D.A. Wong

Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period

Objectives To evaluate clinical remission with subcutaneous abatacept plus methotrexate (MTX) and abatacept monotherapy at 12 months in patients with early rheumatoid arthritis (RA), and maintenance of remission following the rapid withdrawal of all RA treatment. Methods In the Assessing Very Early Rheumatoid arthritis Treatment phase 3b trial, patients with early active RA were randomised to double-blind, weekly, subcutaneous abatacept 125 mg plus MTX, abatacept 125 mg monotherapy, or MTX for 12 months. Patients with low disease activity (Disease Activity Score (DAS)28 (C reactive protein (CRP)) <3.2) at month 12 entered a 12-month period of withdrawal of all RA therapy. The coprimary endpoints were the proportion of patients with DAS28 (CRP) <2.6 at month 12 and both months 12 and 18, for abatacept plus MTX versus MTX. Results Patients had <2 years of RA symptoms, DAS28 (CRP) ≥3.2, anticitrullinated peptide-2 antibody positivity and 95.2% were rheumatoid factor positive. For abatacept plus MTX versus MTX, DAS28 (CRP) <2.6 was achieved in 60.9% versus 45.2% (p=0.010) at 12 months, and following treatment withdrawal, in 14.8% versus 7.8% (p=0.045) at both 12 and 18 months. DAS28 (CRP) <2.6 was achieved for abatacept monotherapy in 42.5% (month 12) and 12.4% (both months 12 and 18). Both abatacept arms had a safety profile comparable with MTX alone. Conclusions Abatacept plus MTX demonstrated robust efficacy compared with MTX alone in early RA, with a good safety profile. The achievement of sustained remission following withdrawal of all RA therapy suggests an effect of abatacepts mechanism on autoimmune processes. Trial registration number NCT01142726.

Sustained improvements in MRI outcomes with abatacept following the withdrawal of all treatments in patients with early, progressive rheumatoid arthritis

Objectives To assess structural damage progression with subcutaneous abatacept (ABA) in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial following abrupt withdrawal of all rheumatoid arthritis (RA) medication in patients achieving Disease Activity Score (DAS)-defined remission or low disease activity. Methods Patients with early, active RA were randomised to ABA plus methotrexate (ABA/MTX) 125 mg/week, ABA 125 mg/week or MTX for 12 months. All RA treatments were withdrawn after 12 months in patients with DAS28 (C reactive protein (CRP)) <3.2. Adjusted mean changes from baseline in MRI-based synovitis, osteitis and erosion were calculated for the intention-to-treat population. Results 351 patients were randomised and treated: ABA/MTX (n=119), ABA (n=116) or MTX (n=116). Synovitis and osteitis improved, and progression of erosion was statistically less with ABA/MTX versus MTX at month 12 (−2.35 vs −0.68, −2.58 vs −0.68, 0.19 vs 1.53, respectively; p<0.01 for each) and month 18 (−1.34 vs −0.49 −2.03 vs 0.34, 0.13 vs 2.0, respectively; p<0.01 for erosion); ABA benefits were numerically intermediate to those for ABA/MTX and MTX. Conclusions Structural benefits with ABA/MTX or ABA may be maintained 6 months after withdrawal of all treatments in patients who have achieved remission or low disease activity. Trial registration number NCT01142726; Results.

OP0026 Induction of Clinical Remission Followed by Drug-Free Withdrawal with Abatacept Combination and Monotherapy in Early RA: Results from the AVERT Study over 18 Months

