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

The case of a 50 year old male with the Fiessinger-Leroy-Reiter syndrome, ankylosing spondylitis and generalised pustular psoriasis is reported. This condition wax complicated by non-obstructive cardiomyopathy, congestive cardiac failure and first-degree atrioventricular block, the site of which was localised by electrophysiological studies (nodal block with an infrahisian conduction defect). After failure of several therapeutic regimes, a spectacular improvement was obtained with Methotrexate associated with a diuretic; the signs of heart failure regressed and the cardiomyopathy stablised. A parallel improvement was seen in the skin, cardiac and articular lesions and has been maintained with an 18 months follow-up. Left ventricular performance was studied by echocardiography. The mechanism of the beneficial effect of Methotrexate is unclear; this therapeutic trial is to be extended to include other cases of primary cardiomyopathy without obstruction.
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PMID:[Fiessinger-Leroy-Reiter syndrome with non-obstructive cardiomyopathy treated with methotrexate]. 11 79

The literature concerning second-line treatment of seronegative spondylarethropathies from 1940 to August 1993 was reviewed. Sulfasalazine appeared to be effective in the treatment of ankylosing spondylitis (AS) and promising in reactive arthritis (ReA) and Reiters' syndrome (RS). Methotrexate and azathioprine were associated with a remarkable improvement in some cases of AS and RS. Methylprednisolone and levamisole were both efficacious in AS, but levamisole was associated with occasional severe side effects. Radiation therapy led to short-term improvement in AS, but was abandoned because of severe long-term side effects. Only sulfasalazine has been studied in sufficient detail to allow definitive conclusions, but methotrexate and azathioprine may be promising drugs.
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PMID:Second-line treatment in seronegative spondylarthropathies. 783 56

Methotrexate (MTX) is one of the most effective treatments of rheumatoid arthritis. It has also been used in other conditions such as spondylarthropathies (SPA). The literature concerning MTX in SPA was reviewed. Thus, MTX has been mainly prescribed in psoriatic arthritis and Reiter's syndrome with success for dermatological manifestations of these diseases. However, only a few controlled trials have been conducted in psoriatic arthritis and only one placebo controlled study did not demonstrate a real beneficial effect. Furthermore, it seems that MTX has no influence on the radiological outcome of psoriatic arthritis. There has been no controlled study upon the efficacy of MTX in Reiter's syndrome, ankylosing spondylitis or arthropathy associated with inflammatory bowel diseases. Such studies in SPA are required to evaluate the responding conditions, the efficacy, the side-effects, and the effective dose of MTX.
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PMID:[Use of methotrexate in spondylarthropathies. Review of the literature]. 876 99

The aim of the study was to evaluate the efficacy of methotrexate treatment in patients with ankylosing spondylitis in a 3-year open trial. Seventeen patients, 14 men and three women (mean age 32.7+/-8.9 years), suffering from ankylosing spondylitis and non-responders to treatment with sulphasalazine, were enrolled in our study. Sixteen of them were evaluable at the end of the study. Methotrexate (7.5-10 mg/week) was administered for 3 years. Efficacy was evaluated on the basis of clinical and laboratory variables, radiographic signs of disease progression and daily dosage of indomethacin. We obtained a good and relatively prompt clinical response except for peripheral arthritis and iridocyclitis; in fact, after 3 months of methotrexate treatment a significant amelioration of the following parameters was observed: visual analogue scale for the evaluation of both night pain and general well-being, Shober's test, occiput-wall distance, fingertip to floor, erythrocyte sedimentation rate, C-reactive protein level and daily dose of indomethacin. A further improvement was obtained during the subsequent period. Radiographs of the spine and sacroiliac joints did not show any signs of disease progression. Side-effects were a transitory elevation of transaminases (four cases) and slight hypogammaglobulinaemia (one case). Methotrexate treatment may be useful in ankylosing spondylitis, but a combined treatment might be indicated for patients with peripheral arthritis.
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PMID:Efficacy of methotrexate in the treatment of ankylosing spondylitis: a three-year open study. 1079 21

As erosive and deforming arthritis is present in 40% of patients with psoriatic arthritis (PsA), early and aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) may be as effective in controlling the progression of the disease as it is for rheumatoid arthritis (RA). Methotrexate (MTX), sulfasalazine (SSZ), and cyclosporine (CsA) are the most widely used DMARDs in the treatment of PsA and are safe and effective in patients with active peripheral arthritis, although they do not appear to be effective on axial manifestations. No controlled study has evaluated the efficacy of these drugs on the progression of radiological damage. It has recently been demonstrated that leflunomide and anti-tumor necrosis factor (TNF) agents are effective in PsA and psoriasis. The symptomatic improvement has been important and sustained and side effects minimal. In particular, inhibitors of TNF appear to have excellent potential to treat PsA. These agents are able to slow joint damage in rheumatoid arthritis and they are effective on spinal symptoms in ankylosing spondylitis. Hopefully, these findings will prove true in PsA as well.
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PMID:Disease-modifying antirheumatic drug therapy for psoriatic arthritis. 1246 52

Information concerning the effectiveness of drug therapy cannot be obtained only from randomized controlled clinical trials, due to limitations such as a short time frame and narrow inclusion and exclusion criteria. Therefore, complementary longitudinal observational studies performed in a real life setting are required. NOR-DMARD, a Norwegian 5-center register, was established in December 2000. All DMARD prescriptions to patients with inflammatory arthropathies are included, and patients are followed longitudinally with a variety of assessments. As of 2005, 4683 DMARD regimens have been included. Methotrexate is the most commonly used DMARD in rheumatoid arthritis and psoriatic arthritis. The proportions of patients who have received anti-TNF drugs in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile arthritis and other diseases have been 22.5, 21.6, 53.8, 36.9 and 9.7%, respectively. The proportion of patients receiving anti-TNF drugs is considerably higher in 2004 than earlier, and criteria for prescribing anti-TNF drugs appear to be trending toward patients with less severe and active disease. Confounding by indication or channeling bias represents a challenge for the group comparisons of longitudinal effectiveness data, but can be addressed by modern statistical techniques. The NOR-DMARD register may in the future provide comparative real life effectiveness data that may also be used in cost-effectiveness analyses.
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PMID:A Norwegian DMARD register: prescriptions of DMARDs and biological agents to patients with inflammatory rheumatic diseases. 1627 6

The main objectives of medical therapy in ankylosing spondylitis (AS) are to relieve pain, stiffness and fatigue and to prevent structural damage. The Assessment in Ankylosing Spondylitis Working Group has proposed different domains with specific instruments to assess the efficacy of therapeutic agents classified as symptom-modifying and disease-controlling antirheumatic drugs. Non-steroidal antiinflammatory drugs (NSAIDs) are still the first-line treatment in the management of AS, and they are effective in controlling symptoms such as pain and stiffness and maintaining mobility in many patients. A recent randomized trial suggested that the progression of radiological damage occurs less on continuous use of celecoxib compared with on-demand use. If such findings were confirmed by other studies, the therapeutic value of NSAIDs in AS may extend beyond symptom control. However, for each individual patient, the expected advantages of treatment with NSAIDs should be weighted against any possible gastrointestinal and cardiovascular disadvantages. Disease-modifying antirheumatic drugs (DMARDs) are widely used for second-line therapy in AS, but the evidence for their efficacy is poor. The term 'DMARD' has been borrowed from rheumatoid arthritis, and none of the DMARDs have been shown to prevent or significantly decrease the rate of progression of structural damage which is required to be qualified as a disease-controlling antirheumatic drug for AS. Sulphasalazine is the most extensively studied DMARD and studies suggest some degree of clinical benefit confined to peripheral joint involvement, but no evidence of benefit in axial disease. Methotrexate, which is the gold standard DMARD in rheumatoid arthritis, does not seem to have a substantial therapeutic effect in AS on axial or peripheral joint involvement. Leflunomide appears to exert little beneficial effect, if any, even on peripheral joint involvement. There is also good evidence that local therapy with corticosteroids is effective and may be used in selected patients. Oral corticosteroids may be somewhat effective in relieving the symptoms of AS, but this has not been formally studied. Small studies have reported favourable results with intravenous methylprednisolone pulse therapy, but the effect is temporary. Pamidronate and thalidomide have been used in some preliminary trials but need further studies to assess their potential role in treating AS patients resistant or intolerant to other forms of treatment. Treatment with tumour necrosis factor blockers is not discussed in this review.
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PMID:Ankylosing spondylitis and symptom-modifying vs disease-modifying therapy. 1677 81

Ankylosing spondylitis (AS) is a chronic, immunologically mediated rheumatic disease whose progression largely depends on the extent of inflammatory activity. In contrast to rheumatoid arthritis (RA), therapeutic control of AS is very limited. Therapy of ankylosing spondylitis should not only control inflammatory processes, but also prevent structural damages and maintain the functions. Until recently, physiotherapy and non-steroidal antiphlogistics (NSA) therapy was a gold standard of AS treatment. NSA therapy alleviates inflammatory pain of spine in 60 to 80% of patients. According to the most recent findings, long-term administration of NSA can affect also X-ray progression. DMARD therapy, which is efficient in RA, has insignificant effect on axial form of AS. Sulfasalazine proved to be efficacious against peripheral form of AS; administration of MTX and leflunomide is not supported by controlled studies. Peripheral arthritis and enthesitis is usually treated by short-term application of corticoids. The fact remains that an important role in AS immunopathogenesis is played by TNF alpha whose increased levels were found in patients with AS in serum, synovial fluid and SI joints. Anti-TNF therapy with infliximab and etanercept proved to be highly efficacious in patients with AS resistant to conventional therapy. Infliximab and etanercept reduced the disease activity (50% improvement in more than half of patients), improved the function and slowed down the structural damage. MRI studies of anti-TNF therapy proved reduction of inflammatory activity in SI joints and spine. Other studies verified the efficacy of adalimumab in AS therapy and showed that adalimumab is a promising drug. Also, several randomized clinical studies proved efficacy of thalidomide whose administration, however, is limited by its severe adverse effects. Until now, the results of studies focused on pamidronate therapy appear to be rather controversial. Better understanding of AS pathogenesis led to implementation of new therapeutic procedures that significantly improve activity and functional condition of patients.
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PMID:[Ankylosing spondylitis--the current situation and new therapeutic options]. 1696 16

Homocysteine (Hcy), a sulfur-containing amino acid, is eliminated through B vitamins-dependent pathways. Hyperhomocysteinemia has been found to be an independent risk factor for atherosclerotic cardiovascular, cerebrovascular, and peripheral vascular diseases. Recently, psoriasis, lupus, and rheumatoid arthritis were reported to be associated with hyperhomocysteinemia. This study was aimed to evaluate the changes of plasma Hcy level before and after sulfasalazine and MTX therapy in patients with ankylosing spondylitis (AS). One hundred and two patients with AS and ten normal controls were enrolled in the cross-sectional case-control study. Fasting plasma Hcy levels were determined by ELISA kits (IMX, Abbott). Hcy levels were compared to their Bath AS disease activity index (BASDAI) and the usage of sulfasalazine and/or MTX. Active disease was defined by BASDAI as more than 3 in a 10-cm scale with ESR >20 mm/h. For those patients with plasma Hcy >or=15 micromol/l, a perspective trial of daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg for 2 weeks were also tested for the efficacy. Plasma Hcy level increased significantly in AS patients under sulfasalazine (10.4+/-3.8 micromol/l, p<0.05), MTX (11.9+/-4.7, p<0.05) and sulfasalazine/MTX combination treatment (11.2+/-2.6, p<0.05) compared with normal controls (8.6+/-1.2 micromol/l) and AS patients without DMARD(9.4+/- 2.6 micromol/l). No correlation between disease activity and plasma Hcy level was found. Daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg can lower Hcy level in 2 weeks (32.3+/-24.0 vs 15.6+/-11.1 micromol/l, p=0.007). Plasma homocysteine level did significantly increase in AS patients under sulfasalazine or MTX treatment. B-vitamins should be considered as a routine supplementation for patients who underwent sulfasalazine and/or MTX treatment. Further longitudinal studies are required to confirm the conclusions.
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PMID:Plasma homocysteine status in patients with ankylosing spondylitis. 1702 18

Joint involvement associated with inflammatory bowel disease (IBD) belongs to the concept of spondyloarthritis (SpA) and includes two types of arthritis: a peripheral arthritis characterized by the presence of pauciarticular asymmetrical arthritis affecting preferentially joints of lower extremities and an axial arthropathy including inflammatory back pain, sacroiliitis and ankylosing spondylitis (AS). Treatment of arthritis includes a short-term use of NSAIDs associated with optimized treatment of gut inflammation. Safety concerns mean that long-term treatment with NSAIDs is best avoided if possible. Salazopyrine can be recommended for treatment of peripheral arthritis. Methotrexate and azathioprine are generally ineffective. Finally, efficacy of anti-TNF therapy (infliximab and adalimumab) is well established. However, use of etanercept is not recommended because of the increased risk for intestinal disease relapse. Pathogenesis of gut-joint iteropathy is not elucidated. Both inflammations are tightly related as suggested by human evidence of gut inflammation in patients with other forms of SpA and animal evidence of gut and joint inflammation in HLA-B27/human beta(2)-microglobulin transgenic rat model and TNF(DeltaARE) mice. Several clues for the linkage between gut and joint inflammation have been put forward including an altered recognition and handling of bacterial antigens, an aberrant trafficking of CD8+ T cells with an impaired T-helper type 1 cytokine profile and expression of aEb7 integrin, an altered trafficking of macrophages expressing CD163 and evidence of an increased angiogenesis. A transcriptome analysis of mucosal biopsies identified a set of 95 genes that are differentially expressed in both CD and SpA as compared with healthy controls suggesting common pathways. TNF plays a key role in the pathogenesis of various arthritic diseases and IBD. Mesenchymal/myofibroblast-like cells may represent the local primary targets of TNF in the induction of gut and joint pathology. Selective expression of TNFRI on these cells seems to be sufficient to orchestrate the complete development of SpA-related pathologies at least in TNF(DeltaARE) mice. Finally, genetic susceptibility is probably required to develop these pathologies. Genotyping of AS patients provided evidence for an important overlap between determinants of inherited predisposition to CD and AS. The best documented common association is with an IL-23R polymorphism, although the exact role remains unexplored. In addition, evidence suggests that a number of recently identified CD-susceptibility loci are associated with AS. Clinical, genetical, immunological and therapeutic evidence support the tight junction between gut and joint inflammation in two linked diseases, IBD and SpA, belonging to the 'immune-mediated inflammatory diseases'.
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PMID:Joint involvement associated with inflammatory bowel disease. 1989 67


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