significantly in the olmesartan group (5.83 ± 0.31% to 7.68 ± 0.27%, p  ≤  0.05) as compared with placebo (5.89 ± 0.35% to 6.04 ± 0.32%, p  = 0.33). EPC population, nitrite, VCAM-1, and TBARS levels improved significantly in olmesartan group as compared with placebo ( p ≤ 0.05). Olmesartan significantly decreased ASDAS, BASDAI, BASFI, ESR, CRP, IL-6, TNF-α, and SCORE as compared with placebo. HAQDI and SF-36 (PH) scores improved significantly in olmesartan group as compared with placebo. Olmesartan reduces inflammatory disease activity, improves quality of life (QOL), and decreases CV risk demonstrating the immunomodulatory, vasculoprotective, and cardioprotective potential of this drug in AS.     

Cost-effective analysis of disease-modifying anti-rheumatic drugs in rheumatoid arthritis

The main objective of the study was to perform the pharmacoeconomic analysis of synthetic disease-modifying anti-rheumatic drugs in rheumatoid arthritis patients. A prospective, observational study was conducted in 98 rheumatoid arthritis (RA) patients meeting 2010 Rheumatoid Arthritis Classification Criteria. Treatment-naive RA patients were initiated on synthetic disease-modifying anti-rheumatic drugs (DMARD/s) and followed up for 3 months. Average cost-effectiveness analysis was done by taking Health Assessment Questionnaire Disability Index (HAQ-DI) score as a measure of effectiveness. Out of the 98 RA patients, 15.30% were males and 84.69% females. 80.61% RA patients are seropositive. Majority of the study population patients (55%) were on combination of three synthetic DMARDs and almost a quarter (24.48%) were on combination of two synthetic DMARDs. The mean value of DAS 28 at baseline was 6.07 ± 1.33 and after 3 months treatment, the mean was 3.84 ± 1.11. The mean disability index measured by HAQ-DI was significantly reduced from 1.43 ± 0.71 to 0.81 ± 0.61, p < 0.001, after 3 months treatment. The direct medical cost of treatment of RA per month is 997.05 rupees. The average cost-effectiveness ratio of combination of synthetic DMARDs was 1533.92 rupees. Treatment of RA with synthetic DMARDs controls disease activity and improves disability with reasonable cost of treatment. The majority of the direct medical cost is attributable to cost of medicine and laboratory investigation. Use of quality generic drugs and an early diagnosis would minimize the economic burden on the patient.     

Autonomic dysfunction in psoriatic arthritis

Autonomic nervous system (ANS) involvement has been studied in systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, Sjogren’s syndrome, and ankylosing spondylitis but still has not been studied in psoriatic arthritis (PsA). The aim of this study was to investigate the prevalence and the nature of autonomic neuropathy in patients with PsA. Sixteen patients of PsA and 15 age and sex matched control subjects were studied prospectively using a battery of noninvasive tests. Cardiovascular autonomic neuropathy (CAN) was diagnosed by applying four cardiovascular reflex tests, and peripheral sympathetic autonomic function was assessed by Sudoscan. Patients with PsA had significantly higher heart rate response to standing (p?=?0.01), blood pressure response to standing (p?=?0.02), and Sudoscan (p?=?0.01) when compared with healthy controls. Fifty percent (n?=?8) of the patients with PsA had at least two or more abnormal CAN parasympathetic dysfunction; of these, 18.75 % (n?=?3) of the patients had abnormal parasympathetic and sympathetic dysfunction, 68.7 % (n?=?11) and 25 % (n?=?4) of the patients had at least one abnormal parasympathetic and sympathetic parameters, respectively, and 37.5 % (n?=?6) of the patients had moderate sudomotor dysfunction. About 18.7 % (n?=?3) of our parasympathetic dysfunction patients had autonomic symptoms. None of healthy volunteers had abnormal ANS dysfunction. Heart rate response significantly correlated with erythrocyte sedimentation rate (p?<?0.05) and C-reactive protein (p?<?0.05) levels. In conclusion, cardiovascular autonomic and peripheral sympathetic neuropathy occurs in PsA. Parasympathetic function is more commonly found to be abnormal than sympathetic function. There is no correlation of peripheral sympathetic dysfunction with cardiovascular autonomic neuropathy.     

Advanced glycation end-products inhibition improves endothelial dysfunction in rheumatoid arthritis