Background AVERT (Assessing Very Early Rheumatoid arthirits Treatment) is a Phase IIIb, randomized, active-controlled study to evaluate the efficacy and safety of subcutaneous (SC) abatacept (ABA) in pts with early RA. Objectives To assess ABA + MTX or ABA monotherapy in inducing clinical remission at 12 mths and then maintain it following rapid withdrawal of all RA treatment (biologics, DMARDs, steroids) in pts with early RA. Methods MTX-naïve, anti-CCP2+ pts with early RA (active synovitis in ≥2 joints for ≥8 wks, DAS28 (CRP) >3.2 and onset of symptoms within ≤2 yrs) were included. Pts were randomized to 12 mths of weekly SC ABA 125 mg + MTX, ABA 125 mg monotherapy or MTX alone. Pts with DAS28 (CRP) <3.2 at Mth 12 entered a 12-mth withdrawal period with no treatment. All pts with protocol-defined flare after Mth 15 could receive open-label ABA + MTX. The co-primary endpoints compared ABA + MTX and MTX alone in pts achieving DAS28 (CRP) <2.6 at (1) 12 mths and (2) both 12 and 18 mths. ABA monotherapy was also assessed. Results 351 pts (n=119, 116 and 116 pts in the ABA + MTX, ABA and MTX arms, respectively) with early RA, highly active disease and poor prognosis (at baseline: mean RA duration of 0.56 yrs, mean DAS28 (CRP) of 5.4, mean HAQ of 1.4; 95.2% RF+ and anti-CCP2+) entered the study. At 12 mths, 60.9, 42.5 and 45.2% achieved DAS28 (CRP) <2.6 (ABA + MTX, ABA and MTX, respectively). Odds ratio (OR; 95% CI) for ABA + MTX vs MTX: 2.01 (1.18, 3.43) with p=0.01 and for ABA vs MTX: 0.92 (0.55, 1.57). At most time points, efficacy on signs and symptoms in the ABA monotherapy arm fell between the ABA + MTX and MTX arms (Figure) based on DAS28 (CRP) as well as other measures. Following treatment withdrawal, most pts discontinued due to increase in disease activity (177/223; 79.4%). Rates of pts achieving DAS28 (CRP) <2.6 at both 12 and 18 mths were 14.8, 12.4 and 7.8% for ABA + MTX, ABA and MTX, respectively; OR (95% CI) for ABA + MTX vs MTX: 2.51 (1.02, 6.18), p=0.045 and for ABA vs MTX: 2.04 (0.81, 5.14). In a post hoc analysis, pts who maintained DAS28 (CRP) <2.6 at both Mth 12 and 18 tended to have numerically lower baseline mean symptom duration, DAS28 (CRP), HAQ score and DAS28 (CRP) <2.6 over time during the treatment period compared with pts who achieved only DAS28 (CRP) <2.6 at 12 mths. Over 12 mths of treatment, the number (%) of serious adverse events was 8 (6.7), 14 (12.1) and 9 (7.8) and the number (%) of serious infections was 1 (0.8), 4 (3.4) and 0 in the ABA + MTX, ABA and MTX arms, respectively. Conclusions In this study, in pts with highly active early RA with poor prognosis, abatacept + MTX resulted in significantly higher rates of remission and comparable safety vs MTX alone at 12 mths. At most time points, abatacept monotherapy was more effective than MTX alone. A small but significantly higher number of patients treated with abatacept + MTX were able to maintain drug-free remission compared to MTX. Disclosure of Interest P. Emery Grant/research support: AbbVie, BMS, Merck, Pfizer, Roche, Consultant for: AbbVie, BMS, Merck, Pfizer, Roche, Takeda, G. Burmester Grant/research support: BMS, AbbVie, Pfizer, Medimmune, Novartis, Roche, UCB, Lilly, Consultant for: BMS, AbbVie, Pfizer, MSD, Medimmune, Roche, UCB, Speakers bureau: BMS, AbbVie, Pfizer, MSD, Roche, UCB, V. Bykerk Grant/research support: Amgen, Pfizer, BMS, Janssen, UCB, Roche/Genentech, B. Combe Grant/research support: Pfizer, Roche-Chugai, Speakers bureau: BMS, Merck, Pfizer, Roche-Chugai, UCB, D. Furst Grant/research support: AbbVie, Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Actelion, Amgen, BMS, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Speakers bureau: AbbVie, Actelion, UCB, E. Barre Employee of: BMS, C. Karyekar Employee of: BMS, D. Wong Employee of: BMS, T. Huizinga Grant/research support: EU & Dutch Arthritis Foundation, Consultant for: Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Crescendo Bioscience, Inc, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough, UCB, Inc., Eli Lilly, Speakers bureau: Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough DOI 10.1136/annrheumdis-2014-eular.2132

SAT0001 Antibody Response to Pneumococcal and Influenza Vaccination in Patients With RA Receiving Subcutaneous Abatacept

