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  • sat0104 maintenance of sdai remission and patient reported outcomes pros following dose de escalation of abatacept in mtx naive anti citrullinated Protein Antibody acpa patients with early ra results from avert 2 a randomised phase iiib study
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: Paul Emery, T W J Huizinga, Yoshiya Tanaka, V P Bykerk, Gustavo Citera, Clifton O Bingham, S Banerjee, Sean E Connolly, J Zhuo, R Wong
    Abstract:

    Background: The Phase IIIb Assessing Very Early RA Treatment (AVERT)-2 trial (NCT02504268) evaluated SC abatacept (ABA) + MTX vs ABA placebo (PBO) + MTX in ACPA+ patients (pts) with early, active RA.1 Results from the 56-wk induction period (IP) showed a significantly greater proportion of pts treated with ABA + MTX (vs MTX alone) reported clinically meaningful improvements in HAQ-DI, global disease activity and pain, which were sustained at 52 wks.2 Objectives: To report maintenance of SDAI remission and PROs from the AVERT-2 de-escalation (D-E) period. Methods: Pts received blinded SC ABA (125 mg once wkly [QW]) + MTX or ABA PBO + MTX induction treatment for 56 wks. In this analysis, pts who completed induction with ABA + MTX and had sustained SDAI remission (≤3.3 at Wks 40 and 52) were re-randomised 1:1:1 to ABA QW + MTX, stepwise D-E (ABA every other wk + MTX for 24 wks then ABA PBO + MTX for 24 wks), or ABA QW + MTX PBO for 48 wks in the D-E period. PROs included physical function (HAQ-DI [0–3; decrease=improvement] and Short-Form 36 [SF-36] v2.0 Physical Functioning Scale [PFS]; 0–100; increase=improvement), and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] score; 0–52; decrease=improvement). Endpoints included: proportion of pts in SDAI remission and pts with HAQ-DI response (decrease from IP Day [D]1 in HAQ-DI ≥0.30); adjusted mean change (adMC) from D-E D1 in HAQ-DI, SF-36 PFS or FACIT-F to D-E Wk 48. adMCs were estimated using a mixed effect model with repeated measures. Results: 147 ABA + MTX-treated pts were re-randomised in the D-E period. Across re-randomised arms, the range of mean scores was 1.87–2.52 for SDAI and 0.18–0.30 for HAQ-DI at entry into D-E period (D-E D1). 74% of pts receiving ABA QW + MTX maintained SDAI remission at D-E Wk 48 (Fig 1); this proportion was higher than in the ABA withdrawal and ABA QW + MTX PBO arms. Pts continuing ABA QW + MTX maintained HAQ-DI response during D-E (Fig 1), but by D-E Wk 48 the proportion of pts with HAQ-DI response in the ABA withdrawal arm declined by 30%. At D-E Wk 48, a small numerical decrease (adMC –0.04) in HAQ-DI was observed in the ABA QW + MTX arm; increases were seen in the withdrawal (adMC 0.26) and ABA QW + MTX PBO arms (adMC 0.16). By D-E Wk 48, SF-36 PFS increased (adMC 1.68) in the ABA QW + MTX arm but decreased in the withdrawal (adMC –3.34) and ABA QW + MTX PBO (adMC –1.45) arms. FACIT-F score increased during D-E in all arms, but the increase at D-E Wk 48 was lower in the ABA QW + MTX arm (adMC 0.79) vs the withdrawal (adMC 4.12) and ABA QW + MTX PBO (adMC 2.41) arms. Similar trends were seen for other PROs including Work Productivity and Activity Impairment-RA; while activity impairment remained stable in the ABA QW + MTX arm, there was a trend for worsening in the withdrawal arm. Conclusion: In the AVERT-2 D-E period, continued combination therapy (abatacept + MTX) resulted in maintenance of benefits on PROs, particularly physical functioning, in seropositive pts with early RA. D-E of abatacept followed by complete withdrawal was associated with the greatest loss of remission as well as worsening of PROs. The PRO results corresponded well to the maintenance of clinical (SDAI) remission. References: [1]Emery P, et al. ACR 2018; San Diego, USA: Poster 563. [2]Emery P, et al. ACR 2019; Atlanta, USA: Poster 1423. Acknowledgments: Joanna Wright (medical writing, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Vivian Bykerk: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Subhashis Banerjee Shareholder of: AbbVie, Bristol-Myers Squibb, Lily, Pfizer, Employee of: Bristol-Myers Squibb (current); AbbVie, Lily, Pfizer (past), Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Karissa Lozenski Employee of: Bristol-Myers Squibb, Yedid Elbez Consultant of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB

  • thu0095 impact of baseline erosion score on response to treatment and future radiological damage in avert 2 a randomised phase iiib study of abatacept in mtx naive anti citrullinated Protein Antibody positive acpa patients with early ra
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: C Pachai, T W J Huizinga, Yoshiya Tanaka, V P Bykerk, Gustavo Citera, Clifton O Bingham, Sean E Connolly, R Wong, J Landis, K H G Huang
    Abstract:

