Should We Redefine Treatment Targets in Rheumatoid Arthritis? Low Disease Activity Is Sufficiently Strict for Patients Who Are Anticitrullinated Protein Antibody-negative

Abstract

Clinical remission currently is the treatment target for all patients with rheumatoid arthritis (RA). At the same level of inflammation, the prognosis regarding joint damage is believed to be different for anticitrullinated protein antibody (ACPA)-negative and ACPA-positive patients. Our objective was to show the difference in prognosis at similar disease activity levels, and to illustrate how this could be translated to differentiation of treatment targets. Data were used from the Nijmegen Early RA Cohort. The relation between the time-averaged disease activity level (by Disease Activity Score; DAS) and joint damage progression over 3 years was analyzed, separately for ACPA-negative and ACPA-positive patients. Joint damage was assessed as change in Ratingen score, and dichotomized as occurrence of erosions in joints that were unaffected at baseline. Linear and logistic multivariable regression models were used. The regression coefficient of DAS on change in Ratingen score was 3.9 (p < 0.001) for ACPA-negative and 4.7 (p < 0.001) for ACPA-positive patients, showing less joint damage progression at the same disease activity level in ACPA-negative patients. This difference became greater with increasing disease activity. The probability for erosions in joints unaffected at baseline was 0.35 in ACPA-negative patients when time-averaged DAS was < 2.4 versus 0.80 in ACPA-positive patients. At the same level of inflammation, ACPA-negative patients have less joint damage and lower probability for damage in newly affected joints than ACPA-positive patients. Low disease activity might be a sufficiently strict treatment target for ACPA-negative patients to prevent progression of joint damage.