DMARDs.(Disease Modifying Anti-Rheumatoid Drugs)

-25% recover completely
-continue more or less normal life with drug therapy.

Drug Therapy.

.Analgesia and NSAIDs
                                     -mainly for symptoms control.

.Cortocosteroids.
                          -slows down the progress of the disease.(immunosupressants)
                          -intra-articular injections and i.m. depot injections.

.Disease Modifying Anti-Rheumatoid Drugs.(DMARDs)

Traditional DMARDs.
                       
 "Most Sufferers Can Get Appropriate Pain Control...Lol ".

M-methotrexate
S-sulfasalazine
C-ciclosporin
G-gold
A-azathioprine.
P-penicillamine
C-hydroxyChloroquine
L-leflunomide


Biological DMARDs. 

-genetically  engineered drugs – meaning that human genes that normally guide the production of these natural human immune proteins (i.e., an antibody to TNF) are used in non-human cell cultures to produce large amounts of a biologic drug.

-In these diseases, TNF or IL-1 act to increase inflammation, similar to the effect of gasoline on a fire.
-However, in rheumatoid arthritis TNF or IL-1 (the gasoline) acts to excite the inflamed joint (the fire).

-are very expensive

-so, they are used after at least 2 traditional DMARDs usually methotrexate and sulfasalazine.

1.TNF-alpha inhibitors.
                 -etanercept
                                  -fully humanized p75 TNF-alphareceptor IgG1.
                                  -25 mg 2 weekly or 50mg weekly, s.c
                                 -Given S.C  and self-administration.
                                  -65% of patients respond well.
                 -adalimumab
                                  -s.c 40mg alternate week
                                  -fully humanized monoclonal antibody against TNF-alpha given along with methotrexate.
                  -infliximab
                                 -i.v. 3-10mg/kg every 4-8 weeks.
                                  -a monoclonal antibody against TNF-alpha
                                  -co-prescribed with methotrexate
                                  -given intravenously.

*These drugs slow or halt erosion formation upto 70% of patients with RA and produce healing in few.
*Chances of secondary failure, 50% with infliximab and less with etanercept and adalimumab.

Side Effects:
                -Increased tumour development is controversial.
                -ANA positive in few--->SLE, Leucocytoclastic vasculities, extracutaneous involvement or sinterstitial lung disease
                -Reactivation of old TB, therefore pre-treatment chest x-ray recommended.
                -increased risk of infection, so close monitoring required.

2.Cytokine IL-1 inhibitor.
                                        -Anakinra
                                                      -a human recombinant IL-1 receptor antagonist.
                                                      -used along with methotrexate
                                                      -used after anti-TNF agents failure.

3.Others.
             1.Rituximab
                               - a monoclonal Ab
                               -lysis of CD-positive B cells.
             2.Abatacept
                               -modulates T cells activation.
             3.Tocilizumab
                                -Anti-IL-6 receptor (clinically in trials now)

Drugs Used Less Commonly.

            1.Gold- sodium aurothiomalate by deep I.M. injection
            2.Hydroxychloroquine.- anti-malarial
                                               -200-400mg daily alone in mild disease or as an adjunct to DMARDs.
                                               -retinopathy is side effect.
           3.Penicillamine-125g daily for 1 month and 500-750g daily before food for at least 3 months before improvement occurs.
                                 -if proteinuria exceeds >2g/24h, it should be stopped.
                                 -SLE and myasthenia gravis like syndrome occurs.
           4.Azathioprine- max. dose of 2.5mg/kg and cyclophosphamide 1-2mg/kg usually when DMARDs are ineffective.
            5.Ciclosporin
                               -2.5-4mg.kg
                               -used for active RA.
                               -s.e- hypertension and rise in creatinine level.