Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the role of tumor necrosis factor-alpha (TNF-alpha) gene as susceptibility marker for spondyloarthritis (SpA), two polymorphisms (-238 and -308 positions) were analyzed in 229 patients with SpA (113 with ankylosing spondylitis [AS], 92 with undifferentiated SpA [U-SpA], 24 with reactive arthritis), and 169 ethnically matched healthy control subjects. The HLA-B alleles were detected by PCR-SSP technique and the TNF-alpha polymorphism by PCR-RFLP. In comparison with healthy control subjects, the frequencies of TNF-238 in SpA were similar. In contrast, the analysis of -308 polymorphism showed increased frequencies of the T2(A) allele in the whole SpA group (p < 0.05, pC = NS, OR = 1.83) as well as the T2(A) allele (pC < 0.05, OR = 2.4) and T1T2(AG) genotype (p < 0.05, pC = NS, OR = 2.25) in U-SpA patients. Comparison of B27-negative patients and healthy control subjects yielded similar results. There was no significant correlation between TNF genotypes and clinical data. The present study demonstrates that TNF-alpha -308 polymorphism appears to be associated with the genetic susceptibility U-SpA. The association seems independent of the susceptibility conferred by the HLA-B27 in this group of patients.
 ...
PMID:Tumor necrosis factor-alpha promoter polymorphisms in Mexican patients with spondyloarthritis. 1705 60

Scoring systems have been developed for radiographs and magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS). Radiographic scores focus on chronic structural alterations, which occur slowly and show little sensitivity to change in the short-term. Recent clinical studies used the modified Stoke ankylosing spondylitis spine score (mSASSS), which evaluates the cervical and lumbar spine. TNF antagonists were found to modify the mSASSS, indirectly supporting a structural effect of these agents. MRI using specific sequences is a potent tool for evaluating inflammation, most notably at the spine. MRI has proved sensitive to change in patients taking TNF antagonists. An outcome measures in rheumatology clinical trials (OMERACT) task force is working on standardizing MRI scores for the spine and sacroiliac joints.
 ...
PMID:Imaging study scores for ankylosing spondylitis. 1706 46

Tumour necrosis factor alpha (TNF-alpha) plays a crucial role in host defence against bacterial infections. Summarizing the results, the findings of immunological and clinical research suggest a higher infection risk in rheumatoid arthritis and ankylosing spondylitis patients receiving anti-TNF treatment. This is especially true for granulomatous infections in patients treated with the monoclonal TNF-alpha antibodies infliximab or adalimumab. Furthermore, patients treated with TNF inhibitors have a higher susceptibility to infections because of their higher active and more severe disease. Therefore, patients receiving anti-TNF treatment should be closely monitored for serious infections. A rapid and sufficient treatment of infections that are not mild and transient is recommended. There are atypical signs and symptoms as well as atypical pathogen that should be considered. Patients should be educated about how to avoid infectious complications.
 ...
PMID:Infection and musculoskeletal conditions: Bacterial and opportunistic infections during anti-TNF therapy. 1712 3

Biological therapy for ankylosing spondylitis (AS) has led to improved disease control beyond that of conventional treatments. International recommendations encourage clinicians prescribing biological treatments to register patients in national registers to collect information on outcome and toxicity. Patients with AS (n = 229) from the Register of Biological Treatment in Finland (ROB-FIN) with severe disease of long duration were followed-up for up to 24 months. Due to an active disease, one or more concomitant disease-modifying antirheumatic drugs (DMARDs) were used by 86% at commencement of biological therapy. This add-on strategy with infliximab led to a rapid pain relief and improvement of patient's and physician's global assessments, C-reactive protein/erythrocyte sedimentation rate, and swollen and tender joint counts within 6 weeks. Concomitant use of NSAID and oral corticosteroid was reduced. Corresponding results were documented at 3 months with etanercept, which was more recently approved for the treatment of spondyloarthropathies. Seventy-nine percent of the patients were ASAS 20 responders. A subgroup of AS patients with only axial involvement (n = 46) responded correspondingly. The first biological drug was discontinued in only 7% due to lack of efficacy and in 6% due to adverse events. Anti-TNF agents, often used in combination with DMARDs, appeared to have persistent effectiveness and limited toxicity in a real-life clinical setting in a cohort of Finnish AS patients with severe disease and long disease duration.
 ...
PMID:Anti-TNF therapy in the treatment of ankylosing spondylitis: the Finnish experience. 1733 79

Ankylosing spondylitis is a chronic inflammatory disease, with a prevalence of approximately 0.5%, which starts in the third decade of life. Treatment was, until recently, limited. Conventional disease-modifying drugs are not effective for the spinal manifestations, and NSAIDs and physical therapy were the standard treatment, without any other options for patients who did not respond to this treatment. Therefore, the high efficacy of the new group of TNF-blockers for the treatment of active ankylosing spondylitis represents a breakthrough for NSAID-refractory patients. Following the introduction of the two TNF-blockers, infliximab and etanercept, the fully humanized, anti-TNF monoclonal antibody adalimumab is now the third product that has been approved for the treatment of ankylosing spondylitis. Adalimumab is given subcutaneously every 2 weeks at a dose of 40 mg. In open and placebo-controlled trials, the drug was shown to be safe and effective in ankylosing spondylitis patients. Long-term treatment data of up to 2 years are now available, confirming efficacy and acceptable safety.
 ...
PMID:Adalimumab for the treatment of ankylosing spondylitis. 1742 78

The concept of biological therapy arises from the specific targeting of a factor, e.g. a cytokine, involved in the inflammatory cascade. Thus, biologicals disrupt the complex network of autoimmune-inflammatory events. Today, rheumatoid arthritis is a prototype disease in this context as most compounds have been tried in this disease. Recently, biological therapy has been introduced to the treatment of other diseases including various forms of arthritis, such as ankylosing spondylitis and psoriatic arthritis, as well as systemic autoimmune disorders, such as systemic lupus erythematosus, scleroderma, inflammatory myopathies and Sjogren's syndrome. Anti-tumor necrosis factor-alpha (TNF-alpha) agents play a central role in biological therapy as these agents have been successfully tried in most of these diseases. When seeking for specific targets for biologicals, pathogenic factors of the disease, such as Th1 or Th2 type responses, should be evaluated. Some mostly T-cell mediated diseases, such as rheumatoid arthritis, ankylosing spondylitis, psoriasis, polymyositis, polyarticular juvenile arthritis respond well to anti-TNF agents and T cell targeting, while others, such as lupus, Sjogren's syndrome, dermatomyositis may rather respond to anti-B cell biologicals. In this review, authors discuss the most recent advances in the biological therapy of arthritis and systemic autoimmune diseases including issues of efficacy and safety.
 ...
PMID:[Biological therapy of arthritis and systemic autoimmune diseases]. 1743 Jul 97

It has been well known that anti-TNF drugs might increase lymphoma risk in rheumatoid arthritis (RA), where the rate of lymphoma has already been increased. However, unlike RA, an increased rate of lymphoma has not been reported in ankylosing spondylitis (AS). Hereby, we present a case with AS developing Hodgkin's lymphoma (HL) following 6 months of etanercept treatment. Pathological analysis revealed mixed cellular type of HL. Although we report a single case, it should be kept in mind that anti-TNF drugs might cause lymphoma development not only in RA, but also in AS.
 ...
PMID:Hodgkin's lymphoma following treatment with etanercept in ankylosing spondylitis. 1762 34

Tumor necrosis factor-alpha (TNF-alpha) plays an important role in the pathogenesis of such diseases as rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, and juvenile chronic arthritis. Recent years have brought improvement in the understanding of the pathogeneses of these diseases, resulting in the production of new groups of biological drugs, including, among others, anti-TNF-alpha antibodies. The use of TNF inhibitors has been a great advance in the treatment of patients with these inflammatory diseases. Infliximab and adalimumab are monoclonal antibodies that bind to and neutralize the activity of TNF-alpha. Infliximab is a mouse/human chimera that joins the variable regions of a mouse antibody to the constant region of human IgG1. Adalimumab is a fully human IgG1 antibody. Etanercept is a dimeric fusion protein that joins the human p75 TNF receptor to the Fc domain of human IgG1. The beneficial effects of the anti-TNF monoclonal antibodies infliximab and adalimumab and the soluble receptor fusion protein etanercept in the treatment of rheumatoid arthritis, especially in patients resistant to other disease-modifying antirheumatic drugs (DMARDs), are discussed. We observe stoppage of articular destruction during treatment with TNF-alpha inhibitors. Soon after the introduction of this therapy it was found that these agents have a propensity for stimulating the production of autoantibodies and antibodies against themselves. In this review, recent studies analyzing the effect of TNF-alpha blockade (infliximab, etanercept, and adalimumab) on the ANA, anti-dsDNA, and anticardiolipin antibody profiles in autoimmune diseases are discussed.
 ...
PMID:[Autoimmune aspects of treatment with TNF-alpha inhibitors]. 1778 35

The nucleotide-binding domain, leucine-rich repeat containing family (NLR) network has provided pivotal genetic and molecular insights into diseases that were hitherto regarded as autoimmune. The NLR-related disorders include rare monogenic autoinflammatory diseases collectively termed cryopyrin-associated periodic syndromes, Crohn's disease which is a common polygenic disease and also an association at the mechanistic level with gout and pseudogout. Unlike the classical autoimmune diseases where disease immunopathogenesis is played out primarily in the primary and secondary lymphoid organs, the immunopathogenesis of the NLR-related disorders is played out in the tissues where inflammation arises. As the genetic mutations or molecular cascades associated with the NLR-related disorders have a widespread cellular distribution, it has been somewhat enigmatic why these disorders attack certain territories, but not others. This implies that tissue-specific factors in the target organs themselves contribute to disease expression. Such examples include the high abundance of NOD2 expressing cells in the part of the gut most typically afflicted by Crohn's disease and the preferential deposition of crystals in the joints to where inflammation localises in gout and pseudogout. The NLR network is associated principally with increases in TNF or IL-1 production, both of which are key players in innate immunity. Therefore, the NLR network identifies at the genetic and molecular level a robust paradigm for innate immune activation against self. This tissue-specific-factor-associated inflammation is the diametric opposite of classical autoimmunity. Of note, the MHC class-I-associated diseases including psoriasis (HLA-Cw6) and ankylosing spondylitis (HLA-B27) show striking clinical overlaps with Crohn's disease and also some rare monogenic diseases. Thus, the NLR innate immune pathway allows the full spectrum of inflammation against self to be viewed along an immunological disease continuum with autoantibody-associated disease at one end, innate immune diseases at the other and MHC class-1-related disorders as an intermediate.
 ...
PMID:The NLR network and the immunological disease continuum of adaptive and innate immune-mediated inflammation against self. 1780 42

In this study, we compare the health-related quality of life (HRQoL) of patients with moderate-to-severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), and study the effect of treatment with infliximab on the HRQoL of patients with these diseases. Short Form Health Survey-36 (SF-36) data from the placebo-controlled phases of 4 studies of infliximab in patients with inflammatory rheumatic diseases (n = 1990) were evaluated. Data came from the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) (n = 428), the Safety Trial for Rheumatoid Arthritis with REMICADE Therapy (START) (n = 1083), the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) (n = 279), and the Infliximab Multinational Psoriatic Arthritis Clinical Trial II (IMPACT II) (n = 200). SF-36 assessments were made at weeks 0, 10, 30, and 54 in ATTRACT, weeks 0, 6, and 22 in START, weeks 0, 12, and 24 in ASSERT, and weeks 0 and 14 in IMPACT II. All patient populations had significantly impaired physical aspects of HRQoL at baseline relative to the general population of the United States, and the magnitude of impairment was similar across the diseases. Mean baseline physical component summary scores were 29 in the RA cohort, 32 in the PsA cohort, and 29 in the AS cohort. In all 3 diseases, patients who received infliximab showed significant improvement in physical component summary scores compared with those who received placebo. The magnitude of the difference of improvement (effect size, 95%CI) between infliximab and placebo groups was similar in the AS (10.1, 9.2-11.0), PsA (8.6, 7.8-9.4), and RA (10.1, 9.2-11.0) cohorts. Patients with RA and those with PsA treated with infliximab also showed greater improvement in the mental component summary score than those in the placebo group with an effect size of 4.6 (4.2-5.1) in RA and 2.7 (2.4-3.1) in PsA. Patients in large randomized controlled studies of infliximab in RA, PsA, and AS had similar impairment in physical aspects of HRQoL at baseline and showed significantly greater improvement in HRQoL after treatment with infliximab.
 ...
PMID:The impact of infliximab treatment on quality of life in patients with inflammatory rheumatic diseases. 1792 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>