    Background: Bone erosions are associated with poor prognosis in patients (pts) with RA. They can be associated with subclinical inflammation and independently predict future radiological damage.1 The Phase IIIb Assessing Very Early RA Treatment (AVERT)-2 (NCT02504268) trial evaluated abatacept (ABA)+MTX in MTX-naive, ACPA+ pts with early RA.2 Objectives: To explore the impact of baseline (BL) X-ray erosion scores (ES) on clinical response and future radiological damage over 1 yr in different groups of pts from AVERT-2. Methods: BL and Wk 52 X-ray data were evaluated using Sharp/van der Heijde score. SDAI remission rates (RRs; ≤3.3), unadjusted mean changes from BL (CfB) and duration of/time to sustained remission over 52 wks were evaluated. Radiographic progression was assessed at Wk 52 using CfB in ES. A range of BL ES cut-offs were evaluated to highlight key findings through comparison of pts with low and high ES. Results: Of 994 pts in the study, 964 (97%) had BL (median 2.0, interquartile range [IQR] 0.5–5.1) and 792 (80%) had BL and Wk 52 (median 2.5, IQR 1.0–6.5) ES. Results in Table 1 are based on ES cut-offs of 2 and 5, resulting in 53% and 75%, respectively, of pts in low ES groups. In pts who received ABA+MTX, those with low ES had higher SDAI RRs over 52 wks vs pts with high ES. The relationship was more pronounced for higher cut-offs. This was not observed with ABA placebo+MTX (MTX). Greater reduction of mean CfB in SDAI was achieved in pts with high vs low ES who received ABA+MTX. This was not observed with MTX. Pts who received ABA+MTX had longer duration and shorter time to sustained SDAI remission vs MTX. With ABA+MTX, pts with low ES had longer duration and shorter time to sustained SDAI remission vs high ES. This was not observed with MTX. Mean CfB in ES at Wk 52 was lower in the ABA+MTX arm vs the MTX arm. ABA seemed to equally protect pts with low and high ES; with MTX, pts with high ES had higher mean CfB in ES at Wk 52 than pts with low ES. Conclusion: This erosion-based stratification of the AVERT-2 early seropositive RA population emphasizes the importance of treating pts prior to the accumulation of erosive disease. Abatacept+MTX led to higher SDAI RRs in pts with low vs high ES and provided further protection vs MTX alone against future radiological damage in pts with high ES. Additional statistical modelling and adjustment for confounding factors at BL is warranted. References: [1]van Nies JAB, et al. Ann Rheum Dis 2015;74:883–9. [2]Emery P, et al. ACR/ARHP 2018; Chicago, USA:abstract 563. Acknowledgments: Fiona Boswell (editorial assistance, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: Chahin Pachai Employee of: Bristol-Myers Squibb, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Jessica Landis Employee of: Bristol-Myers Squibb, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Vivian Bykerk: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Shuyan Du Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Wendy Hayes Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Chun Wu Employee of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor)

  • fri0090 maintenance of clinical response with abatacept in combination with mtx in individual patients with early ra who are mtx naive and anti citrullinated Protein Antibody acpa results from the induction period of avert 2 a randomised phase iiib study
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: Paul Emery, T W J Huizinga, Yoshiya Tanaka, V P Bykerk, Gustavo Citera, Clifton O Bingham, Sean E Connolly, K H G Huang, Y Elbez, R Wong
    Abstract:

    Background: In the 56-wk induction period (IP) of the Phase IIIb Assessing Very Early RA Treatment (AVERT)-2 trial (NCT02504268), more patients (pts) achieved SDAI remission (≤3.3) with abatacept (ABA) + MTX vs ABA placebo (PBO) + MTX at IP Wk 52.1 It is unknown whether each individual pt within a treatment (Tx) group achieves and sustains the same efficacy endpoints at all time points during the IP. Objectives: To investigate whether ABA effectiveness is sustained by individual pts who achieved SDAI remission (≤3.3), SDAI low disease activity (LDA; >3.3–11), DAS28 (CRP) Methods: Pts were randomised 3:2 to blinded SC ABA (125 mg/wk) + MTX or ABA PBO + MTX induction Tx for 56 wks. Key inclusion criteria: age ≥18 yrs; RA diagnosis (ACR/EULAR 2010 criteria); RA duration ≤6 mos; SDAI >11; ACPA+; CRP >3 mg/L or ESR ≥28 mm/h; TJC ≥3 and SJC ≥3; DMARD naive. Response rates were investigated by Tx arm in the cohort 1 analysis population (all randomised pts treated in the IP [intent-to-treat analysis]). Results: Of randomised cohort 1, 752 pts were treated during the IP: 451 with ABA + MTX and 301 with ABA PBO + MTX. Baseline characteristics were similar across Tx arms.1 Stringent SDAI remission endpoint at IP Wk 24 was achieved by 22% of ABA + MTX-treated pts; of these, 56% sustained SDAI remission at IP Wks 40/52 (Table). A similar proportion of ABA + MTX-treated pts achieved (17%) and sustained (58%) Boolean remission at IP Wks 24 and 40/52. At IP Wk 24, 42% of ABA + MTX-treated pts achieved DAS28 (CRP) Conclusion: The majority of individual pts with RA who achieved clinically stringent endpoints such as SDAI remission, DAS28 (CRP) References: [1]Emery P, et al. ACR 2018; San Diego, USA: Poster 563. Acknowledgments: Lola Parfitt (medical writing, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Vivian Bykerk: None declared, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Yedid Elbez Consultant of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Karissa Lozenski Employee of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB

T W J Huizinga - One of the best experts on this subject based on the ideXlab platform.

  • thu0095 impact of baseline erosion score on response to treatment and future radiological damage in avert 2 a randomised phase iiib study of abatacept in mtx naive anti citrullinated Protein Antibody positive acpa patients with early ra
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: C Pachai, T W J Huizinga, Yoshiya Tanaka, V P Bykerk, Gustavo Citera, Clifton O Bingham, Sean E Connolly, R Wong, J Landis, K H G Huang
    Abstract:

    Background: Bone erosions are associated with poor prognosis in patients (pts) with RA. They can be associated with subclinical inflammation and independently predict future radiological damage.1 The Phase IIIb Assessing Very Early RA Treatment (AVERT)-2 (NCT02504268) trial evaluated abatacept (ABA)+MTX in MTX-naive, ACPA+ pts with early RA.2 Objectives: To explore the impact of baseline (BL) X-ray erosion scores (ES) on clinical response and future radiological damage over 1 yr in different groups of pts from AVERT-2. Methods: BL and Wk 52 X-ray data were evaluated using Sharp/van der Heijde score. SDAI remission rates (RRs; ≤3.3), unadjusted mean changes from BL (CfB) and duration of/time to sustained remission over 52 wks were evaluated. Radiographic progression was assessed at Wk 52 using CfB in ES. A range of BL ES cut-offs were evaluated to highlight key findings through comparison of pts with low and high ES. Results: Of 994 pts in the study, 964 (97%) had BL (median 2.0, interquartile range [IQR] 0.5–5.1) and 792 (80%) had BL and Wk 52 (median 2.5, IQR 1.0–6.5) ES. Results in Table 1 are based on ES cut-offs of 2 and 5, resulting in 53% and 75%, respectively, of pts in low ES groups. In pts who received ABA+MTX, those with low ES had higher SDAI RRs over 52 wks vs pts with high ES. The relationship was more pronounced for higher cut-offs. This was not observed with ABA placebo+MTX (MTX). Greater reduction of mean CfB in SDAI was achieved in pts with high vs low ES who received ABA+MTX. This was not observed with MTX. Pts who received ABA+MTX had longer duration and shorter time to sustained SDAI remission vs MTX. With ABA+MTX, pts with low ES had longer duration and shorter time to sustained SDAI remission vs high ES. This was not observed with MTX. Mean CfB in ES at Wk 52 was lower in the ABA+MTX arm vs the MTX arm. ABA seemed to equally protect pts with low and high ES; with MTX, pts with high ES had higher mean CfB in ES at Wk 52 than pts with low ES. Conclusion: This erosion-based stratification of the AVERT-2 early seropositive RA population emphasizes the importance of treating pts prior to the accumulation of erosive disease. Abatacept+MTX led to higher SDAI RRs in pts with low vs high ES and provided further protection vs MTX alone against future radiological damage in pts with high ES. Additional statistical modelling and adjustment for confounding factors at BL is warranted. References: [1]van Nies JAB, et al. Ann Rheum Dis 2015;74:883–9. [2]Emery P, et al. ACR/ARHP 2018; Chicago, USA:abstract 563. Acknowledgments: Fiona Boswell (editorial assistance, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: Chahin Pachai Employee of: Bristol-Myers Squibb, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Jessica Landis Employee of: Bristol-Myers Squibb, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Vivian Bykerk: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Shuyan Du Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Wendy Hayes Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Chun Wu Employee of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor)

