ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2486

Patient-Reported Outcomes Following 12 Months of Therapy with Abatacept (Plus Methotrexate or as Monotherapy) or Methotrexate and up to 6 Months after Treatment Withdrawal in Patients with Early Rheumatoid Arthritis

Daniel E. Furst1, Vivian P. Bykerk2, Gerd Burmester3, B Combe4, T W J Huizinga5, E Alemao6, D Wong6, C S Karyekar6 and P Emery7, 1University of California at Los Angeles, Los Angeles, CA, 2Hospital for Special Surgery, Weill Cornell Medical College, New York, NY, 3Charité – University Medicine Berlin, Berlin, Germany, 4Monpellier University Hospital, Montpellier, France, 5Leiden University Medical Center, Leiden, Netherlands, 6Bristol-Myers Squibb, Princeton, NJ, 7University of Leeds, Leeds, United Kingdom

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Therapeutic Strategies, Biomarkers and Predictors of Outcomes in Rheumatoid Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Early biologic use can improve long-term control of RA,1,2 potentially leading to improved physical function and reduced pain. Recent EULAR recommendations support shared decisions between the patient (pt) and rheumatologist,3 emphasizing the need for more pt-focused outcomes to assess treatment targets. In the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial, greater % of pts achieved DAS28 (CRP) <2.6 after 12 mths of treatment with SC abatacept (ABA) + MTX and 6 mths after withdrawal of all RA therapy, compared with MTX alone. At most time points, ABA monotherapy was more effective than MTX alone in controlling signs and symptoms of RA.4 Here, pt-reported outcomes (PROs) are presented over 18 mths (12 mths of treatment and 6 mths after withdrawal of all RA therapy) in the AVERT trial.

 

Methods: AVERT enrolled pts who were MTX naïve, anti-cyclic citrullinated peptide 2 seropositive (CCP2+), aged ≥18 yrs, with active synovitis ≥2 joints for ≥8 wks, DAS28 (CRP) ≥3.2, and a disease onset of ≤2 yrs. Pts were randomized to 12 mths of weekly SC ABA (125 mg) + MTX, SC ABA (125 mg) + placebo or MTX + placebo. All RA treatment was removed after 12 mths (ABA immediately and MTX and steroids tapered over 1 mth) in pts with DAS28 (CRP) <3.2. Fatigue was measured by 100-mm visual analog scale, physical function by HAQ-DI, and health-related quality of life by Short Form-36 (SF-36; Bodily Pain, Physical and Mental Component Summary subscores [PCS and MCS] presented). Improvement in activity limitation and work productivity/activity were estimated using the Activity Limitation Questionnaire (APaQ) and Work Productivity Activity Impairment Questionnaire (WPAI:RA). Adjusted mean change from baseline in PROs was calculated using a longitudinal repeated measures model.

 

Results: 351 pts with early RA were enrolled (n=119, ABA + MTX; n=116, ABA monotherapy; n=116, MTX monotherapy; at baseline: mean disease duration 0.6 yrs, mean DAS28 (CRP) 5.4, mean HAQ-DI 1.4, 95.2% RF+ and anti-CCP2+). Adjusted mean changes in PROs during treatment (baseline to Mth 12) and treatment withdrawal (Mth 12 to Mth 18) are presented (Table).

 

Adjusted mean change in PROs (95% CI)

Outcome

Baseline to Mth 12

 (Treatment period)

Mth 12 to Mth 18*

(Treatment withdrawal) 

 

Abatacept + MTX

Abatacept monotherapy

MTX

Abatacept + MTX

Abatacept monotherapy

MTX

Fatigue, 100 mm VAS

n=81; –34.9†
(–39.8, –29.9)

n=82; –26.1
(–31.2, –20.9)

n=80; –26.7
(–32.1, –21.4)

n=43; 17.2
(9.2, 25.3)

n=36; 10.8
(1.5, 20.2)

n=33; 13.3
(4.6, 21.9)

HAQ-DI

n=90; –0.87
(–0.99, –0.76)

n=82; –0.73
(–0.85, –0.61)

n=77; –0.72
(–0.85, –0.60)

n=35; 0.36
(0.16, 0.55)

n=29; 0.25
(0.04, 0.46)

n=25; 0.39
(0.17, 0.61)

SF-36

Bodily
pain

n=94

36.5
(31.9, 41.2)

n=88

29.4
(24.6, 34.2)

n=91

30.8
(26.1, 35.6)

n=48

–22.6
(–30.4, –14.8)

n=40

–14.8
(–23.6, –5.9)

n=37

–17.4
(–26.2, –8.7)

PCS

13.9†
(12.1, 15.8)

10.2
(8.3, 12.1)

