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Premise: traditional disease-modifying antirheumatic drugs are less effective and safe than targeted therapy with biologic response modifiers in rheumatoid arthritis


Multiple traditional disease-modifying antirheumatic drugs (DMARDs), including hydroxychloroquine, gold, penicillamine, sulfasalazine, leflunomide, methotrexate, azathioprine, and cyclosporine, have been approved for use in patients with rheumatoid arthritis. Most patients discontinue these medications by 2 years due to loss of efficacy and/or toxicity. There are currently four biologic response modifiers (BRMs) commercially available: etanercept, infliximab, adalimumab, and anakinra. The question is whether these BRMs have a superior efficacy:tolerability ratio, allowing patients to remain on therapy significantly longer.


To compare clinical trial data of traditional DMARDs and BRMs, alone or in combination, with respect to efficacy and safety.


It is impossible to compare efficacy or safety results of clinical trials of different agents as trial designs, primary endpoints and statistical analyses have changed considerably over the years. The best measure of the effectiveness of a particular medication, therefore, is how long patients remain on therapy that would assume a significant clinical benefit without serious adverse events (AE). Less than 50% of patients treated with traditional DMARDs remain on therapy for 2 years [1]. Combination therapy of DMARDs in patients with established disease does not fare better. Significant AEs that occur with these agents include hematological, hepatic, pulmonary, renal, infectious and mucocutaneous reactions. Each of the BRMs that target tumor necrosis factor alpha have far superior results with respect to continuing therapy: 60% of infliximab patients > 2 years, 52% of patients with etanercept > 4 years and 56% of patients with adalimumab > 5 years [2]. Rare AE that do occur include reactivation of latent tuberculosis and other opportunistic infections, demyelinating disease, congestive heart failure and possibly lymphoma. With proper screening and caution, however, patients should be identified if they are at risk and not treated, thus sparing these AEs. Patients treated with BRMs do not develop the multiorgan adverse events noted with traditional DMARDs


Anti-tumor necrosis factor BRMs appear to have superior efficacy and safety than do traditional DMARDs alone or in combination. For this reason, the use of a BRM should be strongly considered in a patient with rheumatoid arthritis who has not reached maximal efficacy or who develops a significant AE with the use of traditional DMARDs.


  1. Galindo-Rodriguez G, et al: Disappointing longterm results with disease modifying antirheumatic drugs. A practice based study. J Rheumatol. 1999, 26: 2337-2343.

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  2. Fleischmann RM: Safety and efficacy of disease-modifying antirheumatic agents in rheumatoid arthritis and juvenile rheumatoid arthritis. Exp Opin Drug Safety. 2003, 2: 347-365. 10.1517/eods.2.4.347.21415.

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Fleischmann, R. Premise: traditional disease-modifying antirheumatic drugs are less effective and safe than targeted therapy with biologic response modifiers in rheumatoid arthritis. Arthritis Res Ther 5 (Suppl 3), 6 (2003).

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