Disease modified Anti-rheumatic drugs ( DMARD)

BY PROF. AZZA EL-MEDANY DR. OSAMA YOUSIF

General Features & Conditions to use DMARD Low doses are commonly used early in the course of the disease Used when the disease is progressing & causing deformities or damage Used when the inflammatory disease is not responding to NSAIDs Can not repair the existing damage , but prevent further deformity Have no analgesic effects Slow onset their effects take from 6 weeks up to 6 months to be evident

General Clinical Uses Treatment of rheumatic disorders Combination therapies are both safe & effective

Hydroxychloroquine Mechanism of action : Trapping free radicals Suppression of T lymphocyte cells

Pharmacokinetics Rapidly & completely absorbed following oral administration. Penetrates into C.N.S. & Cross the placental barrier Metabolized in liver

Adverse Effects Pruritus GIT upset Headaches Blurred vision Discoloration of nail beds & mucous membranes Irreversible retinal damage

Methotrexate Immunosuppressant drug Used mainly as chemotherapy for cancer treatment Doses of methotrexate as antirheumatic are much lower than those needed in cancer chemotherapy Given once a week

Mechanism of action Inhibition of T-Cells ( cell-mediated immune reactions)

Adverse Effects Nausea Cytopenia Mucosal ulceration Liver cirrhosis Acute pneumonia Mucosal ulceration

Biologic disease modifiers Genetically engineered drugs that are used to modify imbalances of the immune system in autoimmune diseases. (1)Block, or modify the activity of selected cells in the immune system. (2)Blocking action of certain mediators that responsible for inflammatory conditions.

Classification of biologic disease modifiers T-cell modulating drug ( abatacept ) B-cell cytotoxic agent ( rituximab ) Anti-IL-6 blocking agents (Tocilizumab) TNF- α blocking agents ( infliximab)

Tocilizumab IL-6 receptor inhibitor Blocks the activity of IL-6 mediated signaling Half-life is dose dependent (11-13 days ) Given as monthly IV infusion Used as monotherapy in adult with rheumatoid arthritis or in children over 2 years with systemic juvenile arthritis

Cont. In combination with methotrexate or other non biologic anti-rheumatic drugs in patients with active rheumatoid arthritis

Side effects Severe infusion reactions Serious infections ( bacterial, tuberculosis ,fungal Increase cholesterol level Increase liver enzymes Decrease in WBCs Blood tests will be used monthly for increase in cholesterol, liver enzymes & decrease in WBCs

Tumor necrosis factor –α (TNF-α ) blocking agents

Infliximab A chimeric antibody ( 25% mouse, 75% human)

Mechanism of action Binds to human TNF-α resulting in inhibition of macrophage & T cell function

Infliximab Given as IV infusion over at least two hours Half-Life 8-12 days Given every 8 weeks regimen. Elicits up to 62% incidence of human antichimeric antibodies. Concurrent therapy with methotrexate decreases the incidence of human antichimeric antibodies Contraindicated in patients with a history of tuberculosis

Upper respiratory tract infections Activation of latent tuberculosis Pancytopenia Adverse effects Infections Activation of latent tuberculosis Infusion reactions

Comparison between NSAIDs & DMARDs Slow onset of action used in chronic cases when deformity or damage is exciting Arrest progression of the disease Prevent formation of new deformity Rapid onset of action used in acute cases to relief inflammation & pain No effect Can not stop formation of new deformity