  • sat0104 maintenance of sdai remission and patient reported outcomes pros following dose de escalation of abatacept in mtx naive anti citrullinated Protein Antibody acpa patients with early ra results from avert 2 a randomised phase iiib study
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: Paul Emery, T W J Huizinga, Yoshiya Tanaka, V P Bykerk, Gustavo Citera, Clifton O Bingham, S Banerjee, Sean E Connolly, J Zhuo, R Wong
    Abstract:

    Background: The Phase IIIb Assessing Very Early RA Treatment (AVERT)-2 trial (NCT02504268) evaluated SC abatacept (ABA) + MTX vs ABA placebo (PBO) + MTX in ACPA+ patients (pts) with early, active RA.1 Results from the 56-wk induction period (IP) showed a significantly greater proportion of pts treated with ABA + MTX (vs MTX alone) reported clinically meaningful improvements in HAQ-DI, global disease activity and pain, which were sustained at 52 wks.2 Objectives: To report maintenance of SDAI remission and PROs from the AVERT-2 de-escalation (D-E) period. Methods: Pts received blinded SC ABA (125 mg once wkly [QW]) + MTX or ABA PBO + MTX induction treatment for 56 wks. In this analysis, pts who completed induction with ABA + MTX and had sustained SDAI remission (≤3.3 at Wks 40 and 52) were re-randomised 1:1:1 to ABA QW + MTX, stepwise D-E (ABA every other wk + MTX for 24 wks then ABA PBO + MTX for 24 wks), or ABA QW + MTX PBO for 48 wks in the D-E period. PROs included physical function (HAQ-DI [0–3; decrease=improvement] and Short-Form 36 [SF-36] v2.0 Physical Functioning Scale [PFS]; 0–100; increase=improvement), and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] score; 0–52; decrease=improvement). Endpoints included: proportion of pts in SDAI remission and pts with HAQ-DI response (decrease from IP Day [D]1 in HAQ-DI ≥0.30); adjusted mean change (adMC) from D-E D1 in HAQ-DI, SF-36 PFS or FACIT-F to D-E Wk 48. adMCs were estimated using a mixed effect model with repeated measures. Results: 147 ABA + MTX-treated pts were re-randomised in the D-E period. Across re-randomised arms, the range of mean scores was 1.87–2.52 for SDAI and 0.18–0.30 for HAQ-DI at entry into D-E period (D-E D1). 74% of pts receiving ABA QW + MTX maintained SDAI remission at D-E Wk 48 (Fig 1); this proportion was higher than in the ABA withdrawal and ABA QW + MTX PBO arms. Pts continuing ABA QW + MTX maintained HAQ-DI response during D-E (Fig 1), but by D-E Wk 48 the proportion of pts with HAQ-DI response in the ABA withdrawal arm declined by 30%. At D-E Wk 48, a small numerical decrease (adMC –0.04) in HAQ-DI was observed in the ABA QW + MTX arm; increases were seen in the withdrawal (adMC 0.26) and ABA QW + MTX PBO arms (adMC 0.16). By D-E Wk 48, SF-36 PFS increased (adMC 1.68) in the ABA QW + MTX arm but decreased in the withdrawal (adMC –3.34) and ABA QW + MTX PBO (adMC –1.45) arms. FACIT-F score increased during D-E in all arms, but the increase at D-E Wk 48 was lower in the ABA QW + MTX arm (adMC 0.79) vs the withdrawal (adMC 4.12) and ABA QW + MTX PBO (adMC 2.41) arms. Similar trends were seen for other PROs including Work Productivity and Activity Impairment-RA; while activity impairment remained stable in the ABA QW + MTX arm, there was a trend for worsening in the withdrawal arm. Conclusion: In the AVERT-2 D-E period, continued combination therapy (abatacept + MTX) resulted in maintenance of benefits on PROs, particularly physical functioning, in seropositive pts with early RA. D-E of abatacept followed by complete withdrawal was associated with the greatest loss of remission as well as worsening of PROs. The PRO results corresponded well to the maintenance of clinical (SDAI) remission. References: [1]Emery P, et al. ACR 2018; San Diego, USA: Poster 563. [2]Emery P, et al. ACR 2019; Atlanta, USA: Poster 1423. Acknowledgments: Joanna Wright (medical writing, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Vivian Bykerk: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Subhashis Banerjee Shareholder of: AbbVie, Bristol-Myers Squibb, Lily, Pfizer, Employee of: Bristol-Myers Squibb (current); AbbVie, Lily, Pfizer (past), Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Karissa Lozenski Employee of: Bristol-Myers Squibb, Yedid Elbez Consultant of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB

  • fri0090 maintenance of clinical response with abatacept in combination with mtx in individual patients with early ra who are mtx naive and anti citrullinated Protein Antibody acpa results from the induction period of avert 2 a randomised phase iiib study
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: Paul Emery, T W J Huizinga, Yoshiya Tanaka, V P Bykerk, Gustavo Citera, Clifton O Bingham, Sean E Connolly, K H G Huang, Y Elbez, R Wong
    Abstract:

