Relative versus absolute goals of therapies for RA: ACR 20 or ACR 50 responses versus target values for "near remission" of DAS or single measures.

Therapies for rheumatoid arthritis (RA) may be assessed according to relative levels of measures to compare efficacy to another therapy or to a placebo, as in the American College of Rheumatology (ACR) 20%, 50%, or 70% (ACR 20 ACR 50 and ACR 70) responses, or by absolute levels of measures, as in disease activity scores (DAS), ACR criteria for remission, or "target values" of specific measures. Regulatory considerations have emphasized primarily relative comparisons to a placebo or standard therapy, derived in part from the weak efficacy of traditional disease modifying anti-rheumatic drugs (DMARDs). While improvement compared to placebo certainly indicates efficacy, it is of concern that measures of inflammatory activity, such as swollen joints and the erythrocyte sedimentation rate (ESR), may be stable or improved over periods of 5-10 years, while measures of damage, such as joint deformity and radiographic changes, may progress over the same period in the same patients. These findings suggest that improvement at a level of 20% or 50% may deter but not prevent severe long-term outcomes of radiographic progression, functional declines, work disability, and premature mortality, seen in most patients until the middle 1990s. Outcomes appear to be improved at this time, associated with aggressive treatment strategies and more powerful therapies, including biologic agents. In the Finnish Rheumatoid Arthritis Combination Therapy Trial (FinRACo), no patient who was in remission after 6 months was receiving work disability payments 4 1/2 years later, compared to 22% of patients who had ACR 20 or 50 responses and 54% of patients who did not have ACR 20 responses after 6 months who were all receiving work disability payments after 5 years. These findings suggest that absolute targets, including remission, may be realistic contemporary goals, with aggressive treatment strategies and more effective DMARDs and biologic agents.