ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 563

Efficacy and Safety of Abatacept in Combination with MTX in Early, MTX-Naïve, Anti-Citrullinated Protein Antibody–Positive Patients with RA: Primary and 1-Year Results from a Phase IIIb Study

Paul Emery1, Yoshiya Tanaka2, Vivian P. Bykerk3, Tom W.J. Huizinga4, Gustavo Citera5, Marleen Nys6, Sean E. Connolly7, Alyssa Johnsen7 and Roy Fleischmann8, 1University of Leeds and Leeds Musculoskeletal Biomedical Research Unit, Leeds, United Kingdom, 2University of Occupational and Environmental Health, Kitakyushu, Japan, 3Hospital for Special Surgery, New York, NY, 4Leiden University Medical Center, Leiden, Netherlands, 5Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, 6Bristol-Myers Squibb, Braine L’Alleud, Belgium, 7Bristol-Myers Squibb, Princeton, NJ, 8Metroplex Clinical Research Center, Dallas, TX

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Date: Sunday, October 21, 2018

Title: Rheumatoid Arthritis – Treatments Poster I: Strategy and Epidemiology

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: In patients (pts) with early (disease duration ≤24 months [mths]), MTX-naïve RA and poor prognostic factors including anti-citrullinated protein antibody (ACPA) positivity (+), abatacept (ABA) + MTX vs MTX was superior at achieving DAS28 (CRP) <2.6 at 12 mths.1,2 The AVERT-2 trial (clinicaltrials.gov, NCT02504268) further investigates the ability of ABA + MTX to induce validated metrics of remission in pts with ACPA+ early RA (disease duration ≤6 mths).

Methods: Pts were randomized (3:2) to double-blind, weekly SC ABA 125 mg + MTX vs MTX for 56 weeks (wks). Key inclusion criteria: age ≥18 years; RA diagnosis ≤6 mths (ACR/EULAR 2010 criteria); ACPA+; TJC and SJC ≥3; CRP >0.3 mg/dL (ULN)/ESR ≥28 mm/h; SDAI >11; DMARD naïve. Primary endpoint: proportion of pts in SDAI remission (SDAI ≤3.3) at Wk 24 in the first 375 pts randomized (primary analysis population). Hierarchically tested secondary endpoints: DAS28 (CRP) <2.6 at Wk 24 and SDAI ≤3.3 at Wk 52 (primary analysis population), and change from baseline (CfB) in total Sharp/van der Heijde score (SHS; X ray) and Boolean remission at Wk 52 (all randomized pts). Comparisons were made using logistic regression for binary outcomes and rank-based non-parametric analysis of covariance for X ray data.

Results: In the primary analysis population, 225 pts received ABA + MTX and 150 received MTX. Overall, 752 pts were randomized to ABA + MTX (n=451) and MTX (n=301); 63 and 68 discontinued, respectively, by Wk 52. Baseline characteristics were similar across treatment arms in each population (Table 1). The proportion of pts achieving SDAI ≤3.3 at Wk 24 was 21.3% for ABA + MTX and 16.0% for MTX (primary analysis population; p=0.2359; Table 2). Nominally significant benefits in favor of ABA + MTX were observed for all secondary endpoints including mean CfB in total SHS at Wk 52 in all randomized pts (0.5 vs 2.5; nominal p<0.0001; Table 2). Safety profiles were similar across treatment arms; no new safety signals were identified.

Conclusion: Abatacept + MTX vs MTX in ACPA+, early RA did not meet the primary endpoint of a statistically significant difference in SDAI ≤3.3 at Wk 24 in the primary analysis population, but did so at Wk 52. Consistent with previous studies,1,2 the benefits of abatacept + MTX vs MTX were seen for the composite endpoint of DAS28 (CRP) <2.6 at Wk 24 in the primary analysis population, and for the other secondary endpoints in all randomized pts.

References:

  1. Emery P, et al. Ann Rheum Dis 2015;74:19–26.
  2. Westhovens R, et al. Ann Rheum Dis 2009;68:1870–7.

Medical writing assistance provided by Sharon Gladwin, PhD (Caudex), funded by Bristol-Myers Squibb.

Table 1. Baseline Characteristics

Primary analysis population (n=375)

All randomized patients
(n=752)

ABA + MTX
(n=225)

MTX monotherapy
(n=150)

ABA + MTX
(n=451)

MTX monotherapy
(n=301)

Age, years

50 (13)

50 (15)

49 (13)

49 (14)

Female, n (%)

170 (75.6)

121 (80.7)

349 (77.4)

243 (80.7)

RA duration, months

1.3 (1.5)

1.3 (1.4)

1.2 (1.4)

1.3 (1.4)

TJC (28 joints)

13.8 (7.0)

13.4 (6.7)

13.2 (6.8)

13.7 (6.8)

SJC (28 joints)

10.4 (6.0)

11.1 (5.9)

10.0 (5.7)

10.7 (5.9)

Pain

66.2 (21.4)

65.6 (22.6)

66.5 (22.5)

65.4 (22.4)

HAQ-DI

1.6 (0.7)

1.6 (0.6)

1.6 (0.7)

1.6 (0.7)

Patient Global Assessment

65.3 (21.5)

63.0 (23.7)

65.7 (22.7)

62.7 (24.1)

Physician Global Assessment

66.3 (18.4)

66.4 (20.6)

65.1 (18.5)

66.1 (19.8)

RF+, n (%)

210 (93.3)

136 (90.7)

420 (93.1)

279 (92.7)

CRP, mg/dL

2.3 (3.1)

1.9 (2.1)

2.0 (2.7)

1.9 (2.2)

DAS28 (CRP)

5.7 (1.1)

5.6 (1.0)

5.6 (1.1)

5.6 (1.0)

SDAI

39.6 (14.7)

39.6 (14.1)

38.2 (14.1)

39.4 (13.8)

Total SHS

NC

NC

9.8 (16.3)

13.0 (19.8)

CS* at Day 1, n (%)

96 (42.7)

52 (34.7)

208 (46.1)

93 (30.9)

Data are mean (SD) unless otherwise indicated
Pain and Patient and Physician Global Assessment were measured by visual analog scale (0–100 mm)

*Oral and/or injectable
CS=corticosteroids; NC=not calculated; SHS=Sharp/van der Heijde score

Table 2. Primary and Secondary Efficacy Endpoints

ABA + MTX

MTX monotherapy

Adjusted OR* (95% CI)

p value

SDAI ≤3.3 at 24 weeks (primary analysis population)

21.3 (48/225)

16.0
(24/150)

1.4 (0.8, 2.5)

0.2359

DAS28 (CRP) <2.6 at 24 weeks (primary analysis population)

38.7 (87/225)

25.3 (38/150)

1.9 (1.2, 3.1)

0.0112†

SDAI ≤3.3 at 52 weeks (primary analysis population)

29.8 (67/225)

15.3 (23/150)

2.3 (1.4, 4.0)

0.0021†

Mean (SD) CfB in total SHS at 52 weeks (all randomized)

0.5 (2.3) n=450

2.5 (6.2) n=300

–

<0.0001†

Boolean remission at 52 weeks (all randomized)

21.5 (97/451)

11.6 (35/301)

2.1 (1.4, 3.2)

0.0006†

Data are % (n/N) unless otherwise indicated

For binary outcomes, patients with missing values due to discontinuation or other reasons and those who took a high dose of corticosteroids within 42 days of the 12-month assessment were imputed as non-remitters
For CfB in total SHS, imputation was performed by linear extrapolation for patients with available data at baseline and the time of discontinuation
*Based on logistic regression and adjusted for treatment arm, Japan vs rest of world (yes/no) and baseline measure
†Nominal p value only as the primary endpoint in the statistical hierarchy did not reach significance
CfB=change from baseline; OR=odds ratio; SHS=Sharp/van der Heijde score

Disclosure: P. Emery, Bristol-Myers Squibb, AbbVie, Pfizer, MSD, Novartis, Roche and UCB, 5,AbbVie, Bristol-Myers Squibb, Pfizer, MSD and Roche, 2; Y. Tanaka, Mitsubishi-Tanabe, Bristol-Myers Squibb, Eisai, Chugai, Takeda, AbbVie, Astellas, Daiichi-Sankyo, Ono, MSD, Taisho-Toyama, 2,Daiichi-Sankyo, Astellas, Eli Lilly, Chugai, Sanofi, AbbVie, YL Biologics, Bristol-Myers Squibb, GSK, UCB, Mitsubishi-Tanabe, Novartis, Eisai, Takeda, Janssen, Asahi Kasei, 8; V. P. Bykerk, Amgen, Pfizer, Bristol-Myers Squibb, UCB, Roche, Regeneron, 5,Amgen, Bristol-Myers Squibb, 2; T. W. J. Huizinga, Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Crescendo Bioscience, Inc, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough, UCB, Inc., Eli Lilly, 5,EU & Dutch Arthritis Foundation, 2,Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough, 8,Abbott Laboratories, Roche, 9; G. Citera, Bristol-Myers Squibb, Pfizer, AbbVie, Roche, Eli Lilly, Genzyme, 5; M. Nys, Bristol-Myers Squibb, 1, 3; S. E. Connolly, Bristol-Myers Squibb, 1, 3; A. Johnsen, Bristol-Myers Squibb, 1, 3; R. Fleischmann, AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, EMD-Serano, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB, 2,AbbVie, ACEA, Amgen, Bristol-Myers Squibb, GSK, Eli Lilly, Novartis, Pfizer, Sanofi-Genzyme, UCB, 5.

To cite this abstract in AMA style:

Emery P, Tanaka Y, Bykerk VP, Huizinga TWJ, Citera G, Nys M, Connolly SE, Johnsen A, Fleischmann R. Efficacy and Safety of Abatacept in Combination with MTX in Early, MTX-Naïve, Anti-Citrullinated Protein Antibody–Positive Patients with RA: Primary and 1-Year Results from a Phase IIIb Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/efficacy-and-safety-of-abatacept-in-combination-with-mtx-in-early-mtx-naive-anti-citrullinated-protein-antibody-positive-patients-with-ra-primary-and-1-year-results-from-a-phase-iiib-study/. Accessed .

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