Dmards by fasel rafiq

1. DMARD’s
Presented by : Fasel Rafiq
Group : 3
Course : 6th
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.

4. 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

5. -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

6. 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.

7. 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.

8. 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

9. 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.

10. 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.

11. - 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.

12. 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

13. 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