Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
1.
BMC Musculoskelet Disord ; 16: 347, 2015 Nov 11.
Article in English | MEDLINE | ID: mdl-26559487

ABSTRACT

BACKGROUND: Axial spondyloarthropathy typically has its onset in early adulthood and can impact significantly on quality of life. In the UK, biologic anti-tumour necrosis factor therapy is recommended for patients who are unresponsive to non-steroidal anti-inflammatory drugs. There remain several unresolved issues about the long-term safety and quality of life outcomes of biologic treatment in axial spondyloarthropathy. Long-term "real-world" surveillance data are required to complement data from randomised controlled trials. METHODS/DESIGN: We are conducting a UK-wide prospective cohort study of patients with axial spondyloarthropathy who are naïve to biologic therapy at the time of recruitment. Those about to commence anti-tumour necrosis factor biologic therapy will enter a "biologic" sub-cohort with other patients assigned to a "non-biologic" sub-cohort. The primary objective is to determine whether the use of biologic therapy is associated with an increased risk of serious infection, while secondary objectives are to assess differences in malignancy, serious comorbidity, all-cause mortality but also assess impact on specific clinical domains (physical health, mental health and quality of life) including work outcomes between biologic and non-biologic patient cohorts. Patients will be followed-up for up to 5 years. Data are obtained at baseline and at standard clinical follow-up visits - at 3, 6 and 12 months and then annually for the biologic cohort and annually for the non-biologic cohort. This study will also collect biological samples for genetic analysis. DISCUSSION: Although biologic therapy is widely used for ankylosing spondylitis patients who are unresponsive to non-steroidal anti-inflammatory drugs, the majority of the available safety information comes from rheumatoid arthritis, where increased infection risk has consistently been shown. However, given the typical demographic differences between rheumatoid arthritis and axial spondyloarthropathy patients, it is important to develop an epidemiologically rigorous cohort of patients receiving biologic therapy to effectively evaluate outcomes with regard not only to safety but also to quantify benefits across clinical, psychosocial and work outcomes. CLINICAL TRIAL REGISTRATION: This is an observational cohort study and clinical trial registration was not required or obtained.


Subject(s)
Antirheumatic Agents/therapeutic use , Biological Products/therapeutic use , Spondylitis, Ankylosing/drug therapy , Humans , Prospective Studies , Research Design , Rheumatology , United Kingdom
2.
J Allergy Clin Immunol ; 121(5): 1184-1189.e4, 2008 May.
Article in English | MEDLINE | ID: mdl-18313127

ABSTRACT

BACKGROUND: Aspirin can cause bronchoconstriction in some asthmatic patients through increased production of proinflammatory mediators, particularly leukotrienes. However, recent in vivo evidence has suggested that aspirin also triggers the production of lipoxins, which act as natural antagonists of prostaglandins and leukotrienes. Aside from patients with known aspirin-sensitive asthma, physicians have avoided the use of aspirin in asthmatic patients in general because it was believed that this agent might precipitate worsening of their condition. OBJECTIVE: We sought to establish the effect of aspirin on pulmonary inflammation and function in patients with persistent asthma. METHODS: After withdrawal of their usual anti-inflammatory medication, patients with mild-to-moderate persistent asthma undertook double-blind, randomized, crossover treatment with 75 mg/d aspirin and placebo for 3 weeks each. Treatment evaluation included histamine challenge, spirometry, impulse oscillometry, total and alveolar exhaled nitric oxide measurement, and serum thromboxane B2 and 15-epilipoxin A4 levels. RESULTS: Fifteen patients completed the trial. Compared with placebo, there were no differences in histamine PC(20) values (0.17 doubling-dilution shift; 95% CI, -0.38 to 0.73; P = 1), exhaled nitric oxide levels (0.95-fold change; 95% CI, 0.45-2.00; P = 1), or any other inflammatory, spirometric, or oscillometry measurements. Aspirin led to a significant decrease in thromboxane B2 levels (17.53-fold difference; 95% CI, 5.46-56.49; P < .001). Baseline 15-epilipoxin A4 levels were increased at 4.88 ng/mL, and there was no increase with aspirin versus placebo (0.99-fold difference; 95% CI, 0.79-1.24; P = 1). CONCLUSION: In this preliminary study of 15 patients, low-dose aspirin did not lead to increased 15-epilipoxin A4 synthesis or alter inflammatory markers in patients with mild-to-moderate persistent asthma.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Aspirin/adverse effects , Asthma/chemically induced , Lung/drug effects , Adult , Breath Tests , Bronchial Provocation Tests , Double-Blind Method , Female , Humans , Inflammation/chemically induced , Lipoxins/blood , Lung/immunology , Male , Nitric Oxide/metabolism , Placebos , Respiratory Function Tests , Thromboxane B2/blood
3.
J Allergy Clin Immunol ; 119(2): 328-35, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17141851

ABSTRACT

BACKGROUND: Statins lower cholesterol and also exhibit anti-inflammatory properties. In vitro and animal studies have suggested they may be useful for the treatment of a number of inflammatory conditions. OBJECTIVE: To evaluate the in vivo therapeutic potential of simvastatin as an anti-inflammatory agent in patients with asthma. METHODS: Potential signal from treatment effect was optimized by withdrawing all anti-inflammatory treatment for the duration of the study. Participants received 1 month of daily simvastatin and 1 month of daily placebo in a randomized, double-blind crossover trial. A total of 16 patients completed per protocol. Asthmatic inflammation was evaluated by measuring exhaled tidal nitric oxide, alveolar nitric oxide, sputum and peripheral eosinophil count, methacholine hyperresponsiveness, salivary eosinophilic cationic protein, and C-reactive protein. Measurements of dynamic and static lung volumes and of cholesterol were also made. RESULTS: After initial withdrawal of usual asthma medication, there was a 1.43 geometric mean fold increase (ie, 43% difference) in fraction of exhaled nitric oxide (95% CI, 1.15 to 1.78; P = .004). Compared with placebo, simvastatin led to a 0.86 geometric mean fold decrease (95% CI, 0.7 to 1.04; P = .15) in exhaled nitric oxide (ie, a 14% difference), and a -0.18 doubling dilution shift (95% CI, -1.90 to 1.55; P = 1.0) in methacholine hyperresponsiveness. There were no significant differences in other inflammatory outcomes, lung volumes, or airway resistance between simvastatin and placebo. Treatment with simvastatin led to a significant reduction (P < .005) of total and low-density lipoprotein cholesterol. CONCLUSION: There is no evidence to suggest simvastatin has anti-inflammatory activity in patients with asthma. CLINICAL IMPLICATIONS: Simvastatin is not useful for the treatment of asthma.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Asthma/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Simvastatin/therapeutic use , Adult , Asthma/immunology , Cross-Over Studies , Double-Blind Method , Female , Humans , Male , Middle Aged , Nitric Oxide/metabolism , Th1 Cells/immunology , Th2 Cells/immunology
SELECTION OF CITATIONS
SEARCH DETAIL
...