Table 1.

Traditional DMARDs in clinical application.

Medications	First used	Characteristics	Toxicity
Gold salts (Gold sodium thiomalate and gold sodium thioglucose)	1928	Longest onset of action, administered only by oral or by intramuscular injection. Lack of sustained clinical activity, slow onset of action, cost, poor long-term compliance.	High incidence of toxicity requiring drug discontinuation: mucocutaneous reations, proteinuria and cytopenias.
Sulphasalazine	1938	the first DMARD specifically synthesized for the treatment of RA. Low cost.	GI-related complications, neutropenia, cytopenias.
Antimalarials (Chloroquine, hydroxychloroquine)	1940s	Less effective than other DMARDs, but also less toxic, readily absorbed orally, extended serum half-lives due to tissue depot effects.	Rare but potential renal toxicity
Methotrexate	1950s	Gold-standard therapy, sustained long-term action, high tolerability, low cost, antimetabolite and antifolate drug.	Hepatitis and cirrhosis, interstitial pneumonitis, cytopenias.
Azathioprine	1960s	An immunosuppressant used to treat severe rheumatoid arthritis.	Vomiting, diarrhea, muscle aches. Increasing risk of developing certain types of cancer, especially skin cancer and lymphoma.
D-penicillamine	1960s	A metabolite of penicillin. Used to treat active rheumatoid arthritis that has not responded to other measures.	Rashes, loss of appetite, nausea, abdominal pain, and loss of the sense of taste. bone marrow suppression and serious kidney disease
Cyclosporine A	1980s	Calcineurin inhibitor. Third-line drug in RA therapy.	Renal insufficiency, anemia, hypertension
Leflunomide	1988	Inhibits de novo pyrimidine synthesis, similar efficacy with methotrexate and sulphasalazine.	Most important serious adverse reaction is hepatotoxicity
Minocycline	1990s	A member of the broad spectrum tetracycline antibiotics, mildly beneficial.	Autoimmune syndromes, headaches and a graying skin pigmentation.