A personalized medicine approach to biologic treatment of rheumatoid arthritis: a preliminary treatment algorithm

Abstract

RA is a syndrome consisting of different pathogenetic subsets in which distinct molecular mechanisms may drive common final pathways. Recent work has provided proof of principle that biomarkers may be identified predictive of the response to targeted therapy. Based on new insights, an initial treatment algorithm is presented that may be used to guide treatment decisions in patients who have failed one TNF inhibitor. Key questions in this algorithm relate to the question whether the patient is a primary vs a secondary non-responder to TNF blockade and whether the patient is RF and/or anti-citrullinated peptide antibody positive. This preliminary algorithm may contribute to more cost-effective treatment of RA, and provides the basis for more extensive algorithms when additional data become available.

Fig. 1

ACR responses typically observed 24 weeks after initiation of treatment with any of the biologics used for the treatment of patients with RA who have failed MTX. Although the results on the group level may be comparable, individual patients who fail one mechanism of action are not necessarily the same as those failing a different mechanism of action.

Fig. 2

Clinical signs and symptoms of RA are associated with macrophage infiltration and activation. Different pathogenetic mechanisms may drive this common final pathway. Successful treatment of RA results in decreased accumulation of synovial macrophages associated with clinical improvement, independent of the specific mechanism of action. Mø: macrophage; FLS: fibroblast-like synoviocyte.

Fig. 3

Treatment algorithm for patients with RA who have failed conventional treatment with DMARDs and treatment with one TNF inhibitor. Treatment decisions are influenced by distinguishing between primary non-responders (here defined as no clinical response 12–16 weeks after initiation of anti-TNF treatment) and secondary non-responders (here defined as initial clinical improvement followed by loss of response ≥24 weeks after initiation of anti-TNF treatment) as well as positivity for RF and ACPAs. Switching to a different mechanism of action is recommended if a patient does not respond clinically to the first course of rituximab.