Background Previous small studies have suggested that responses to some immunizations may be attenuated by intravenous abatacept but remain clinically meaningful.1,2 We investigated the magnitude of response to pneumococcal and influenza vaccination in a larger number of patients (pts) receiving subcutaneous (SC) abatacept therapy. Objectives To evaluate the antibody response to the standard 23-valent pneumococcal polysaccharide vaccine and the 2011–2012 seasonal influenza trivalent vaccine in adult pts with RA on SC abatacept and background DMARDs. Methods These multicentre, open-label sub-studies of the 23-valent pneumococcal polysaccharide vaccine and seasonal influenza vaccine enrolled pts in the ACQUIRE (pneumococcal and influenza) or ATTUNE (pneumococcal) studies. Pts were enrolled at any point during their SC abatacept treatment cycle after completion of ≥3 months’ abatacept treatment. All pts received fixed-dose SC abatacept 125 mg/week with background DMARDs. A pre-vaccination blood sample was collected and vaccines administered, while continuing background SC abatacept and DMARDS. After 28 ± 3 days, a final post-vaccination blood sample was collected. For pneumococcal vaccination, the primary endpoint was the proportion of pts achieving a ≥2-fold increase in post-vaccination titres to ≥3 of 5 evaluated pneumococcal antigens (9V, 14, 18C, 19F and 23F) in the vaccine at Day 28 in pts without a protective antibody level to these antigens at baseline. For influenza vaccination, the primary endpoint was the proportion of pts achieving a ≥4-fold increase in post-vaccination titres to ≥2 of 3 evaluated 2011–2012 influenza antigens (H1N1, H3N2 and Brisbane) at Day 28 in pts without a protective antibody level to these antigens at baseline. Safety and tolerability were assessed throughout the studies. Results Pre- and post-vaccination titres were available for 113/125 and 186/191 enrolled pts receiving the pneumococcal and influenza vaccines, respectively. Among vaccinated pts, 47/113 pneumococcal and 121/186 influenza pts were without protective antibody levels at baseline. Of these pts, 73.9% (34/46) and 61.3% (73/119) met the primary endpoint and demonstrated an immunological response to the pneumococcal vaccine or influenza vaccine, respectively. In all pts who received the vaccine and had pre- and post-vaccination antibody titres available 4 weeks post-vaccination, 83.9% (94/112) in the pneumococcal study demonstrated protective antibody levels (titre ≥1.6 μg/mL to ≥3 of 5 pneumococcal antigens), and 82.1% (151/184) in the influenza study demonstrated protective antibody levels (titre ≥1:40 to ≥2 of 3 influenza antigens). Vaccination during SC abatacept administration was well tolerated, with no new safety signals identified. Conclusions In this group of pts with RA on SC abatacept and background DMARDS, a majority without protective antibody levels at baseline were able to mount an immune response to the pneumococcal and influenza virus vaccines, and vaccination was well tolerated. These data are consistent with previous smaller studies. References Tay L, et al. Arthritis Res Ther 2007;9:R38; Schiff M, et al. Arthritis Rheum 2007;56:S392 Disclosure of Interest R. Alten Grant/research support from: Bristol-Myers Squibb, Merck Pharma GmbH, Wyeth Pharmaceuticals, Pfizer, Consultant for: Abbott Laboratories, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, Speakers bureau: Abbott Laboratories, Bristol-Myers Squibb, Horizon Pharma, Merck Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, C. Bingham 3rd Grant/research support from: Bristol-Myers Squibb, Genentech/Roche, UCB, Janssen/J&J, Consultant for: Abbott, Amgen, Genentech/Roche, Janssen/J&J, Lilly, Novartis, Pfizer, UCB, S. Cohen Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, L. Calabrese Consultant for: Bristol-Myers Squibb, Centocor, Genentech/Roche, Pfizer, sanofi aventis, Savent, Antares, Speakers bureau: Amgen, Bristol-Myers Squibb, Genentech/Roche, J. Curtis Grant/research support from: Roche/Genentech, UCB, Centocor, CORRONA, Amgen, Pfizer, Bristol-Myers Squibb, Crescendo, Abbott, Consultant for: Roche/Genentech, UCB, Centocor, CORRONA, Amgen, Pfizer, Bristol-Myers Squibb, Crescendo, Abbott, A. Block Employee of: Bristol-Myers Squibb, J. Fay Employee of: Bristol-Myers Squibb, S. Kelly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Luo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, D. Wong Employee of: Bristol-Myers Squibb, M. Genovese Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb

AB0469 Can Anti-TNF-Induced Autoantibody Conversion be Reversed by Switching to Abatacept Therapy in Patients with RA on Background MTX?

