Who would have thought 10 years or even 5 years ago that our current success in treating rheumatoid arthritis (RA) could have an adverse effect on future drug development? Even a decade ago this question would have been considered moot owing to the limited number of effective treatments available then for RA. Since that time therapeutic advances have made a substantial impact on the ability to control this disease.

PROGRESS OVER THE PAST 20 YEARS

To understand the problems that we now face in drug development in RA it is important to look back and see how far we have progressed over the past 20 years. In 1985 many rheumatologists considered RA to be a slowly progressing disease, one in which radiographic damage required years to become evident. The approach to treatment was the “pyramid” concept: a sedate escalation from aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), then to corticosteroids, and finally, the eventual introduction of slow acting antirheumatic drugs, which included antimalarial agents, gold salts, and d-penicillamine.

The year 1985 was a watershed year for therapeutics in RA: the first placebo controlled trials were published, which validated the effectiveness of low dose weekly methotrexate (MTX) in RA.^1–,³ Twenty years later MTX has become the “standard of care”, both as a monotherapy for RA and as the “anchor” drug in combination treatments. What has changed most over the past two decades is an appreciation of the need for early and aggressive intervention with disease modifying treatments. Seminal studies, primarily from Europe, show that disease modifying treatments, regardless of the type, lead to a better outcome than NSAIDs or low dose prednisone alone in improving clinical disease activity.^4–,⁶ Studies have established that control of synovitis with drug treatment, particularly combination treatments, not only improves …