10.9
(9.1, 12.8)

–7.8
(–10.5, –5.0) 		–5.7
(–8.8, –2.5) 		–4.7
(–7.8, –1.5)

MCS

7.7
(5.6, 9.7)

5.5
(3.4, 7.6)

7.2
(5.2, 9.3)

–4.9
(–8.1, –1.8) 		–1.1
(–4.7, 2.4) 		–5.0
(–8.5, –1.5)

Activity limitation, days

n=82; –8.7
(–10.0, –7.4)

n=74; –6.2
(–7.5, –4.9)

n=71; –7.9
(–9.3, –6.6)

n=44; 3.5
(0.7, 6.2)

n=36; 2.9
(–0.4, 6.1)

n=33; 3.7
(0.8, 6.7)

WPAI, %

Work time
missed

n=39; –7.7%
(–14.26, –1.18)

n=35; –4.8%
(–11.56, 1.89)

n=29; –1.0%
(–8.44, 6.45)

n=25; 3.1%
(–7.4, 13.6)

n=18; 4.9%
(–7.8, 17.6)

n=12; 3.8%
(–10.8, 18.4)

Impairment
while working

n=36; –28.8%
(–36.0, –21.6)

n=34; –24.1%
(–31.3, –16.9)

n=26; –22.3%
(–30.7, –14.0)

n=25; 16.8%
(5.2, 28.4) 		n=18; 11.1%
(–2.2, 24.4) 		n=12; 10.5%
(–4.8, 25.8)

Overall work impairment

n=36; –23.3%
(–29.7, –17.0)

n=34; –19.2%
(–25.5, –12.8)

n=26; –17.4%
(–24.7, –10.0)

n=25; 12.7%
(2.3, 23.2) 		n=18; 8.0%†
(–3.9, 20.0) 		n=12; 4.2%
(–9.6, 17.9)

Activity impairment

n=82; –31.0%
(–35.8, –26.1)

n=74; –27.7%
(–32.8, –22.7)

n=71; –27.8%
(–33.0, –22.6)

n=44; 15.4%
(6.5, 24.2) 		n=36; 11.1%
(0.7, 21.4) 		n=33; 13.5%
(4.0, 23.1)

MCS, Mental Component Summary subscore; PCS, Physical Component Summary subscore; SF-36, Short Form-36;
VAS, visual analog scale; WPAI, Work Productivity Activity Impairment Questionnaire.

*Pts with assessments available at both Mth 12 and Mth 18.

†p<0.05 for treatment difference vs MTX (95% CI for the estimate of treatment difference did not cross 0).

Conclusion: In pts with early RA, abatacept + MTX, abatacept monotherapy and MTX alone showed improvements in PROs, with greater improvements seen for abatacept + MTX at 12 mths, compared with MTX alone. PROs worsened in all groups after treatment withdrawal but remained below baseline values. These results indicate that treatment with abatacept + MTX early in the course of RA leads to notable improvements in outcomes that are important to pts, such as fatigue, physical function, pain and participation in daily activities, and that some improvement may be maintained up to 6 mths following treatment withdrawal.

References:

1.    Westhovens R, et al. Ann Rheum Dis 2009;68:1870–7.

2.    Emery P, et al. Ann Rheum Dis 2010;69:510–6.

3.    Smolen JS, et al. Ann Rheum Dis 2014;73:492–509.

4.    Emery P, et al. Ann Rheum Dis 2014;73:OP0026.

 

Disclosure:

D. E. Furst,

AbbVie, Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB,

2,

AbbVie, Actelion, Amgen, BMS, Cytori, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB,

5,

AbbVie, Actelion, UCB ,

8;

V. P. Bykerk,

Amgen, Pfizer, BMS, Janssen, UCB, Roche/Genentech,

2;

G. Burmester,

AbbVie, Pfizer, Roche, UCB,

2,

AbbVie, BMS, MSD, Medimmune, Novartis, Pfizer, Roche, Sandoz, UCB,

5,

AbbVie, BMS, MSD, Pfizer, Roche, Sandoz, UCB,

8;

B. Combe,

Pfizer, Roche-Chugai,

2,

BMS, Merck, Pfizer, Roche-Chugai, UCB,

8;

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,

Meteor Board,

6,

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;

E. Alemao,

BMS,

3,

BMS,

1;

D. Wong,

Bristol-Myers Squibb,

1,

Bristol-Myers Squibb,

3;

C. S. Karyekar,

Bristol-Myers Squibb,

3;

P. Emery,

AbbVie, BMS, Merck, Pfizer, Roche, Takeda,

5,

AbbVie, BMS, Merck, Pfizer, Roche,

2.

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