    Background: In the 56-wk induction period (IP) of the Phase IIIb Assessing Very Early RA Treatment (AVERT)-2 trial (NCT02504268), more patients (pts) achieved SDAI remission (≤3.3) with abatacept (ABA) + MTX vs ABA placebo (PBO) + MTX at IP Wk 52.1 It is unknown whether each individual pt within a treatment (Tx) group achieves and sustains the same efficacy endpoints at all time points during the IP. Objectives: To investigate whether ABA effectiveness is sustained by individual pts who achieved SDAI remission (≤3.3), SDAI low disease activity (LDA; >3.3–11), DAS28 (CRP) Methods: Pts were randomised 3:2 to blinded SC ABA (125 mg/wk) + MTX or ABA PBO + MTX induction Tx for 56 wks. Key inclusion criteria: age ≥18 yrs; RA diagnosis (ACR/EULAR 2010 criteria); RA duration ≤6 mos; SDAI >11; ACPA+; CRP >3 mg/L or ESR ≥28 mm/h; TJC ≥3 and SJC ≥3; DMARD naive. Response rates were investigated by Tx arm in the cohort 1 analysis population (all randomised pts treated in the IP [intent-to-treat analysis]). Results: Of randomised cohort 1, 752 pts were treated during the IP: 451 with ABA + MTX and 301 with ABA PBO + MTX. Baseline characteristics were similar across Tx arms.1 Stringent SDAI remission endpoint at IP Wk 24 was achieved by 22% of ABA + MTX-treated pts; of these, 56% sustained SDAI remission at IP Wks 40/52 (Table). A similar proportion of ABA + MTX-treated pts achieved (17%) and sustained (58%) Boolean remission at IP Wks 24 and 40/52. At IP Wk 24, 42% of ABA + MTX-treated pts achieved DAS28 (CRP) Conclusion: The majority of individual pts with RA who achieved clinically stringent endpoints such as SDAI remission, DAS28 (CRP) References: [1]Emery P, et al. ACR 2018; San Diego, USA: Poster 563. Acknowledgments: Lola Parfitt (medical writing, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Vivian Bykerk: None declared, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Yedid Elbez Consultant of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Karissa Lozenski Employee of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB

  • fine specificity of the anti citrullinated Protein Antibody response is influenced by the shared epitope alleles
    Arthritis & Rheumatism, 2007
    Co-Authors: Kirsten N Verpoort, A Ioanfacsinay, Jan W Drijfhout, K Cheung, A H M Van Der Helmvan Mil, J K De Vriesbouwstra, C F Allaart, R R P De Vries, Ferdinand C Breedveld, T W J Huizinga
    Abstract:

    Objective In classic studies on the genetic background of Antibody production, the major histocompatibility complex (MHC) has been shown to act as the most prominent immune response gene that controls the magnitude and the specificity of Antibody production. The strongest genetic risk factor for rheumatoid arthritis (RA), the human MHC HLA–DRB1 shared epitope (SE) alleles, predisposes for antibodies against citrullinated Proteins (ACPAs). ACPA levels are higher in SE-positive patients with RA than in SE-negative patients with RA. The aim of the present study was to determine whether SE influences not only the magnitude but also the specificity of the ACPA response. Methods In 2 cohorts of anti–citrullinated peptide 2–positive patients with RA, one from a study of recent-onset arthritis (n = 206) and the other from a treatment strategy study (n = 141), serum antibodies against a citrullinated peptide derived from vimentin (cVim) and antibodies against a citrullinated fibrinogen peptide (cFibr) were determined by enzyme-linked immunosorbent assay. HLA–DRB1 genotyping was performed. Results In the first cohort, SE alleles were significantly associated with the presence of antibodies against cVim (odds ratio [OR] 4.95, 95% confidence interval [95% CI] 1.87–15.3) and were not significantly associated with the presence of antibodies against cFibr (OR 1.71, 95% CI 0.70–4.14). These results were replicated in the second cohort (OR 5.05, 95% CI 1.92–13.6 and OR 1.19, 95% CI 0.30–3.97, respectively). Conclusion In 2 cohorts of ACPA-positive patients with RA, SE alleles predisposed for the development of antibodies against cVim but not for the development of antibodies against cFibr. These data indicate that SE alleles act as “classic” immune response genes in the ACPA response, because they influence both the magnitude and the specificity of this RA-specific Antibody response.

Jeremy Sokolove - One of the best experts on this subject based on the ideXlab platform.

  • Alveolar Bone Loss Is Associated With Circulating Anti-Citrullinated Protein Antibody (ACPA) in Patients With
    2015
    Co-Authors: Rheumatoid Arthritis, Jeremy Sokolove
    Abstract:

    citrullinated Protein Antibody (ACPA)-positive rheumatoid arthritis (RA) patients versus control patients with osteoarthritis (OA); and 2) the association of ABL with RA disease activity and ACPA concentra-tions, including multiple antigen–specific ACPA. Methods: This multicenter case-control study includes 617 patients diagnosed with RA (n = 287) or OA (n = 330). Panoramic radiographs were taken; patients were categorized into low, moderate, or high tertiles based on mean percentage ABL. Serum ACPA was measured using second-generation anti-cyclic citrullinated peptide enzyme-linked immunosorbent assay and a multiplex platform to assess dis-tinct antigen-specific ACPA. A generalized linear mixed model for binary data was used to compare stratified ABL in RA versus OA patients. Associations of moderate and high ABL (versus low) with RA disease activity and severity measures were examined using multivariate regression. Antigen-specific ACPA responses were compared among ABL tertiles using significance analysis of microarrays. Results: ACPA-positive patients with RA had a significantly higher mean percentage of sites with ABL>20 % compared with patients with OA (P = 0.03). After multivariate adjustment, greater ABL was signif-icantly associated with higher serum ACPA concentration (P = 0.004), 28-joint Disease Activity Score (P = 0.023), health assessment questionnaire disability (P = 0.05), tender joint count (P = 0.02) and joint space narrowing scores (P = 0.05) among patients with RA. ACPAs targeting citrullinated vimentin and histone were significantly higher in moderate and high ABL groups versus low, regardless of smoking status (q <0.1%). Conclusions: Greater ABL was associated with higher ACPA, consistent with findings at articular sites. ACPA targeting could provide novel insight into important linkages between RA and periodontitis. J Periodon-tol 2015;86:222-231

