Etanercept Methotrexate

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

The combination of cyclosporine with calcipotriol may be more efficacious than either agent used alone.21,37 Cyclosporine and SCAT may also be effective.21,38 However, cyclosporine should not be used concurrently with PIJVA there is a well-documented increased risk of squamous cell cancer and the combination may have a negative effect on lesion clearance.21 The combination of cyclosporine with methotrexate is extremely effective and minimizes toxicity from either agent as discussed. Cyclosporine has also been used successfully with mycophenolate mofetil38 and etanercept.29... 

Bathon, J.M., Martin, R.W., Fleischmann, R.M., et al. (2001) A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. New England Journal of Medicine. 343,1586-1593. 

Two recently introduced biological therapies were designed to interfere with the inflammatory cascade initiate by TNF-a. Etanercept (Enbrel) is indicated for the treatment of moderate to severe rheumatoid arthritis in individuals over age 4. Infliximab in conjunction with methotrexate (Remicade) is approved for use by adults in the treatment of rheumatoid arthritis. It is also indicated for therapy of Crohn s disease. Over the short term, the efficacy of these drugs in the treatment of rheumatoid arthritis appears to be superior to that of methotrexate alone however, their ability to prevent bone erosion for longer than 24 months must be further studied. The cost of both drugs is significantly higher than that of the other DMARDs. 

When added to methotrexate background therapy, cyclosporine, chloroquine, hydroxychloroquine, leflunomide, infliximab, adalimumab, rituximab, and etanercept have all shown improved efficacy. In contrast, azathioprine, auranofin, or sulfasalazine plus methotrexate results in no additional therapeutic benefit. Other combinations have occasionally been used, including the combination of intramuscular gold with hydroxychloroquine. 

Autoreactive tissue disorders (autoimmune diseases)2 Prednisone, cyclophosphamide, methotrexate, interferon-a and -3, azathioprine, cyclosporine, infliximab, etanercept, adalimumab Often good, variable... 

Etanercept is a dimeric fusion protein composed of human IgGj constant regions (CH2, CH3, and hinge, but not CH ) fused to the TNF receptor. Etanercept binds to both TNF- and TNF-3 and appears to have effects similar to that of infliximab, ie, inhibition of TNF-K-mediated inflammation, but its half-life is shorter due to its physical form (fusion protein) and the route of injection (subcutaneously, twice weekly). Etanercept is approved for adult rheumatoid arthritis, polyarticular-course juvenile rheumatoid arthritis, and psoriatic arthritis. It may be used in combination with methotrexate. 

Treatment with available anti-TN F-a inhibitors can be associated with the development of antibodies to the administered biologies [10]. The incidence is reported to be higher in patients receiving infliximab (13 to 60%), the chimeric monoclonal antibody containing a murine variable region, compared with the incidences reported for the fusion protein etanercept (<5 %) or the fully human antibody, adalimumab (-12% as monotherapy). The observed incidence of antibody formation is reduced by concomitant immunosuppressive therapies, such as methotrexate. Lower efficacy and higher incidences of infusion-related reactions have been reported in antibody-positive patients receiving infliximab [80]. 

Infliximab is used in combination with methotrexate (to reduce anti-mouse antibody formation) and, like etanercept, is reserved for patients with severe rheumatoid arthritis who have failed to respond to adequate trials of at least two DMARDs. In the UK it is licensed only for adults with rheumatoid disease (and for nonhealing fistulae associated with Crohn s disease). 

In a study of weekly oral methotrexate in two different doses (10 or 25 mg) or twice-weekly etanercept in 632 patients, etanercept produced fewer systemic adverse effects than methotrexate, but a higher incidence of injection site reactions (2). Despite theoretical concerns about the development of autoimmune reactions in patients taking etanercept, no evidence of clinical autoimmune disease emerged from this large trial. 

Genovese MC, Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH et al (2002) Etanercept versus methotrexate in patients with early rheumatoid arthritis two-year radiographic and clinical outcomes. Arthritis Rheum 46 1443-1450... 

Criswell LA, Lum RF, Turner KN, Woehl B, Zhu Y, Wang J et al (2004) The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept. Arthritis Rheum 50 2750-2756... 

The clinical effects of Etanercept are comparable to those of Infliximab. One advantage of Etanercept is that it is given subcutaneously twice a week, whereas Infliximab is given by slow intravenous infusion every 4-8 weeks. Another advantage is that Etanercept also recognizes lymphotoxin, and this may account for its efficacy in juvenile chronic arthritis. Currently, D2E7, a fully human anti-TNF antibody, is being developed (Knoll). It appears to be effective in RA without the need for methotrexate cotreatment (575). 

Most clinical trials have used etanercept in patients who failed DMARDs. Response was seen in 60% to 75% of patients. The drug also has been shown to be useful in juvenile rheumatoid arthritis and psoriatic arthritis, for which it is approved by the FDA, and ankylosing spondylitis and other inflammatory arthropathies, for which it is not approved. It has been shown in clinical trials to slow erosive disease progression to a greater degree than oral methotrexate therapy in patients with inadequate response to methotrexate monotherapy." " " ... 

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