Treatment options for rheumatoid arthritis: celecoxib, leflunomide, etanercept, and infliximab.
OBJECTIVE
To review new pharmacologic agents approved for use in the management of rheumatoid arthritis (RA).


METHODS
A MEDLINE search (1966-January 2000) was conducted to identify English-language literature available on the pharmacotherapy of RA, focusing on celecoxib, leflunomide, etanercept, and infliximab. These articles, relevant abstracts, and data provided by the manufacturers were used to collect pertinent data.


METHODS
All controlled and uncontrolled trials were reviewed.


METHODS
Agents were reviewed with regard to mechanism of action, efficacy, drug interactions, pharmacokinetics, dosing, precautions/contraindications, adverse effects, and cost.


RESULTS
Traditional pharmacologic treatments for RA have been limited by toxicity, loss of efficacy, or both. Increasing discoveries into the mechanisms of inflammation in RA have led to the development of new agents in hopes of addressing these limitations. With the development of celecoxib, a selective cyclooxygenase-2 inhibitor, the potential exists to minimize the gastrotoxicity associated with nonsteroidal antiinflammatory drugs. Leflunomide has been shown to be equal to or less efficacious than methotrexate, and may be beneficial as a second-line disease-modifying antirheumatic drug (DMARD). The biologic response modifiers, etanercept and infliximab, are alternatives that have shown benefit alone or in combination with methotrexate. However, they should be reserved for patients who fail to respond to DMARD therapy. Further studies should be conducted to evaluate the long-term safety and efficacy of these agents as well as their role in combination therapy.


CONCLUSIONS
Celecoxib, leflunomide, etanercept, and infliximab are the newest agents approved for RA. Clinical trials have shown that these agents are beneficial in the treatment of RA; however, long-term safety and efficacy data are lacking.
Luong
B T
BT
Department of Pharmacy Practice, Medical University of South Carolina, Charleston 29425, USA.
Chong
B S
BS
Lowder
D M
DM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068579:Celecoxib; D004347:Drug Interactions; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D007555:Isoxazoles / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077339:Leflunomide; D008297:Male; D011720:Pyrazoles; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007555:Isoxazoles; D011720:Pyrazoles; D018124:Receptors, Tumor Necrosis Factor; D013449:Sulfonamides; D000069285:Infliximab; D000077339:Leflunomide; D000068579:Celecoxib; D000068800:Etanercept