gms | German Medical Science

Introduction: Anti-TNF therapy for RA is associated with antinuclear (ANAs) and anti-double-stranded DNA (anti-dsDNA) autoantibodies [1], [2]. The effect of biologics on autoantibody-positive patients is unknown. We explored ANA and anti-dsDNA antibody development during abatacept (ABA) and anti-TNF treatment (ATTEST/AMPLE trials) and effects of switching to ABA in patients with ANA/anti-dsDNA (ATTEST).

Methods: All patients had active RA, were biologic naïve and MTX inadequate responders. ATTEST: patients were randomized to IV ABA (≈10mg/kg q4w), infliximab (IFX; 3mg/kg q8w) or placebo, on background MTX. At Month 6, placebo-treated patients started ABA (blinding maintained); ABA- and IFX-treated patients continued treatment. Patients completing the 1-year DB period were eligible to receive ABA (open-label long-term extension [OLE]). AMPLE (2-year head-to-head trial): patients were randomized to SC ABA (125mg weekly) or SC adalimumab (ADA; 40mg biweekly), on background MTX. Serum ANA and anti-dsDNA were measured at baseline, Month 6, Year 1 and 2 in ATTEST, and at baseline, Year 1 and 2 in AMPLE.

Results: In the ATTEST DB period, 156 patients received IV ABA and 165 received IFX; 132 and 136 patients received IV ABA in the OLE, respectively. In AMPLE, 318 patients received SC ABA and 328 received ADA. At baseline in ATTEST, 69 patients (32 IV ABA/37 IFX) were ANA+ and 26 (11 IV ABA/15 IFX) were anti-dsDNA+; AMPLE: 166 were ANA+ (72 SC ABA/94 ADA) and 6 anti-dsDNA+ (1 SC ABA/5 ADA). In both studies, a higher percentage of patients seroconverted (negative–positive, baseline–Year 1) with anti-TNFs versus ABA (Table 1 [Tab. 1]); this difference continued during AMPLE Year 2. In ATTEST, 48.5% (ANA) and 48.3% (anti-dsDNA) of IFX-treated patients who entered the OLE seroconverted (negative–positive, baseline–Year 1), falling to 22.4% and 13.3%, respectively, at Year 2 after switching to ABA. The percentage of patients who seroreverted (baseline positive–negative) increased from 12.1% to 20.6% on switching from IFX to ABA (Table 1 [Tab. 1]).

Conclusion: In ATTEST, switching from infliximab to abatacept seemed to reverse autoantibody induction observed with anti-TNF treatment. In both trials, anti-TNF therapy was associated with greater autoantibody induction than abatacept. These data imply an effect of T-cell co-stimulation blockade on B-cell function and autoantibody production.

Note: This abstract was first presented at the EULAR Congress, 10–13 June 2015, Rome, Italy (AB0469) and published in the corresponding supplement of Ann Rheum Dis.