Background 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.1,2 The effect of subsequent biologic therapy on such pts has not been explored. Objectives 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. Methods 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. Results 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). Conclusions 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. References Charles PJ, et al. Arthritis Rheum 2000;43:2383–90. Eriksson C, et al. Ann Rheum Dis 2005;64:403–7. Disclosure of Interest 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

FRI0152 On Drug and Drug-Free Remission by Baseline Disease Duration in the Avert Trial: Abatacept Versus Methotrexate Comparison in Patients with Early Rheumatoid Arthritis

Background Patients (pts) with RA and longer disease duration generally do not respond as well to treatment with DMARDS as pts with a shorter duration of disease. Earlier use of biologic DMARDs can improve disease control.1,2 In the AVERT (Assessing Very Early Rheumatoid arthritis Treatment) trial, more pts with early RA achieved DAS28 (CRP) <2.6 after 12 mths of treatment with SC abatacept (ABA)+MTX as well as 6 mths after rapid withdrawal of all RA therapy, compared with MTX alone.3 The AVERT trial provides the opportunity to examine outcomes in pts with varying degrees of early disease duration where the definition for disease duration is well defined across groups. Objectives To assess clinical outcomes in pts with early RA and ≤3 mths disease duration compared with pts with >3 to ≤6 or >6 mths disease duration after treatment with SC ABA+MTX or MTX alone, using data from AVERT. Methods Pts with early active RA (clinical synovitis in ≥2 joints for ≥8 wks, persistent symptoms for ≤2 yrs and DAS28 [CRP] ≥3.2), and who were anti-cyclic citrullinated peptide-2 positive, were randomized to SC ABA 125 mg/wk + MTX, SC ABA 125 mg/wk alone or MTX alone for 12 mths. All RA treatment was removed after 12 mths in pts with DAS28 (CRP) <3.2.3 In this post hoc analysis, the proportions of pts achieving protocol-defined remission (DAS28 [CRP] <2.6) or improvement in physical function (HAQ-DI; ≥0.3 units from baseline [BL]) were assessed by disease duration (defined as the duration of persistent symptoms at BL) and treatment group. Adjusted mean changes from BL in HAQ-DI were also evaluated by disease duration. Results Pts were randomized and treated with ABA+MTX (n=119) or MTX (n=116): 36 pts on ABA+MTX and 48 on MTX with ≤3 mths disease duration; 34 pts on ABA+MTX and 29 on MTX with >3 to ≤6 mths disease duration; 49 pts on ABA+MTX and 39 on MTX with >6 mths disease duration. No systematic differences were seen in BL demographics and clinical characteristics when pts were grouped by disease duration. Irrespective of BL disease duration, a higher proportion of ABA+MTX-treated pts achieved DAS-defined remission at Mth 12, and sustained remission at Mth 18, compared with MTX alone. The largest treatment difference in sustained remission following all treatment withdrawal (measured at 12–18 mths) was observed in pts with ≤3 mths disease duration. In the ABA+MTX group, a higher proportion of pts with disease duration ≤3 mths (33%) maintained DAS-defined remission compared with pts with longer disease durations (>3 to ≤6 mths, 14.7%; >6 mths, 10.2%) (Figure). The ABA+MTX group with ≤3 mths disease duration also had the fastest onset of response (Figure). Results for HAQ-DI response were similar to the overall population results, regardless of BL disease duration. Conclusions Disease duration of ≤3 mths was predictive of faster onset of clinical response and the ability to achieve higher rates of drug-free remission following treatment with abatacept +MTX in AVERT. References Westhovens R et al. Ann Rheum Dis 2009;68:1870–7. Emery P et al. Ann Rheum Dis 2010;69:510–6. Emery P et al. Ann Rheum Dis 2014;73(Suppl 2): 69 Disclosure of Interest V. P. Bykerk Grant/research support from: Amgen, Pfizer, Bristol-Myers Squibb, Janssen, UCB, Roche/Genentech, Consultant for: Amgen, Pfizer, Bristol-Myers Squibb, UCB, Roche, G. R. Burmester Grant/research support from: Bristol-Myers Squibb, AbbVie, Pfizer, Medimmune, Novartis, Roche, UCB, Lilly, Consultant for: Bristol-Myers Squibb, AbbVie, Pfizer, MSD, Medimmune, Roche, UCB, Speakers bureau: Bristol-Myers Squibb, AbbVie, Pfizer, MSD, Roche, UCB, B. G. Combe Grant/research support from: Pfizer, Roche-Chugai, Speakers bureau: Bristol-Myers Squibb, Merck, Pfizer, Roche-Chugai, UCB, D. E. Furst Grant/research support from: AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, T. W. J. Huizinga Grant/research support from: EU & Dutch Arthritis Foundation, Consultant for: Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Crescendo Bioscience, Inc, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough, UCB, Inc., Eli Lilly, Meteor Board, D. A. Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, P. Emery Grant/research support from: AbbVie, Merck, Pfizer, Roche, Consultant for: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, Lilly, Novartis

