Inverting the therapeutic pyramid: Observations and recommendations on new directions in rheumatoid arthritis therapy based on the author's experience

In evaluating current therapy for rheumatoid arthritis (RA), it is increasingly being recognized that sequential single-drug treatment, as exemplified by the traditional therapeutic pyramid, is often too little, too late, and ineffective in preventing disease progression or joint damage in patients with “at-risk,” aggressive synovitis or what might be called type 2 RA. Designation of drugs as either antiinflammatory or disease-modifying is not supported by the author's experience. Evidence exists that prevention of joint damage correlates best with control of clinical and laboratory measures of inflammation, regardless of the medication used. The earlier and more effective the control of the inflammation, the better the patient response. Until a major breakthrough occurs, the author recommends that patients with aggressive RA be treated with a combination of fast-acting and slow-acting medications to achieve early control and then “bridge down” to a simplified maintenance program. Retrospective observation by the author of 54 patients with early, intermediate, and late disease treated with combinations of prednisone, methotrexate, auranofin, hydroxychloroquine, and azathioprine showed maximum response in patients with disease duration of less than 2 years, minimal toxicity, and lack of erosions in patients with control of inflammation. Twelve patients with inflammation not initially suppressed by prednisone and methotrexate had improved control with additional drugs in combination, including auranofin, hydroxychloroquine, and azathioprine. After inflammation was controlled, reduction of prednisone and methotrexate doses was possible in 60% of patients, primarily those with early disease. The goal of this therapeutic model is to control inflammation before joint damage occurs and progressively simplify the cost and complexity of therapy in contrast to the current pyramidal approach.