Dmards by fasel rafiq

Dmards by fasel rafiq

1. DMARD’s Presented by : Fasel R afiq Group : 3 Course : 6 th Faculty : General Medicine

2. DMARDs : represent the most important measure in the successful treatment of rheumatoid arthritis. These agents can prevent disease progression and thus joint destruction and subsequent loss of function. Successful DMARD therapy may eliminate the need for other anti-inflammatory or analgesic medications; however, until the full action of DMARDs takes effect, anti-inflammatory or analgesic medications may be required as bridging therapy to reduce pain and swelling.

3. Traditional DMARDs Methotrexate -MTX is a folic acid antagonist that is approved for the management of severe active RA in patients who have had an insufficient therapeutic response to or are intolerant of an adequate trial of first-line therapy, including full-dose NSAIDs . - MTX is started at lower doses and increased to full doses within approximately 4-6 weeks . -The initial dosage is 7.5 mg/wk PO in a single dose; alternatively, the weekly regimen may be administered in divided doses of 2.5 mg PO at 12-hour intervals for 3 doses . -The CBC should be monitored monthly and liver and renal function every 1-3 months during therapy

4. -Leflunomide is indicated for the treatment of active RA to reduce signs and symptoms, inhibit structural damage and improve physical function . - Corticosteroids, aspirin, or other NSAIDs may be continued during leflunomide use . - Leflunomide is contraindicated in women who are or may become pregnant. -Leflunomide is a pyrimidine synthesis inhibitor that blocks autoimmune antibodies and reduces inflammation. - Complete blood counts (CBCs) and liver enzymes must be monitored. Leflunomide -Dose:100 mg PO q Day for 3 day initially, THEN 10-20 mg PO q Day

5. Sulfasalazine - Sulfasalazine is indicated for the treatment of patients with RA who have had an inadequate response to salicylates or other NSAIDs . - It acts locally to decrease inflammatory response and systemically inhibits prostaglandin synthesis . - The initial dosage is 0.5-1 g/day. The dosage can be adjusted to a dose of 3 g/day after 12 weeks if an adequate clinical response is not seen.

6. Hydroxychloroquine -Hydroxychloroquine is approved for the treatment of acute or chronic RA . -The initial dosage is 400-600 mg/day; dosages should be computed on the basis of patient body weight . - If a good clinical response is seen over a period of 4 to 12 weeks, the dosage can be reduced by 50% and continued at a level of 200-400 mg/day. -Patients must have a baseline eye examination (including color and vision testing, funduscopic examination, and visual-field testing) performed before starting HCQ therapy . - Most rheumatologists recommend an HCQ eye examination every 6-12 months.

7. Azathioprine -Although azathioprine is not a first-line agent, it is sometimes used in the treatment of active RA to reduce signs and symptoms, particularly in patients who may have coinciding connective tissue diseases, such as systemic lupus erythematosus . -The mechanism whereby azathioprine affects autoimmune diseases is unknown; however, it works primarily on T cells. - The initial dosage is 1 mg/kg/day (50-100 mg/day) given as a single dose or in divided doses twice daily . - The dosage may be increased by 0.5 mg/kg/day at 6-8 weeks and thereafter at 4-week intervals, up to a maximum dosage of 2.5 mg/kg/day

8. Cyclosporine -Although cyclosporine is approved for the treatment of patients with severe active RA in which the disease has not adequately responded to MTX, it is not commonly used to treat RA, because of its nephrotoxicity . -When cyclosporine is used, patients' renal function must be closely monitored. -Cyclosporine can be used in combination with MTX in RA patients who do not have an adequate response to MTX alone . - The initial dosage is 2.5 mg/kg/day divided twice daily. The onset of action generally occurs between 4 and 8 weeks. The dosage may be titrated to a maximum of 4 mg/kg/day .

9. DMARDs, TNF Inhibitors -The recognition of TNF-α and IL-1 as central proinflammatory cytokines has led to the development of agents that block either these cytokines or their effects . -The TNF inhibitors, which bind TNF and thus prevent its interaction with its receptors, include etanercept , infliximab , golimumab , certolizumab , and adalimumab . - Consensus statements do not recommend their use until at least one xenobiotic DMARD, usually MTX, has been administered without sufficient success . -Adverse effects associated with the biologic agents include the emergence of antinuclear antibodies (ANAs), occasional drug-induced lupuslike syndromes, and infections . - Rarely, demyelinating disorders and bone marrow suppression occur .

10. - Acute and chronic infections, demyelinating disorders, New York Heart Association (NYHA) class III or IV heart failure, and recent malignancies are contraindications for the use of TNF inhibitors . - Patients taking anti-TNF agents must avoid live-virus vaccines to avoid the risk of serious infection . Infliximab - Infliximab , a chimeric monoclonal antibody against TNF-α, is approved for reducing signs and symptoms, inhibiting the progression of structural damage. - This agent binds to cells that express membrane TNF. Infliximab is administered at doses of 3 mg/kg IV at weeks 0, 2, and 6 and then every 4-8 weeks, usually with MTX.

11. Etanercept -Etanercept , a bivalent p75–TNF receptor linked to the Fc portion of human immunoglobulin G -It can be given alone or in combination with MTX. This agent binds lymphotoxin (formerly termed TNF-β) in addition to soluble TNF-α . - The usual dosage is 25 mg SC twice weekly or 50 mg SC weekly, with or without concomitant MTX . Golimumab -Golimumab , a human monoclonal antibody to TNF-α, inhibits TNF-α bioactivity, thereby modulating immune activity in patients with RA . - It is approved for the treatment of adults with moderately to severely active RA, in combination with MTX. -DOSE: 50 mg SC qMonth

12. Certolizumab -Certolizumab is a pegylated anti−TNF-α agent, which results in disruption of the inflammatory process in RA . -Initial dose of 400 mg and 2 subsequent doses of 400 mg at weeks 2 and 4 (given as 2 SC injections of 200 mg), followed by 200 mg every other week . Adalimumab -Adalimumab is indicated to reduce inflammation and inhibit progression of structural damage in moderate to severe RA, alone or in combination with MTX or other nonbiologic DMARDs . This agent is reserved for those who experience an inadequate response to 1 or more DMARDs . Dosage 40 mg SC q2wk