Background/Purpose: Novel therapeutic concepts in early rheumatoid arthritis (ERA) are aiming for an early intervention and effective control of disease activity reaching remission. Most current guidelines recommend methotrexate (MTX) as the first DMARD even though at least for half of these patients MTX alone is not sufficient to achieve this goal. Currently, the clinical response to the first and probably second DMARD is used to decide further therapeutic approaches. Here we evaluated the autoantigen repertoire as a prospective predictive tool in ERA patients treated with MTX alone or combined with Adalimumab (ADA) in an induction trial (HITHARD study, Detert et al. ARD 2012).

Methods: Luminex-based SeroTag technology was applied to perform large-scale studies in order to define the most prevalent autoantibodies in RA and other connective tissue diseases. 6,000 different human proteins from our huPROT library were incubated with patient sera to screen for autoantibody reactivities and disease or treatment induced alterations using univariate and multivariate statistical algorithms. The DAS28 score was defined as the clinical endpoint, and patients were grouped into those achieving DAS28<2.6 "remission” and “non-remission” in both treatment arms. Autoantibody profiles measured before treatment were then correlated with the status “remission” and “non-remission”.

Results: A previously identified diagnostic panel of six novel antigens allowed to distinguish ERA HITHARD samples from age and sex-matched healthy controls with an AUC=0.94. Comparing pre- and post-treatment samples, a small, but significant reduction (-1.3 fold) of autoantibody reactivities towards two antigens was detected in both treatment arms, even though levels were not normalized compared to healthy controls. A specific autoantibody signature was identified in a subgroup of ERA patients who achieved clinical remission after 24 weeks under ADA/MTX combination therapy. A classification biomarker panel of 5-10 autoantigens appears to be sufficient to identify RA patients who will achieve clinical remission upon ADA/MTX therapy. This panel was independent of anti-citrullinated protein antibody (ACPA) positivity. A different set of up to nine antigens was identified that could predict remission in RA patients upon PLACEBO/MTX therapy.

Conclusion: We identified autoantibody patterns in ERA patients associated with clinical response to an induction therapy and identified two independent marker panels that, if further developed into a screening test, could help to guide future treatment selection for MTX alone or a combined use of MTX/ADA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoantibody-profiles-predict-responsiveness-to-methotrexate-and-anti-tnf-therapy-in-early-rheumatoid-arthritis/