Aim: Chronic inflammation in rheumatoid arthritis is associated with vascular endothelial dysfunction. The objective was to study the efficacy and safety of advanced glycation end products (AGEs) inhibitor (benfotiamine 50 mg + pyridoxamine 50 mg + methylcobalamin 500 μg, Vonder^® (ACME Lifescience, Baddi, Himachal Pradesh, India)) on endothelial function in rheumatoid arthritis (RA). Methods: Twenty‐four patients with established active RA with high disease activity (Disease Activity Score of 28 joints [DAS28 score] > 5.1) despite treatment with stable doses of conventional disease‐modifying antirheumatic drugs were investigated. Inflammatory disease activity (DAS28 and Health Assessment Questionnaire‐Disability Index [HAQ‐DI] scores, erythrocyte sedimentation rate [ESR] and C‐reactive protein [CRP]), markers of endothelial dysfunction, serum nitrite concentration and endothelium‐dependent and ‐independent vasodilation of the brachial artery were measured before and after 12 weeks therapy with twice a day oral AGEs inhibitor. Results: After treatment, flow‐mediated vasodilation improved from 9.64 ± 0.65% to 15.82 ± 1.02% (P < 0.01), whereas there was no significant change in endothelium‐independent vasodilation with nitroglycerin and baseline diameter; serum nitrite concentration significantly reduced from 5.6 ± 0.13 to 5.1 ± 0.14 μmol/L (P = 0.004), ESR from 63.00 ± 3.5 to 28.08 ± 1.5 mm in the first h (P < 0.01) and CRP levels from 16.7 ± 4.1 to 10.74 ± 2.9 mg/dL (P < 0.01). DAS28 and HAQ‐DI scores were significantly reduced, from 5.9 ± 0.17 to 3.9 ± 0.17 (P < 0.01) and 4.6 ± 0.17 to 1.7 ± 0.22 (P < 0.01), respectively. Conclusions: Advanced glycation end products inhibitor improves endothelial dysfunction and inflammatory disease activity in RA. In RA, endothelial dysfunction is part of the disease process and is mediated by AGEs‐induced inflammation.     

Therapeutic effects of spironolactone on a collagen-induced arthritis model of rheumatoid arthritis

Background

Rheumatoid arthritis (RA) is an autoimmune disease characterized by increased inflammation of synovial joint. The collagen-induced arthritis (CIA) is a widely used animal model for RA. Spironolactone possesses potent anti-inflammatory and immune modifying properties that might make it an excellent medical intervention for rheumatic diseases.

Minocycline improves peripheral and autonomic neuropathy in type 2 diabetes: MIND study

Diabetic peripheral neuropathy and diabetic autonomic neuropathy are serious and common complications of diabetes associated with increased risk of mortality and cardiovascular disease. We sought to evaluate the safety and efficacy of minocycline in type 2 diabetic patients with diabetic peripheral and autonomic neuropathy. In a randomized placebo controlled study, 50 outpatients were randomly assigned to receive 100 mg minocycline or placebo. Outcome measures included the vibration perception threshold (VPT), Leeds assessment of neuropathic symptoms and signs (LANSS), Pain Disability Index (PDI), Visual Analog Scale (VAS), beck depression inventory (BDI), health assessment questionnaire (HAQ) and autonomic neuropathy, assessed by cardiovascular reflex tests according to Ewing and peripheral sympathetic autonomic function was assessed by FDA approved Sudoscan. At baseline there were no significant differences between demographic variables and the neuropathy variables in the minocycline and placebo groups. After treatment, VPT significantly improved in the minocycline group as compared to the placebo group. Mean posttreatment scores on the LANSS, PDI and HAQ were significantly lower in the minocycline group compared with the placebo group. However, BDI and VAS significantly (p = 0.01) improved in both minocycline and placebo groups (Table 2). After treatment with minocycline, heart rate (HR) response to standing significantly improved, while there was a borderline significance toward a reduction in HR response to deep breath. These finding indicate that 6-week oral treatment with minocycline is safe, well tolerated and significantly improves peripheral and autonomic neuropathy in type 2 diabetic patients.     

Spironolactone improves endothelial dysfunction in ankylosing spondylitis

Chronic inflammation in ankylosing spondylitis (AS) is associated with vascular endothelial dysfunction which leads to accelerated atherosclerosis. Accelerated atherosclerosis contributes to premature cardiovascular disease and increased cardiovascular mortality in AS. Spironolactone inhibits the production of proinflammatory cytokines and improves endothelial dysfunction in rheumatoid arthritis. This study aimed to determine the effect of spironolactone in antitumor necrosis factor (TNF)-naive AS patients. Twenty anti-TNF-naive AS patients (M/F?=?15/5) with high disease activity (Bath ankylosing spondylitis disease activity index, BASDAI >4) despite treatment with stable doses of conventional disease-modifying antirheumatic drugs were investigated. Inflammatory disease activity (BASDAI and Bath ankylosing spondylitis functional index (BASFI) scores, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels), serum nitrite concentration, and endothelium-dependent and -independent vasodilatation of the brachial artery were measured at baseline and after 12 weeks of therapy with oral spironolactone 2 mg/kg/day. Ten healthy subjects matched for age and sex acted as the control. Flow-mediated dilation (FMD) in AS patients at baseline was significantly impaired compared with healthy control group (p?<?0.001). After treatment, FMD improved from 11.3?±?1.70 to 24.69?±?2.34 % (p?<?0.001); nitrite concentration reduced from 7.9?±?0.28 to 4.79?±?0.19 μmol/L (p?<?0.001); ESR from 33.8?±?4.38 to 15.13?±?1.30 mm in the first hour, (p?<?0.001); and CRP level from 22.39?±?3.80 to 6.3?±?1.29 mg/dL, (p?<?0.001). BASDAI and BASFI also reduced significantly (p?<?0.001). The study suggests that in AS endothelial dysfunction is a part of the disease process. This is the first study to show that treatment with spironolactone improves both endothelial dysfunction and inflammatory disease activity in AS.