THU0114 Effect of Anti-Cyclic Citrullinated Peptide 2 Immunoglobulin M Serostatus on Efficacy Outcomes Following Treatment with Abatacept Plus Methotrexate in the Avert Trial

Background Anti-citrullinated protein antibodies (ACPA) are a marker of RA, and the presence of the immunoglobulin M (IgM) isotype indicates an ongoing immune response involving the recruitment of naïve B cells.1 Abatacept (ABA) modulates T-cell co-stimulation and has been shown to impact ACPA maturation, including seroconversion of IgM, in the AVERT (Assessing Very Early Rheumatoid arthritis Treatment) trial.2 Objectives To assess the efficacy of treatment with ABA+MTX, ABA monotherapy or MTX alone in patients (pts) from the AVERT trial based on their anti-cyclic citrullinated peptide 2 (CCP2; a surrogate for ACPA) IgM serostatus at baseline (BL), and seroconversion (anti-CCP2 IgM positive to negative) through 1 year. Methods The AVERT trial has been described previously.3 In this post hoc analysis, pt samples were analysed by ELISA to determine anti-CCP2 IgM serostatus. Efficacy outcomes analysed by BL anti-CCP2 IgM serostatus included remission rate at 12 mths (CDAI, SDAI, Boolean and DAS28 [CRP] <2.6-defined remission), and adjusted mean change in DAS28 (CRP) and HAQ-DI over time (samples taken every 28 days up to Mth 12 and analysed with a longitudinal repeated-measures model). Boolean remission was analysed in pts who seroconverted. Results In the ABA+MTX treatment arm, a higher proportion of pts who were anti-CCP2 IgM positive at BL achieved remission by all indices compared with pts who were BL IgM negative (Figure). This trend was most clearly observed in the stringent indices of CDAI, SDAI and Boolean remission, compared with DAS28 (CRP)-defined remission. This trend was not observed in either the ABA monotherapy or MTX alone arms. Mean improvement in DAS28 (CRP) and HAQ-DI over time was also greatest in BL anti-CCP2 IgM-positive pts treated with ABA+MTX. A numerically higher proportion of pts who seroconverted from anti-CCP2 IgM positive at BL to negative at Mth 12 achieved Boolean remission versus pts who remained seropositive in the ABA+MTX and ABA monotherapy arms (Table). Conclusions Abatacept in combination with MTX had greater clinical efficacy in pts who were anti-CCP2 IgM positive at BL than in those who were anti-CCP2 IgM negative at BL, and in those who seroconverted over time than those who did not, suggesting that the impact on ACPA is associated with clinical benefit. References Verpoort KN, et al. Arthritis Rheum 2006;54:3799–808. Huizinga TWJ, et al. Arthritis Rheum 2014;66:S666. Poster 1515. Emery P, et al. Ann Rheum Dis 2015:74:19–26. Disclosure of Interest T. W. J. Huizinga Grant/research support from: EU & Dutch Arthritis Foundation, Consultant for: Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Crescendo Bioscience, Inc, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough, UCB, Inc., Eli Lilly, Meteor Board, Speakers bureau: Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough, S. E. Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Johnsen Employee of: Bristol-Myers Squibb, J. Zhu Employee of: Bristol-Myers Squibb, D. E. Furst Grant/research support from: AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Speakers bureau: (CME only) AbbVie, Actelion, UCB, V. P. Bykerk Grant/research support from: Amgen, Pfizer, Bristol-Myers Squibb, Janssen, UCB, Roche/Genentech, Consultant for: Amgen, Pfizer, Bristol-Myers Squibb, UCB, Roche, G. R. Burmester Grant/research support from: Bristol-Myers Squibb, AbbVie, Pfizer, Medimmune, Novartis, Roche, UCB, Lilly, Consultant for: Bristol-Myers Squibb, AbbVie, Pfizer, MSD, Medimmune, Roche, UCB, Speakers bureau: Bristol-Myers Squibb, AbbVie, Pfizer, MSD, Roche, UCB, B. G. Combe Grant/research support from: Pfizer, Roche-Chugai, Speakers bureau: Bristol-Myers Squibb, Merck, Pfizer, Roche-Chugai, UCB, D. A. Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, L. A. Trouw: None declared, R. E. M. Toes: None declared, P. Emery Grant/research support from: Abbvie, Merck, Pfizer, Roche, Consultant for: Abbvie, Bristol-Myers Squibb, Merck, Pfizer, Roche, Lilly, Novartis