Drug used in treatment of rheumatoid arthritis that acts by inhibition of T-cell proliferation?

Ans. d (Leflunomide) (Ref. H - 16th ed. Table 295-14 & p. 1968).# LEFLUNOMIDE metabolized to an active metabolite that acts to inhibit dihydroorotate dehydrogenase, an essential enzyme in the pyrimidine biosynthetic pathway.# Its predominant action is to inhibit the proliferation of T lymphocytes.# It is as effective as methotrexate.# Leflunomide can be given alone or with methotrexate.# The major side effect is the associated increase in liver function enzymes.DMARDs# May slow or reverse joint damage# Indicated for the treatment of RA when an ati-inflammatory therapy insufficient to control patient's symptomatology# DMARDs usually do not show benefit for 6-8 weeks or longer; so, bridging therapy# DMARDs have severe and potentially fatal side effectsHydrochloroquine# Stabilizes lysosomes, chemotaxis# Also an antimalarialOphthalmic abnormalities, dermatologic reactions hematotoxicity, GI reactionsMethotrexate# Inhibits dihydrofolate reductase, immunosuppressant# Also an antineoplasticHemotoxicity, ulcerative stomatitis, renaltoxicity, elevated LFTsSulfasalazine# Metabolized to 5-aminosalicylic acid (5 ASA) and sulfapyridine; parent drug and/or metabolites have anti-inflammatory and/or immunomodulatory properties# Used in inflammatory bowel diseaseRash, GI distress, headache, hematotoxicityGold compounds# Macrophage and lysosomal functionsDermatitis, hematotoxicity, nephrotoxicityAzathioprine# Purine metabolism and nucleic acid synthesis# ImmunosuppressantHematologic, GI disturbance, secondary infection, increased risk of neoplasiaPenicillamine# T-cell activity and rheumatoid factor# Also a chelating agentGI disturbances, proteinuria, bone marrow suppression, neurotoxicityEtanerceptBinds TNFInjection site reactionsLeflunomideInhibits cell proliferation and anti-inflammatoryHepatotoxicity, immunosuppression, GI disturbance, alopecia, rash,teratogenInfliximab# Monoclonal antibody to TNF-a# Also used in inflammatory bowel diseaseInfusion reactions, infections, activation of latent TB Immunomodulatory Agents1Recombinant TNF-receptor-Ig fusion protein (etanercept)# Inhibit TNF-alpha# FDA approved for rheumatoid arthritis, juvenile rheumatoid arthritis, psoriasis2Anti-IL-6 monoclonal antibody# Inhibit IL-6, Tested in phase 1 trial in rheumatoid arthritis3Inferferon-ss# Inhibit IL-1, decrease synovial T cells# In trials for use in rheumatoid arthritis4Interferon-gamma# Induce monocyte/macrophage activation Agents# Effective in treating monocyte/macrophage phagocytic defects in chronic granulomatous disease.5IL-11# Inhibit TNF-a and IL-1 production# In trials for Crohn's colitis6IL-12# Stimulate anti-tumor and anti-viral or bacterial cytotoxic T lymphocyte responses# Trials underway for use in cancer patients# Trials planned in humans to prevent/treat severe infections7Anakinra # Inhibit IL-la and -ss FDA approved for rheumatoid arthritis. Anakinra is a recombinant IL2-1 receptor antagonist that competitively blocks the binding of IL-1ss and IL-la to the IL-1 receptor and thereby inhibits the activity of these two related proinflammatory cytokines.# Anakinra has been shown to improve the signs and symptoms of RA, to decrease disability, and to slow progression of articular damage associated radiographically.8Etanercept# A recombinant fusion protein consisting of two soluble TNF p75 receptor moieties linked to the Fc portion of human IgGl; it binds TNF-alpha molecules and also inhibits lymphotoxin- alpha.# Etanercept is approved for the treatment of rheumatoid arthritis, juvenile chronic arthritis, and psoriatic arthritis and ankylosing spondylitis.# While etanercept is ineffective for treatment of ulcerative colitis, it is being used in many rheumatic syndromes such as scleroderma, Wegener's granulomatosis, giant cell arteritis, and sarcoidosis.9Adalimumab# Adalimumab is a fully humanized antibody (IgGl) used in treatment of rheumatoid arthritis.# A recombinant human anti-TNF monoclonal antibody.# This compound complexes with soluble TNF-a and prevents its interaction with p55 and p75 cell surface receptors.# This results in down-regulation of macrophage and T cell function.# The compound is indicated for the treatment of rheumatoid arthritis and decreases the rate of formation of new erosions.# It is effective both as monotherapy and in combination with methotrexate.# The usual dose is 40 mg every other week, though increased responses may be evident at higher dosages.# Adalimumab is presently being tested in psoriasis, psoriatic arthritis, ankylosing spondylitis, and juvenile chronic arthritis.10Infliximab# A chimeric (25% mouse, 75% human) monoclonal antibody that binds with high affinity to soluble and possibly membrane-bound TNF-a.# Its mechanism of action probably is the same as that of Adalimumab.# Infliximab is effective in rheumatoid arthritis and ulcerative colitis and is being used in other diseases, including psoriasis, psoriatic arthritis, juvenile chronic arthritis, Wegener's granulomatosis, giant cell arteritis, and sarcoidosis.# Infliximab, etanercept, and adalimumab are new biologic agents that bind TNF-a, a proinflammatory cytokine. # Infliximab is currently approved for use in Crohn's disease of the colon and in rheumatoid arthritis.11 Leflunomide# Inhibits T cell proliferation and production of autoantibodies by B cells.# Effects include increases of interleukin-10 receptor mRNA, decreased interleukin-8 receptor type A mRNA, and decreased TNF-a-dependent NF-B activation.# Used in treatment of RA.RITUXIMAB (anti-CD20 antibody)# It is an anti-CD20 antibody that also has clinical activity: CLL, NHL (relapsed or refractory low-grade or follicular B cell non-Hodgkin's lymphoma.) and Ca colon.# Rituximab may be used in treatment of:- B cell chronic lymphoid leukemia,- Follicular lymphoma,- Mantle cell lymphoma,- Cold agglutinin disease,- Idiopathic thrombocytopenic purpura, and- Waldenstrom's macroglobulinemia- Rituximab is also used with methotrexate to treat moderate-to-severe forms of rheumatoid arthritis.