AB0469 Can Anti-TNF-Induced Autoantibody Conversion be Reversed by Switching to Abatacept Therapy in Patients with RA on Background MTX?
Authors: M.H. Buch, A. Johnsen, D.A. Wong, M. Schiff
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Anti-TNF therapy is associated with the induction of antinuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies in patients (pts) with RA.<sup>1,2</sup> The effect of subsequent biologic therapy on such pts has not been explored. <h3>Objectives</h3> To compare the development of ANA and anti-dsDNA antibodies during treatment with abatacept (ABA) and anti-TNFs in the ATTEST and AMPLE trials, and to evaluate the effect of switching to ABA in pts with RA who developed anti-TNF-induced ANA/anti-dsDNA antibodies in the ATTEST trial. <h3>Methods</h3> In the 1-year double-blind (DB) ATTEST trial, pts were randomized to IV ABA (∼10 mg/kg every 4 weeks), infliximab (IFX; 3 mg/kg every 8 weeks) or placebo, all on background MTX. At Mth 6, placebo-treated pts were reallocated to ABA (blinding maintained); pts initially randomized to ABA or IFX continued treatment. Pts completing the 1-year DB period were eligible to receive ABA in an open-label long-term extension (OLE). In the head-to-head AMPLE trial, pts were randomized to SC ABA (125 mg weekly) or SC adalimumab (ADA; 40 mg biweekly), on background MTX for 2 years. Pts in both trials were biologic naïve, with an inadequate response to prior MTX and active RA. Blood samples were collected for the measurement of ANA and anti-dsDNA at baseline, Mth 6, Year 1 (end of DB period) and Year 2 (OLE) in the ATTEST trial, and at baseline, Year 1 and Year 2 in the AMPLE trial. <h3>Results</h3> In the ATTEST DB period, 156 pts received IV ABA and 165 received IFX; 132 ABA- and 136 IFX-treated pts continued into the OLE and received IV ABA. In AMPLE, 318 pts received SC ABA and 328 received ADA. At baseline in the ATTEST trial, 69 pts on active treatment (32 IV ABA, 37 IFX) were ANA positive and 26 pts (11 IV ABA, 15 IFX) were anti-dsDNA positive. In the AMPLE study, the respective numbers at baseline were: 166 ANA-positive pts (72 SC ABA, 94 ADA) and 6 anti-dsDNA-positive pts (1 SC ABA, 5 ADA). The % of pts with seroconversion for ANA or anti-dsDNA in the active treatment arms of each trial are shown in the Table. In both ATTEST and AMPLE, a higher % of pts receiving anti-TNF therapy seroconverted from baseline negative to positive during Year 1 of treatment, compared with those receiving ABA. This difference in autoantibody induction for anti-TNF versus ABA continued during the second year of AMPLE. In ATTEST, 48.5% (ANA) and 48.3% (anti-dsDNA) of IFX-treated pts who entered the OLE seroconverted from baseline ANA or anti-dsDNA negative to positive at Year 1; this dropped to 22.4% and 13.3%, respectively, at Year 2 after switching to ABA. The % of pts who converted from baseline positive to negative status increased from 12.1% in the IFX group to 20.6% on switching to ABA (Table). <h3>Conclusions</h3> In the ATTEST trial, switching from infliximab to abatacept seemed to reverse the autoantibody induction observed with anti-TNF treatment. Anti-TNF therapy was associated with greater autoantibody (ANA and anti-dsDNA) induction than abatacept in the ATTEST and AMPLE trials. These data provide additional insights into differences in the mechanism of action of anti-TNFs and abatacept, and imply an effect of T-cell co-stimulation blockade on B-cell function and autoantibody production. <h3>References</h3> Charles PJ, et al. Arthritis Rheum 2000;43:2383–90. Eriksson C, et al. Ann Rheum Dis 2005;64:403–7. <h3>Disclosure of Interest</h3> M. H. Buch Grant/research support from: Pfizer, Bristol-Myers Squibb, Speakers bureau: AbbVie, Bristol-Myers Squibb, Roche-Chugai, Pfizer, A. Johnsen Employee of: Bristol-Myers Squibb, D. A. Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Schiff Grant/research support from: UCB, Consultant for: AbbVie, Amgen, Antares, Bristol-Myers Squibb, Eli Lilly, Horizon, Johnson and Johnson, Novartis, Novo Nordisk, Pfizer, Roche, UCB, Speakers bureau: AbbVie