THU0109 Autoantibody profiling for response to baricitinib in patients with rheumatoid arthritis and no or limited exposure to methotrexate
Authors: L. Martinez Gamboa, H. Bang, M. Issa, S. Zuckerman, A. Cardoso, T. Holzkaemper, F. De Leonardis, I. de la Torre, Y. Tanaka, E. Feist
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Posttranslational antigen modification plays a role in the pathogenesis of rheumatoid arthritis (RA). The associated autoantibodies are considered unfavourable prognostic factors with respect to disease severity and radiographic outcome. Limited information is available for different serotypes and prediction of treatment response to Janus kinase inhibitors including baricitinib (BARI). <h3>Objectives</h3> To clarify whether fine profiling of baseline autoantibodies against different modified isoforms of vimentin correlate with clinical or radiographic outcome in patients (pts) with active RA and no or limited prior DMARD treatment who initiate treatment with BARI. <h3>Methods</h3> Baseline sera samples from DMARD-naïve pts participating in the randomised, active comparator-controlled Ph3 trial RA-BEGIN<sup>1</sup> [methotrexate (MTX) n=210, BARI 4 mg (mono) n=159 and BARI 4-mg+MTX (combo) n=215] were investigated for autoantibody class (IgG, IgM and IgA) reactivity towards vimentin (V), modified by citrullination (MCV), carbamylation (Carb) or acetylation (Acct), using enzyme-linked immunosorbent assay. Pts were stratified according to negative (&lt;20 U/ml), low-positive (20–60 U/ml) and high-positive (&gt;60 U/ml, 3-fold above the ULN) antibody titre or with respect to the antibody titre tertiles. Change in clinical outcomes (DAS28-CRP, CDAI) and radiographic progression (modified Total Sharp Score) were analysed from baseline to Week 24 using modified last observation carried forward and linear extrapolation, respectively, by baseline autoantibody subclass and titre. <h3>Results</h3> Comparison of least squares mean difference in clinical scores showed more consistent improvement in pts treated with BARI combo vs MTX irrespective of baseline autoantibody subclass and titre. In general, pts with low-titre anti-CarbV, AcctV and MCV subclass antibodies showed numerically less improvement in most of the analyses under BARI mono vs MTX compared to BARI combo vs MTX although for anti-CarbV subclass seronegative pts, no significant differences were found in the clinical response between BARI mono vs MTX. Furthermore, anti-MCV IgA and IgM as well as anti-CarbV IgA negative status was also associated with significant reduction of radiographic progression in pts treated with BARI combo vs MTX. For seropositive pts, response to treatment with BARI mono or combination therapy was higher in pts with highest titres of anti-MCV and anti-CarbV. However, a significant difference with respect to radiographic progression was detectable only for BARI combo vs MTX. By stratifying pts according to their antibody profile, these observed radiographic differences were achieved in the anti-MCV and anti-CarbV IgG high-positive as well as anti-CarbV IgM low-positive pts. <h3>Conclusions</h3> In these exploratory analyses, seropositive pts with high titres of anti-MCV and anti-CarbV at baseline showed better responses to BARI mono or combo vs MTX for composite scores, and to BARI combo in structural progression outcomes. <h3>Reference</h3> [1] Fleischmann R, et al. Arthritis Rheumatol2017;69(3):506–517. <h3>Disclosure of Interest</h3> L. Martinez Gamboa Grant/research support from: Eli Lilly and Company, H. Bang: None declared, M. Issa Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. Zuckerman Employee of: Former employee of Eli Lilly and Company, A. Cardoso Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, T. Holzkaemper Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, F. De Leonardis Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, I. de la Torre Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, Abbvie, MSD, Daiichi-Sankyo, Pfizer, Kyowa- Kirin, Eisai, Ono, Speakers bureau: Daiichi-Sankyo, Astellas, Pfizer, Mitsubishi-Tanabe, Bristol-Myers, Chugai, YL Biologics, Eli Lilly and Company, Sanofi, Janssen, UCB, E. Feist Grant/research support from: Eli Lilly and Company, Novartis, Roche, BMS, Consultant for: Eli Lilly and Company, Novartis, Roche, Pfizer, Abbvie, BMS, MSD, Sanofi, Speakers bureau: Eli Lilly and Company, Novartis, Roche, Pfizer, Abbvie, BMS, MSD, Sanofi