Combined B cell/T cell therapy as novel approach for the re-induction of humoral immune-tolerance.

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Despite considerable efforts and success in the development of anti-inflammatory drugs, there is yet no curative treatment for rheumatoid arthritis (RA). In the proposed investigator initiated trial we aim to sequentially combine a B cell-targeted therapy and a T cell-targeted therapy to induce a state of clinical remission as well as to re-establish immune tolerance in autoantibody-positive RA patients. ACPA-positive active RA patients will receive rituximab, followed by a treatment with abatacept or placebo. Primary outcome is the change in autoantibody (ACPA) levels, while secondary outcomes will be the change ACPA glycosylation and in B cell and T cell responses as well as the effects on clinical disease activity.