Rituximab dissociates the tight link between disease activity and joint damage in rheumatoid arthritis patients

Background/objective Progression of joint damage is linked to disease activity. This link is dissociated upon treatment with tumour necrosis factor (TNF)- or IL-6-inhibitors plus methotrexate (MTX). It is hitherto unknown if this may also be true for therapies targeting B-cells. We thus evaluated if rituximab (RTX) therapy inhibits joint damage irrespective of its effects on disease activity. Methods We used a random 90% sample of data from two arms of the IMAGE trial comprising patients with active early rheumatoid arthritis (RA) receiving MTX (n = 188) or MTX + RTX 1000 mg (n = 204). Patients were divided into low, moderate and high disease activity at one year of treatment by simplified disease activity index (low disease activity (LDA), moderate disease activity (MDA), high disease activity (HDA)), or by swollen joint count (SJC) or C reactive protein (CRP) tertiles. Progression of damage by the Genant modified total Sharp score (TGSS) was compared between therapies (Kruskal-Wallis, Wilcoxon tests) for each of these subgroups. Results In patients treated with MTX, 1-year progression of TGSS In LDA, MDA and HDA was 0.40 +/- 0.88, 1.04 +/- 1.73, and 1.31 +/- 3.02, respectively. In contrast, on RTX + MTX, TGSS progression was 0.38 +/- 1.07, 0.39 +/- 1.28, and -0.05 +/- 0.44, respectively (for MDA and HDA the progression of TGSS was significantly lower in the combined group than in the MTX group: p = 0.003 and p = 0.05, respectively). Additional analyses (tertiles of SJC, CRP, and matching for disease activity) confirmed the primary analysis. Conclusions In early RA, progression of joint damage increases with increasing disease activity on MTX. RTX plus MTX retards damage independently of its effects on disease activity, since even in HDA destruction is halted, contrasting MTX monotherapy. This indicates that beyond cytokine blockade (TNF- and IL-6 inhibitors), also cell-directed therapy (anti-CD20 antibody) conveys profound anti-destructive effects and dissociates the link between disease activity and joint damage.