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Treatment of Rheumatoid Arthritis: What a Difference a Generation Makes


How safe and effective is combination therapy for rheumatoid arthritis?

How safe and effective is combination therapy for rheumatoid arthritis?

Growing older may not furnish answers to all the questions posed by medicine, but a longer perspective on the therapeutic progress made with rheumatic diseases over the past generation is rewarding. When I was a medical resident in the late 1970s, disease-modifying antirheumatic drugs were not available. Patients with rheumatoid arthritis (RA) were treated with aspirin (often in doses high enough to cause tinnitus and GI bleeding), corticosteroids, and other anti-inflammatory but inefficacious agents (eg, sulfasalazine). The result was terribly crippling joint destruction and a host of other complications, such as osteoporosis, amyloidosis, lung disease, and an early demise.

Then something big happened. A paper published in 1982 discussed methotrexate for the treatment of RA,1 and many more studies followed. Patients with RA who received methotrexate had less joint destruction, less inflammation, and fewer joint replacements.


This month's "Top Paper" takes the treatment of RA a step further with even more gratifying results.2 A group of patients who received methotrexate monotherapy for 2 years (n = 94) was compared with 3 other therapeutic groups: methotrexate for 1 year followed by methotrexate plus etanercept for 1 year (n = 88); combination etanercept/methotrexate for 2 years (n = 108); and etanercept/methotrexate for 1 year followed by etanercept alone the second year (n = 108). End points for the 4 groups included a disease activity score in 28 joints and follow-up to detect the telltale signs of radiographic progression of RA.

Of patients who received methotrexate plus etanercept, 57% achieved remission compared with 35% who received methotrexate alone, the former standard of care. Ninety percent of those patients who received the combination of methotrexate and etanercept had no signs of radiographic progression. No opportunistic infections occurred, and demyelination was also absent in the combination limb.


Patients with RA need to be treated early. Emery and colleagues2 quote studies that have demonstrated a rapid progression of radiographic damage contingent on RA over the first few years of disease activity. Combination therapy, initiated as soon as possible and then sustained, is the best way to approach RA. The tumor necrosis factor group of biologicals has positively augmented the gains made by methotrexate in the treatment of RA. Furthermore, sustained combination therapy did not lead to additional complications.

It has become incumbent on us to diagnose RA as early as possible. Delay in diagnosis, and therefore therapy, is associated with a greater burden of disability. RA causes significant damage early in its course, and that is the definitive time to diagnose and treat it with combination therapy.




Willkens RF, Watson MA. Methotrexate: a perspective of its use in the treatment of rheumatic diseases.

J Lab Clin Med

. 1982;100:314-321.


Emery P, Breedveld F, van der Heijde D, et al; Combination of Methotrexate and Etanercept in Early Rheumatoid Arthritis Trial Group. Two-year clinical and radiographic results with combination etanercept-methotrexate therapy versus monotherapy in early rheumatoid arthritis: a two-year, double-blind, randomized study.

Arthritis Rheum

. 2010;62:674-682.

Dr Rutecki reports that he has no relevant financial relationships to disclose.

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