Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psoriatic arthritis (PsA) is a partly debilitating disease that may affect small and large joints and the spine. Patients with PsA are divided into different subgroups according to joint involvement and their disease may be classified as part of the spectrum of spondyloarthritides or seronegative rheumatoid arthritis. Traditional treatment comprises nonsteroidal anti-inflammatory drugs, systemic and intra-articular corticosteroids and disease-modifying antirheumatic drugs such as sulfasalazine, methotrexate and cyclosporin. On the basis of the very recent studies performed in the US and Germany, patients with severe disease can be treated with anti-tumour necrosis factor (TNF) therapy. Biologicals such as etanercept and infliximab have been used successfully to treat PsA. While etanercept is a 75kD TNF receptor fusion protein that binds to TNFalpha and TNFbeta, infliximab is a chimeric monoclonal antibody that binds to TNFalpha both in its soluble form in the serum and on the cell membrane. Adalimumab is a fully humanised antibody recognising TNFalpha that has not been tested in PsA to date. Another biological agent, alefacept, is directed against the adhesion molecule lymphocyte function-associated antigen (LFA)-2, which is known to interfere with T-cell activation. Alefacept has been shown to be efficacious in a limited number of patients with PsA. Taken together, there has been definite recent progress in the treatment of PsA. Severely affected patients may especially have substantial benefit from therapy with biologicals directed against TNFalpha and other targets.
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PMID:Role of novel biological therapies in psoriatic arthritis: effects on joints and skin. 1274 55

Alefacept is a novel biologic agent that selectively targets the memory T-cell population involved in the pathogenesis of psoriasis. Alefacept, administered by intramuscular (IM)or intravenous (IV) bolus injection, is safe and efficacious and improves quality of life ina broad spectrum of psoriasis patients. Disease remissions last approximately 7 months in responders following either IM or IV administration without further treatment. In clinical studies, treatment of patients with psoriasis with up to six courses of alefacept demonstrates the following: no evidence of an increased risk for infection or malignancy;no correlation between rates of infection, malignancy, and circulating CD4+ /CD8+ T-cell counts; and low immunogenicity. A preliminary study evaluating the use of alefacept for the treatment of active psoriatic arthritis parallels the psoriasis experience and supports the premise of targeting T cells as an intervention for this disease. Research continues to examine the use of alefacept in combination with other systemic psoriasis therapies and phototherapy and its potential as a treatment for other T-cell-mediated diseases, such as psoriatic arthritis, alopecia areata, and rheumatoid arthritis.
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PMID:Current concepts and review of alefacept in the treatment of psoriasis. 1545 Mar 37

Psoriasis is a chronic inflammatory disease of the skin affecting approximately 2% of the world's population. Traditional systemic treatments, including methotrexate, ciclosporin, psoralen plus UVA (PUVA), oral retinoids and fumaric acid esters, are widely used for severe disease and are effective in the short term. Severe psoriasis is a chronic disease and patients and physicians have expressed concerns about possible harm from organ toxicity, such as skin cancer (PUVA), hyperlipidaemia (retinoids), renal (ciclosporin) or hepatotoxicity (methotrexate). Long-term monitoring is required and may not detect early organ damage. The pathophysiology of psoriasis remains to be clarified, but advances toward the understanding of the immunological basis of psoriasis have uncovered the involvement of immunological pathways; for example, the role of tumour necrosis factor (TNF)-alpha, T cell proliferation and T cell activation, and migration to the epidermis. This advancement in knowledge combined with developments in recombinant technologies has led to the development of target-specific therapies. Biological agents are defined as proteins that can be extracted from animal tissue or produced via recombinant DNA technologies and possess pharmacological activity. Adalimumab, alefacept, infliximab, efalizumab and etanercept are examples of biological agents currently used for the treatment of psoriasis. Some of these are also therapy for other autoimmune conditions, such as rheumatoid arthritis and Crohn's disease. These biological agents are effective in psoriasis but raise new safety concerns. Information on the safety of biological agents in conditions such as rheumatoid arthritis and Crohn's disease can not be directly extrapolated to psoriasis. An increased incidence of lymphomas has been postulated to be associated with etanercept, infliximab and adalimumab; serious infections, such as tuberculosis, have also been reported with these three biologicals, all of which target TNF-alpha. Demyelinating disorders, such as multiple sclerosis, have been reported with some biologicals as has congestive heart failure. Alefacept, because of its mechanism of action of lowering the number of active T cells, is associated with low T cell counts. Efalizumab has been associated with thrombocytopenia and haemolytic anaemia. Data on the safety of >2.5 years' continuous treatment with efalizumab are reassuring and a valuable beginning to understanding the role and risk of harm of long-term therapy for a chronic disease. Longer follow-up studies and safety databases, for each of the biologicals used in psoriasis, are needed to ensure both prolonged efficacy and minimal risk of harm.
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PMID:Fulfilling an unmet need in psoriasis : do biologicals hold the key to improved tolerability? 1645 34