  • alveolar bone loss is associated with circulating anti citrullinated Protein Antibody acpa in patients with rheumatoid arthritis
    Journal of Periodontology, 2015
    Co-Authors: Shawneen M Gonzalez, Jeffrey B Payne, Geoffrey M Thiele, Alan R Erickson, Paul G Johnson, Marian J Schmid, Grant W Cannon, Gail S Kerr, Andreas M Reimold, Jeremy Sokolove
    Abstract:

    Background: This study examines: 1) alveolar bone loss (ABL), a hallmark of periodontitis, in Anti-Citrullinated Protein Antibody (ACPA)-positive rheumatoid arthritis (RA) patients versus control patients with osteoarthritis (OA); and 2) the association of ABL with RA disease activity and ACPA concentrations, including multiple antigen–specific ACPA.Methods: This multicenter case-control study includes 617 patients diagnosed with RA (n = 287) or OA (n = 330). Panoramic radiographs were taken; patients were categorized into low, moderate, or high tertiles based on mean percentage ABL. Serum ACPA was measured using second-generation anticyclic citrullinated peptide enzyme-linked immunosorbent assay and a multiplex platform to assess distinct antigen-specific ACPA. A generalized linear mixed model for binary data was used to compare stratified ABL in RA versus OA patients. Associations of moderate and high ABL (versus low) with RA disease activity and severity measures were examined using multivariate regres...

  • rheumatoid factor as a potentiator of anti citrullinated Protein Antibody mediated inflammation in rheumatoid arthritis
    Arthritis & Rheumatism, 2014
    Co-Authors: Jeremy Sokolove, Geoffrey M Thiele, Andreas M Reimold, Dannette S Johnson, Lauren J Lahey, Catriona A Wagner, Danye Cheng, Kaleb Michaud, Harlan Sayles, Liron Caplan
    Abstract:

    Objective The co-occurrence of rheumatoid factor (RF) and anti–citrullinated Protein Antibody (ACPA) positivity in rheumatoid arthritis (RA) is well described. However, the mechanisms underlying the potential interaction between these 2 distinct autoantibodies have not been well defined. The aim of this study was to evaluate the epidemiologic and molecular interaction of ACPAs and RF and its association with both disease activity and measures of RA-associated inflammation. Methods In a cohort of 1,488 US veterans with RA, measures of disease activity and serum levels of cytokines and multiplex ACPAs were compared between the following groups of patients: double-negative (anti–cyclic citrullinated peptide [anti-CCP]−/RF−), anti-CCP+/RF−, anti-CCP−/RF+, or double-positive (anti-CCP+/RF+). Additional studies were performed using an in vitro immune complex (IC) stimulation assay in which macrophages were incubated with ACPA ICs in the presence or absence of monoclonal IgM-RF, and tumor necrosis factor α production measured as a readout of macrophage activation. Results Compared with the double-negative subgroup (as well as each single-positive subgroup), the double-positive subgroup exhibited higher disease activity as well as higher levels of C-reactive Protein and inflammatory cytokines (all P < 0.001). In vitro stimulation of macrophages by ACPA ICs increased cytokine production, and the addition of monoclonal IgM-RF significantly increased macrophage tumor necrosis factor α production (P = 0.003 versus ACPA ICs alone). Conclusion The combined presence of ACPAs and IgM-RF mediates increased proinflammatory cytokine production in vitro and is associated with increased systemic inflammation and disease activity in RA. Our data suggest that IgM-RF enhances the capacity of ACPA ICs to stimulate macrophage cytokine production, thereby providing a mechanistic link by which RF enhances the pathogenicity of ACPA ICs in RA.

V P Bykerk - One of the best experts on this subject based on the ideXlab platform.

  • sat0104 maintenance of sdai remission and patient reported outcomes pros following dose de escalation of abatacept in mtx naive anti citrullinated Protein Antibody acpa patients with early ra results from avert 2 a randomised phase iiib study
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: Paul Emery, T W J Huizinga, Yoshiya Tanaka, V P Bykerk, Gustavo Citera, Clifton O Bingham, S Banerjee, Sean E Connolly, J Zhuo, R Wong
    Abstract:

    Background: The Phase IIIb Assessing Very Early RA Treatment (AVERT)-2 trial (NCT02504268) evaluated SC abatacept (ABA) + MTX vs ABA placebo (PBO) + MTX in ACPA+ patients (pts) with early, active RA.1 Results from the 56-wk induction period (IP) showed a significantly greater proportion of pts treated with ABA + MTX (vs MTX alone) reported clinically meaningful improvements in HAQ-DI, global disease activity and pain, which were sustained at 52 wks.2 Objectives: To report maintenance of SDAI remission and PROs from the AVERT-2 de-escalation (D-E) period. Methods: Pts received blinded SC ABA (125 mg once wkly [QW]) + MTX or ABA PBO + MTX induction treatment for 56 wks. In this analysis, pts who completed induction with ABA + MTX and had sustained SDAI remission (≤3.3 at Wks 40 and 52) were re-randomised 1:1:1 to ABA QW + MTX, stepwise D-E (ABA every other wk + MTX for 24 wks then ABA PBO + MTX for 24 wks), or ABA QW + MTX PBO for 48 wks in the D-E period. PROs included physical function (HAQ-DI [0–3; decrease=improvement] and Short-Form 36 [SF-36] v2.0 Physical Functioning Scale [PFS]; 0–100; increase=improvement), and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] score; 0–52; decrease=improvement). Endpoints included: proportion of pts in SDAI remission and pts with HAQ-DI response (decrease from IP Day [D]1 in HAQ-DI ≥0.30); adjusted mean change (adMC) from D-E D1 in HAQ-DI, SF-36 PFS or FACIT-F to D-E Wk 48. adMCs were estimated using a mixed effect model with repeated measures. Results: 147 ABA + MTX-treated pts were re-randomised in the D-E period. Across re-randomised arms, the range of mean scores was 1.87–2.52 for SDAI and 0.18–0.30 for HAQ-DI at entry into D-E period (D-E D1). 74% of pts receiving ABA QW + MTX maintained SDAI remission at D-E Wk 48 (Fig 1); this proportion was higher than in the ABA withdrawal and ABA QW + MTX PBO arms. Pts continuing ABA QW + MTX maintained HAQ-DI response during D-E (Fig 1), but by D-E Wk 48 the proportion of pts with HAQ-DI response in the ABA withdrawal arm declined by 30%. At D-E Wk 48, a small numerical decrease (adMC –0.04) in HAQ-DI was observed in the ABA QW + MTX arm; increases were seen in the withdrawal (adMC 0.26) and ABA QW + MTX PBO arms (adMC 0.16). By D-E Wk 48, SF-36 PFS increased (adMC 1.68) in the ABA QW + MTX arm but decreased in the withdrawal (adMC –3.34) and ABA QW + MTX PBO (adMC –1.45) arms. FACIT-F score increased during D-E in all arms, but the increase at D-E Wk 48 was lower in the ABA QW + MTX arm (adMC 0.79) vs the withdrawal (adMC 4.12) and ABA QW + MTX PBO (adMC 2.41) arms. Similar trends were seen for other PROs including Work Productivity and Activity Impairment-RA; while activity impairment remained stable in the ABA QW + MTX arm, there was a trend for worsening in the withdrawal arm. Conclusion: In the AVERT-2 D-E period, continued combination therapy (abatacept + MTX) resulted in maintenance of benefits on PROs, particularly physical functioning, in seropositive pts with early RA. D-E of abatacept followed by complete withdrawal was associated with the greatest loss of remission as well as worsening of PROs. The PRO results corresponded well to the maintenance of clinical (SDAI) remission. References: [1]Emery P, et al. ACR 2018; San Diego, USA: Poster 563. [2]Emery P, et al. ACR 2019; Atlanta, USA: Poster 1423. Acknowledgments: Joanna Wright (medical writing, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Vivian Bykerk: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Subhashis Banerjee Shareholder of: AbbVie, Bristol-Myers Squibb, Lily, Pfizer, Employee of: Bristol-Myers Squibb (current); AbbVie, Lily, Pfizer (past), Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Karissa Lozenski Employee of: Bristol-Myers Squibb, Yedid Elbez Consultant of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB

  • thu0095 impact of baseline erosion score on response to treatment and future radiological damage in avert 2 a randomised phase iiib study of abatacept in mtx naive anti citrullinated Protein Antibody positive acpa patients with early ra
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: C Pachai, T W J Huizinga, Yoshiya Tanaka, V P Bykerk, Gustavo Citera, Clifton O Bingham, Sean E Connolly, R Wong, J Landis, K H G Huang
    Abstract:

    Background: Bone erosions are associated with poor prognosis in patients (pts) with RA. They can be associated with subclinical inflammation and independently predict future radiological damage.1 The Phase IIIb Assessing Very Early RA Treatment (AVERT)-2 (NCT02504268) trial evaluated abatacept (ABA)+MTX in MTX-naive, ACPA+ pts with early RA.2 Objectives: To explore the impact of baseline (BL) X-ray erosion scores (ES) on clinical response and future radiological damage over 1 yr in different groups of pts from AVERT-2. Methods: BL and Wk 52 X-ray data were evaluated using Sharp/van der Heijde score. SDAI remission rates (RRs; ≤3.3), unadjusted mean changes from BL (CfB) and duration of/time to sustained remission over 52 wks were evaluated. Radiographic progression was assessed at Wk 52 using CfB in ES. A range of BL ES cut-offs were evaluated to highlight key findings through comparison of pts with low and high ES. Results: Of 994 pts in the study, 964 (97%) had BL (median 2.0, interquartile range [IQR] 0.5–5.1) and 792 (80%) had BL and Wk 52 (median 2.5, IQR 1.0–6.5) ES. Results in Table 1 are based on ES cut-offs of 2 and 5, resulting in 53% and 75%, respectively, of pts in low ES groups. In pts who received ABA+MTX, those with low ES had higher SDAI RRs over 52 wks vs pts with high ES. The relationship was more pronounced for higher cut-offs. This was not observed with ABA placebo+MTX (MTX). Greater reduction of mean CfB in SDAI was achieved in pts with high vs low ES who received ABA+MTX. This was not observed with MTX. Pts who received ABA+MTX had longer duration and shorter time to sustained SDAI remission vs MTX. With ABA+MTX, pts with low ES had longer duration and shorter time to sustained SDAI remission vs high ES. This was not observed with MTX. Mean CfB in ES at Wk 52 was lower in the ABA+MTX arm vs the MTX arm. ABA seemed to equally protect pts with low and high ES; with MTX, pts with high ES had higher mean CfB in ES at Wk 52 than pts with low ES. Conclusion: This erosion-based stratification of the AVERT-2 early seropositive RA population emphasizes the importance of treating pts prior to the accumulation of erosive disease. Abatacept+MTX led to higher SDAI RRs in pts with low vs high ES and provided further protection vs MTX alone against future radiological damage in pts with high ES. Additional statistical modelling and adjustment for confounding factors at BL is warranted. References: [1]van Nies JAB, et al. Ann Rheum Dis 2015;74:883–9. [2]Emery P, et al. ACR/ARHP 2018; Chicago, USA:abstract 563. Acknowledgments: Fiona Boswell (editorial assistance, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: Chahin Pachai Employee of: Bristol-Myers Squibb, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Jessica Landis Employee of: Bristol-Myers Squibb, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Vivian Bykerk: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Shuyan Du Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Wendy Hayes Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Chun Wu Employee of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor)

  • fri0090 maintenance of clinical response with abatacept in combination with mtx in individual patients with early ra who are mtx naive and anti citrullinated Protein Antibody acpa results from the induction period of avert 2 a randomised phase iiib study
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: Paul Emery, T W J Huizinga, Yoshiya Tanaka, V P Bykerk, Gustavo Citera, Clifton O Bingham, Sean E Connolly, K H G Huang, Y Elbez, R Wong
    Abstract:

    Background: In the 56-wk induction period (IP) of the Phase IIIb Assessing Very Early RA Treatment (AVERT)-2 trial (NCT02504268), more patients (pts) achieved SDAI remission (≤3.3) with abatacept (ABA) + MTX vs ABA placebo (PBO) + MTX at IP Wk 52.1 It is unknown whether each individual pt within a treatment (Tx) group achieves and sustains the same efficacy endpoints at all time points during the IP. Objectives: To investigate whether ABA effectiveness is sustained by individual pts who achieved SDAI remission (≤3.3), SDAI low disease activity (LDA; >3.3–11), DAS28 (CRP) Methods: Pts were randomised 3:2 to blinded SC ABA (125 mg/wk) + MTX or ABA PBO + MTX induction Tx for 56 wks. Key inclusion criteria: age ≥18 yrs; RA diagnosis (ACR/EULAR 2010 criteria); RA duration ≤6 mos; SDAI >11; ACPA+; CRP >3 mg/L or ESR ≥28 mm/h; TJC ≥3 and SJC ≥3; DMARD naive. Response rates were investigated by Tx arm in the cohort 1 analysis population (all randomised pts treated in the IP [intent-to-treat analysis]). Results: Of randomised cohort 1, 752 pts were treated during the IP: 451 with ABA + MTX and 301 with ABA PBO + MTX. Baseline characteristics were similar across Tx arms.1 Stringent SDAI remission endpoint at IP Wk 24 was achieved by 22% of ABA + MTX-treated pts; of these, 56% sustained SDAI remission at IP Wks 40/52 (Table). A similar proportion of ABA + MTX-treated pts achieved (17%) and sustained (58%) Boolean remission at IP Wks 24 and 40/52. At IP Wk 24, 42% of ABA + MTX-treated pts achieved DAS28 (CRP) Conclusion: The majority of individual pts with RA who achieved clinically stringent endpoints such as SDAI remission, DAS28 (CRP) References: [1]Emery P, et al. ACR 2018; San Diego, USA: Poster 563. Acknowledgments: Lola Parfitt (medical writing, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Vivian Bykerk: None declared, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Yedid Elbez Consultant of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Karissa Lozenski Employee of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB

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  • sat0104 maintenance of sdai remission and patient reported outcomes pros following dose de escalation of abatacept in mtx naive anti citrullinated Protein Antibody acpa patients with early ra results from avert 2 a randomised phase iiib study
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: Paul Emery, T W J Huizinga, Yoshiya Tanaka, V P Bykerk, Gustavo Citera, Clifton O Bingham, S Banerjee, Sean E Connolly, J Zhuo, R Wong
    Abstract:

    Background: The Phase IIIb Assessing Very Early RA Treatment (AVERT)-2 trial (NCT02504268) evaluated SC abatacept (ABA) + MTX vs ABA placebo (PBO) + MTX in ACPA+ patients (pts) with early, active RA.1 Results from the 56-wk induction period (IP) showed a significantly greater proportion of pts treated with ABA + MTX (vs MTX alone) reported clinically meaningful improvements in HAQ-DI, global disease activity and pain, which were sustained at 52 wks.2 Objectives: To report maintenance of SDAI remission and PROs from the AVERT-2 de-escalation (D-E) period. Methods: Pts received blinded SC ABA (125 mg once wkly [QW]) + MTX or ABA PBO + MTX induction treatment for 56 wks. In this analysis, pts who completed induction with ABA + MTX and had sustained SDAI remission (≤3.3 at Wks 40 and 52) were re-randomised 1:1:1 to ABA QW + MTX, stepwise D-E (ABA every other wk + MTX for 24 wks then ABA PBO + MTX for 24 wks), or ABA QW + MTX PBO for 48 wks in the D-E period. PROs included physical function (HAQ-DI [0–3; decrease=improvement] and Short-Form 36 [SF-36] v2.0 Physical Functioning Scale [PFS]; 0–100; increase=improvement), and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] score; 0–52; decrease=improvement). Endpoints included: proportion of pts in SDAI remission and pts with HAQ-DI response (decrease from IP Day [D]1 in HAQ-DI ≥0.30); adjusted mean change (adMC) from D-E D1 in HAQ-DI, SF-36 PFS or FACIT-F to D-E Wk 48. adMCs were estimated using a mixed effect model with repeated measures. Results: 147 ABA + MTX-treated pts were re-randomised in the D-E period. Across re-randomised arms, the range of mean scores was 1.87–2.52 for SDAI and 0.18–0.30 for HAQ-DI at entry into D-E period (D-E D1). 74% of pts receiving ABA QW + MTX maintained SDAI remission at D-E Wk 48 (Fig 1); this proportion was higher than in the ABA withdrawal and ABA QW + MTX PBO arms. Pts continuing ABA QW + MTX maintained HAQ-DI response during D-E (Fig 1), but by D-E Wk 48 the proportion of pts with HAQ-DI response in the ABA withdrawal arm declined by 30%. At D-E Wk 48, a small numerical decrease (adMC –0.04) in HAQ-DI was observed in the ABA QW + MTX arm; increases were seen in the withdrawal (adMC 0.26) and ABA QW + MTX PBO arms (adMC 0.16). By D-E Wk 48, SF-36 PFS increased (adMC 1.68) in the ABA QW + MTX arm but decreased in the withdrawal (adMC –3.34) and ABA QW + MTX PBO (adMC –1.45) arms. FACIT-F score increased during D-E in all arms, but the increase at D-E Wk 48 was lower in the ABA QW + MTX arm (adMC 0.79) vs the withdrawal (adMC 4.12) and ABA QW + MTX PBO (adMC 2.41) arms. Similar trends were seen for other PROs including Work Productivity and Activity Impairment-RA; while activity impairment remained stable in the ABA QW + MTX arm, there was a trend for worsening in the withdrawal arm. Conclusion: In the AVERT-2 D-E period, continued combination therapy (abatacept + MTX) resulted in maintenance of benefits on PROs, particularly physical functioning, in seropositive pts with early RA. D-E of abatacept followed by complete withdrawal was associated with the greatest loss of remission as well as worsening of PROs. The PRO results corresponded well to the maintenance of clinical (SDAI) remission. References: [1]Emery P, et al. ACR 2018; San Diego, USA: Poster 563. [2]Emery P, et al. ACR 2019; Atlanta, USA: Poster 1423. Acknowledgments: Joanna Wright (medical writing, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Vivian Bykerk: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Subhashis Banerjee Shareholder of: AbbVie, Bristol-Myers Squibb, Lily, Pfizer, Employee of: Bristol-Myers Squibb (current); AbbVie, Lily, Pfizer (past), Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Karissa Lozenski Employee of: Bristol-Myers Squibb, Yedid Elbez Consultant of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB

  • thu0095 impact of baseline erosion score on response to treatment and future radiological damage in avert 2 a randomised phase iiib study of abatacept in mtx naive anti citrullinated Protein Antibody positive acpa patients with early ra
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: C Pachai, T W J Huizinga, Yoshiya Tanaka, V P Bykerk, Gustavo Citera, Clifton O Bingham, Sean E Connolly, R Wong, J Landis, K H G Huang
    Abstract:

    Background: Bone erosions are associated with poor prognosis in patients (pts) with RA. They can be associated with subclinical inflammation and independently predict future radiological damage.1 The Phase IIIb Assessing Very Early RA Treatment (AVERT)-2 (NCT02504268) trial evaluated abatacept (ABA)+MTX in MTX-naive, ACPA+ pts with early RA.2 Objectives: To explore the impact of baseline (BL) X-ray erosion scores (ES) on clinical response and future radiological damage over 1 yr in different groups of pts from AVERT-2. Methods: BL and Wk 52 X-ray data were evaluated using Sharp/van der Heijde score. SDAI remission rates (RRs; ≤3.3), unadjusted mean changes from BL (CfB) and duration of/time to sustained remission over 52 wks were evaluated. Radiographic progression was assessed at Wk 52 using CfB in ES. A range of BL ES cut-offs were evaluated to highlight key findings through comparison of pts with low and high ES. Results: Of 994 pts in the study, 964 (97%) had BL (median 2.0, interquartile range [IQR] 0.5–5.1) and 792 (80%) had BL and Wk 52 (median 2.5, IQR 1.0–6.5) ES. Results in Table 1 are based on ES cut-offs of 2 and 5, resulting in 53% and 75%, respectively, of pts in low ES groups. In pts who received ABA+MTX, those with low ES had higher SDAI RRs over 52 wks vs pts with high ES. The relationship was more pronounced for higher cut-offs. This was not observed with ABA placebo+MTX (MTX). Greater reduction of mean CfB in SDAI was achieved in pts with high vs low ES who received ABA+MTX. This was not observed with MTX. Pts who received ABA+MTX had longer duration and shorter time to sustained SDAI remission vs MTX. With ABA+MTX, pts with low ES had longer duration and shorter time to sustained SDAI remission vs high ES. This was not observed with MTX. Mean CfB in ES at Wk 52 was lower in the ABA+MTX arm vs the MTX arm. ABA seemed to equally protect pts with low and high ES; with MTX, pts with high ES had higher mean CfB in ES at Wk 52 than pts with low ES. Conclusion: This erosion-based stratification of the AVERT-2 early seropositive RA population emphasizes the importance of treating pts prior to the accumulation of erosive disease. Abatacept+MTX led to higher SDAI RRs in pts with low vs high ES and provided further protection vs MTX alone against future radiological damage in pts with high ES. Additional statistical modelling and adjustment for confounding factors at BL is warranted. References: [1]van Nies JAB, et al. Ann Rheum Dis 2015;74:883–9. [2]Emery P, et al. ACR/ARHP 2018; Chicago, USA:abstract 563. Acknowledgments: Fiona Boswell (editorial assistance, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: Chahin Pachai Employee of: Bristol-Myers Squibb, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Jessica Landis Employee of: Bristol-Myers Squibb, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Vivian Bykerk: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Shuyan Du Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Wendy Hayes Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Chun Wu Employee of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor)

  • fri0090 maintenance of clinical response with abatacept in combination with mtx in individual patients with early ra who are mtx naive and anti citrullinated Protein Antibody acpa results from the induction period of avert 2 a randomised phase iiib study
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: Paul Emery, T W J Huizinga, Yoshiya Tanaka, V P Bykerk, Gustavo Citera, Clifton O Bingham, Sean E Connolly, K H G Huang, Y Elbez, R Wong
    Abstract:

    Background: In the 56-wk induction period (IP) of the Phase IIIb Assessing Very Early RA Treatment (AVERT)-2 trial (NCT02504268), more patients (pts) achieved SDAI remission (≤3.3) with abatacept (ABA) + MTX vs ABA placebo (PBO) + MTX at IP Wk 52.1 It is unknown whether each individual pt within a treatment (Tx) group achieves and sustains the same efficacy endpoints at all time points during the IP. Objectives: To investigate whether ABA effectiveness is sustained by individual pts who achieved SDAI remission (≤3.3), SDAI low disease activity (LDA; >3.3–11), DAS28 (CRP) Methods: Pts were randomised 3:2 to blinded SC ABA (125 mg/wk) + MTX or ABA PBO + MTX induction Tx for 56 wks. Key inclusion criteria: age ≥18 yrs; RA diagnosis (ACR/EULAR 2010 criteria); RA duration ≤6 mos; SDAI >11; ACPA+; CRP >3 mg/L or ESR ≥28 mm/h; TJC ≥3 and SJC ≥3; DMARD naive. Response rates were investigated by Tx arm in the cohort 1 analysis population (all randomised pts treated in the IP [intent-to-treat analysis]). Results: Of randomised cohort 1, 752 pts were treated during the IP: 451 with ABA + MTX and 301 with ABA PBO + MTX. Baseline characteristics were similar across Tx arms.1 Stringent SDAI remission endpoint at IP Wk 24 was achieved by 22% of ABA + MTX-treated pts; of these, 56% sustained SDAI remission at IP Wks 40/52 (Table). A similar proportion of ABA + MTX-treated pts achieved (17%) and sustained (58%) Boolean remission at IP Wks 24 and 40/52. At IP Wk 24, 42% of ABA + MTX-treated pts achieved DAS28 (CRP) Conclusion: The majority of individual pts with RA who achieved clinically stringent endpoints such as SDAI remission, DAS28 (CRP) References: [1]Emery P, et al. ACR 2018; San Diego, USA: Poster 563. Acknowledgments: Lola Parfitt (medical writing, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Vivian Bykerk: None declared, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Yedid Elbez Consultant of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Karissa Lozenski Employee of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB