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)

Anti-inflammatory therapy with monoclonal antibodies (mAbs) directed against tumour necrosis factor (TNF)-alpha has emerged as a major advancement in the treatment of various immune mediated diseases such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and Crohn's disease. TNF-alpha seems to play a major pathogenic role in these chronic immune-mediated inflammatory diseases. Infliximab (Remicade), Centocor, Inc., Malvern, PA, USA), a chimaeric mAb, binds to soluble and membrane bound TNF-alpha, but not to TNF-beta. Infliximab is able to effectively regulate and mediate inflammatory processes involved in a number of different disease states. Many clinical trials in these diseases have demonstrated that biological therapy with mAbs directed against TNF-alpha is effective and relatively safe.
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PMID:Overview of the use of the anti-TNF agent infliximab in chronic inflammatory diseases. 1271 38

The therapeutic options for patients suffering from severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is now accumulating evidence that anti-TNF therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Based on the data recently published on what is now several hundred AS and PsA patients, this treatment seems to be even more effective than the same therapy in rheumatoid arthritis (RA). The anti-TNF-alpha agents currently available, infliximab (Remicade); Centocor), etanercept (Enbrel); Amgen) and adalimumab (Humira; Abbott), are approved for the treatment of RA in the US; infliximab and etanercept are approved in Europe. The situation in SpA is different to RA because there is an unmet medical need, especially in AS, since no therapies with disease-controlling antirheumatic drugs are available for severely affected patients, especially with spinal disease. Thus, TNF blockers might even be considered as first-line immunosuppressive agents in patients with active AS and PsA who are not sufficiently treated by non-steroidal anti-inflammatory drugs and sulfasalazine, if peripheral arthritis is present. For infliximab, a dosage of 5 mg/kg at intervals between 6 and 12 weeks was necessary to constantly suppress disease activity; this is also a major aim of long-term treatment. No dose-finding studies have yet been performed. The standard dose of etanercept is 25 mg s.c. twice-weekly. No studies on adalimumab (standard RA dose 20 - 40 mg s.c. every 2 weeks) have yet been conducted in SpA. The efficacy of etanercept was first demonstrated in PsA and etanercept is now approved for this indication. A double-blind study has also been performed in AS, with similarly clearcut efficacy. There is preliminary evidence that both agents do also work in other SpA such as undifferentiated SpA. Infliximab has recently been approved for short-term treatment of severe uncontrolled AS; the approval for etanercept is pending. Studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis might be preventable but it remains to be shown whether patients benefit from long-term anti-TNF therapy and whether radiological progression and ankylosis can be stopped. Severe adverse events have remained rare. Complicated infections including tuberculosis have been reported. Tuberculosis can be mostly prevented if patients are checked for previous contact with tuberculosis. Currently, the benefits of anti-TNF therapy in AS seem to outweigh these shortcomings.
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PMID:Novel approaches in the treatment of ankylosing spondylitis and other spondyloarthritides. 1283 46

There is no reference second-line treatment for patients with rheumatoid arthritis, juvenile chronic arthritis, psoriatic arthropathy or ankylosing spondylitis after failure or intolerance of a slow-acting antirheumatic drug such as methotrexate. Etanercept, a immunosuppressant targeting TNF-alpha (like infliximab), is now approved in France for use in these situations, with the exception of spondylitis. In the second-line treatment of adults with rheumatoid arthritis, the clinical evaluation dossier on etanercept contains data from dose-finding studies and two placebo-controlled trials involving patients in whom several single-agent treatments had failed. At a dose of 25 mg subcutaneously twice a week, etanercept worked partially in about half the patients. Without direct comparisons, the place of etanercept relative to other slow-acting antirheumatic drugs is difficult to establish. From indirect comparisons, etanercept seems a slightly better treatment option than infliximab. In the first-line treatment of rheumatoid arthritis, one trial showed that etanercept worked faster than methotrexate, but there was no significant difference between the two treatments after two years. Little is known about the efficacy of etanercept in patients with juvenile chronic arthritis who do not respond adequately to methotrexate. There are no comparative trials. One double-blind placebo-controlled trial showed that etanercept, when it worked, remained active for at least 7 months. In one trial, etanercept was more effective than placebo in patients with psoriatic arthropathy and ankylosing spondylitis who continued to receive their usual treatment, which included a slow-acting antirheumatic drug in about 50% of cases. More than 50% of patients treated with etanercept have a cutaneous reaction to the injection. These reactions are usually mild or moderate. Active pharmacovigilance is needed, given its mechanism of action, and previous notifications of a wide variety of adverse effects (even though it is sometimes difficult to establish a foolproof link between etanercept and the adverse effect). Long-term studies of large numbers of patients are needed to determine the precise risk of side effects including haematological, infectious, neurological, oncological and immunological effects. In practice, methotrexate remains the first-line treatment for inflammatory arthritis. Etanercept can be a useful second-line treatment, especially in juvenile chronic arthritis.
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PMID:Etanercept: new preparation. Useful after methotrexate failure in inflammatory rheumatism. 1290 20

The topics discussed at this conference covered many aspects of the pathogenesis, epidemiology, diagnosis and treatment of rheumatic diseases, from the search of new therapeutic targets and evaluation of new diagnostic techniques to preclinical and clinical development of novel therapies. This contribution focuses primarily on two issues that dominated this meeting. First, a number of interesting studies presented during this conference examined the possible value of novel selective therapies directed against recently identified targets of the immune system including cytokines (TNF-alpha, IL-6, IL-15) and inflammatory cells, such as B cells, CD4(+) T cells or memory/effector T cells. Second, clinical experience with newer anti-inflammatory treatments, such as TNF-alpha-blocking agents or leflunomide, is growing judging by the number of reports of their use in clinical practice and new indications. Several studies presented at this meeting examined the value of currently licensed drugs in new indications, such as ankylosing spondylitis or psoriatic arthritis, or studied new combinations of drugs, for example, a combination of different biological treatments (e.g., anakinra, etanercept), in already established indications. Interestingly, the results of these studies were not always as expected, thus increasing the importance of these particular trials. The growing experience with some of these novel therapies clarify the role of these treatments in particular forms of rheumatic diseases and will help to develop guidelines for the use of these sometimes powerful but also possibly harmful agents in clinical practice.
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PMID:The Annual European Congress of Rheumatology: recent advances in the treatment of rheumatic diseases. Lisbon, Portugal, June 18-21, 2003. 1451 90

CLASSICAL DATA: Spondyloarthropathies regroup several rheumatological entities (ankylosing spondylitis, reactive arthritis, psoriatic rheumatism, entero-colopathic disease rheumatism, undifferentiated spondyloarthropathies ) with validated diagnosis criteria. Drug therapy is based upon NSAIDs (non-steroidal antiinflammatories). Refractory forms may lead to severe functional impairment, raising the need of more effective treatments. IN FAVOUR OF ANTI-TNF-ALPHA AGENTS: Several arguments (TNF-alpha serum levels, elevated levels of mRNA, TNF messengers, in sacro iliac biopsies, efficacy of anti TNF-alpha agents in Crohn's disease ) justify the use of anti-TNF-alpha agents in the treatment of spondyloarthropathies. Two biologic agents have been assessed in these circumstances: a monoclonal antibody (Infliximab) and a soluble form of the TNF receptor (Etanercept). EFFICACY AND SAFETY: Results of open and controlled studies, although on small series, demonstrated the significant efficacy of anti-TNF-alpha agents on the various clinical, biological, functional and quality of life parameters, and confirmed by imaging (MRI ). Tolerance is fair, but two cases of diffuse tuberculosis have been reported with Infliximab. THERAPEUTIC PROGRESS: Even if additional studies are required to answer some questions (long term efficacy and safety, treatment modalities), anti TNF agents appear as a therapeutic progress in refractory spondyloarthropathies, for which few validated options have existed up till now.
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PMID:[Therapeutic use of anti-TNF-alpha agents in spondyloarthropathies]. 1453 71

Tumour necrosis factor (TNF) is a pro-inflammatory cytokine with a role in the pathogenesis of a number of conditions including rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease. Etanercept (Enbrel; Immunex Corp., Seattle, WA, USA) is a recombinant soluble fusion protein of TNF-alpha type II receptor and IgG which acts by blocking the action of TNF-alpha. It is licensed for use in rheumatoid arthritis and juvenile chronic arthritis. A number of studies report the development of antinuclear and anti-double-stranded DNA antibodies in patients treated with TNF antagonists for rheumatoid arthritis. There are few reports of the development of clinical features of discoid, subacute or systemic lupus erythematosus. We present one of the first reported cases of etenercept-induced systemic lupus erythematosus and review the literature of lupus and TNF antagonists.
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PMID:Etanercept-induced systemic lupus erythematosus. 1461 25

Reactive arthritis (ReA) is an aseptic form of articular inflammation induced by infections mainly localised in the gastrointestinal (enteroarthritis) or urogenital (uroarthritis) tracts. The bacteria principally involved as causative agents are Chlamydia, Salmonella, Shigella, Campylobacter and Yersinia. The clinical picture is usually characterised by a mono-oligoarthritis of the lower limbs. Axial involvement is possible and extra-articular manifestations such as enthesitis, tenosynovitis, bursitis and dactylitis are frequent. NSAIDs and sulfasalazine are still the drugs most commonly used in the treatment of ReA. Steroids are administered when inflammatory symptoms are resistant to NSAIDs. Experiences with other DMARDs (disease modifying antirheumatic drugs) such as azathioprine, methotrexate and cyclosporin, have been sporadically reported and they can be employed in patients that are unresponsive to the more usual medicaments. The intake of antibacterials (tetracyclines) may be useful in uroarthritis but have not been so successful in enteroarthrits. In more aggressive cases, or when ReA evolves towards ankylosing spondylitis, TNF-alpha blockers could represent an effective choice.
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PMID:Management of reactive arthritis. 1468 Apr 36

As advances in the treatment of ankylosing spondylitis continue, TNF-alpha blocking agents may eventually be used as a first-line treatment. MR imaging could then be used to aid in the early diagnosis of ankylosing spondylitis by identifying early sacroiliitis, followed by immediate initiation of treatment to prevent the progression of the disease with its accompanying morbidities. Currently, radiographic identification of sacroiliitis remains the mainstay in diagnosing ankylosing spondylitis. In ankylosing spondylitis and psoriasis, MR imaging can demonstrate areas that are undergoing active inflammatory changes and enthesitis, aiding in the diagnosis of a spondyloarthropathy.
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PMID:Spondyloarthropathies: ankylosing spondylitis and psoriatic arthritis. 1504 27

The recent development of inhibitors of TNF-alpha has provided the opportunity for a more targeted and highly effective approach to the treatment of chronic inflammatory illnesses such as rheumatoid arthritis. Since the initial approval of etanercept as a treatment for rheumatoid arthritis, additional indications, including psoriatic arthritis, juvenile rheumatoid arthritis and ankylosing spondylitis, have also received FDA approval. More than 220,000 patients have been treated with etanercept so far. This review summarises the body of knowledge accumulated so far on etanercept (Enbrel) since it entered the market 5 years ago.
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PMID:Etanercept: a clinical review of current and emerging indications. 1515 16

Infliximab was the first anti-TNF agent used to treat rheumatoid arthritis to provide proof of concept of the role of TNF-alpha in this condition. It has become widely used since, principally as an effective treatment in combination with methotrexate, but also as monotherapy for the treatment of Crohn's disease, ankylosing spondylitis,and psoriatic arthritis. The benefits of infliximab in controlling signs and symptoms, improving quality of life, preventing structural joint damage, and possible healing of bone provide an important option for the treatment of rheumatoid arthritis.
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PMID:Infliximab treatment of rheumatoid arthritis. 1517 44


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