ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1301

Predictors of Significant Disease Activity Score-28 (Using C-reactive protein) Remission Achieved with Intravenous Golimumab in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy:  Results of the Phase 3, Multicenter, Double-Blind, Placebo-Controlled Trial

Clifton O. Bingham III1, Michael Weinblatt2, Alan Mendelsohn3, Lilianne Kim4, Michael Mack5, Jiandong Lu5, Daniel Baker3 and Rene Westhovens6, 1Department of Medicine, Johns Hopkins University, Baltimore, MD, 2Rheumatology & Immunology, Brigham & Women's Hospital, Boston, MA, 3Immunology, Janssen Research & Development, LLC, Spring House, PA, 4Janssen Research & Development, LLC., Spring House, PA, 5Biostatistics, Janssen Research & Development, LLC., Spring House, PA, 6Rheumatology, University Hospital KU Leuven, Leuven, Belgium

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy

Session Type: Abstract Submissions (ACR)

Predictors of Significant Disease Activity Score-28 (Using C-reactive protein) Remission Achieved with Intravenous Golimumab in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy:  Results of the Phase 3, Multicenter, Double-Blind, Placebo-Controlled Trial

Background/Purpose: To evaluate the efficacy of intravenous(IV) golimumab(GLM) 2mg/kg+ methotrexate(MTX) in patients(pts) with active RA despite MTX in achievement of DAS remission and ACR/EULAR remission.

Methods: Pts (n=592) with active RA (≥6/66 swollen joints, ≥6/68 tender joints, CRP≥1.0mg/dL, RF and/or anti-CCP antibody-positive) despite ≥3months of MTX(15-25mg/wk) participated in this multicenter, randomized, double-blind, placebo(PBO)-controlled phase 3 study. Pts were randomized (2:1) to receive IV GLM 2mg/kg or PBO at wks0&4 and q8wks; all pts continued their stable MTX regimen. Clinical remission was defined by DAS28-CRP score <2.6 (prespecified; not validated) and recently developed ACR/EULAR remission1 using SDAI≤3.3 (post hoc; validated). DAS28-CRP analyses used last-observation-carried-forward.
Results:  Statistically significantly higher DAS28-CRP remission rates were observed with GLM+MTX vs. PBO+MTX at Wk14 (15.4% vs. 4.6%, respectively; p<0.001) and Wk24 (17.7% vs. 5.1%, respectively; p<0.001). Similar trends were seen when remission was defined by a SDAI score ≤3.3 (Wk14: 4.8% vs.1.0%, respectively; p<0.05 and Wk24: 7.3% vs. 2.0%, respectively; p<0.01).  Moderate (approx.10%-15%) increases in Wk24 DAS28-CRP remission rates were observed among subgroups of pts defined by HAQ score <1.625 (24%) vs ≥1.625 (12%), baseline physical Functional Class I (27%) vs Class II and III (17% each), swollen joint count <12 (23%) vs ≥12 (14%), tender joint count <24 (25%) vs ≥24 (11%), and CRP <1.5 mg/dL (29%) vs ≥1.5 mg/dL (15%).

Conclusion: In pts with active RA despite ongoing MTX, IV GLM 2 mg/kg+MTX yielded significantly higher DAS28-CRP remission rates and higher ACR /EULAR remission rates vs PBO at Wk14 and Wk24. Achievement of DAS28-CRP remission appeared to be enhanced in pts with lower levels of baseline physical function impairment and lower joint counts. Confirmation of these hypothesis-generating data are required.

 

Table.  No. (%) of pts achieving DAS28-CRP <2.6 at Wk24 by baseline characteristics*

No. randomized GLM pts

495

Age (yrs):  < 65 / ≥ 65

61/336 (18%)  /  9/59 (15%)

Sex:  Female / Male

58/326 (18%)  /  12/69 (17%)

Body weight (median: 70kg):< 70 kg / ≥ 70 kg

34/198 (17%)  /  36/197 (18%)

Disease duration (median:4.7yrs):<4.7yrs/≥4.7yrs

35/196 (18%)  /  35/199 (18%)

Functional class: I / II / III

9/33 (27%) / 48/284 (17%) / 13/78 (17%)

Rheumatoid factor: Negative/Positive

6/30 (20%)  /  64/365 (18%)

Anti-CCP:  Negative / Positive

6/32 (19%)   /   64/362 (18%)

CRP (mg/dL):  ≤ 1.5 / > 1.5

20/69 (29%)  /  50/326 (15%)

Swollen joint count (median: 12): < 12/ ≥ 12

40/174 (23%) / 30/221 (14%)

Tender joint count (median: 24): <24/≥ 24

48/195 (25%) / 22/200 (11%)

HAQ score (median 1.625): < 1.625 / ≥  1.625

46/193 (24%) / 24/202 (12%)

Oral corticosteroids at baseline: Yes / No

38/251 (16%) / 32/144 (22%)

DMARDs at baseline: Yes / No

38/206 (18%) / 32/189 (17%)

NSAIDs at baseline: Yes / No

57/323 (18%) / 13/72 (18%)

Methotrexate at baseline (mg/wk): <15 / ≥ 15

46/268 (17%) / 24/127 (19%)

* Cutpoints for baseline characteristic subgroups were determined by the median value among patients randomized to GLM+MTX

Ref:  1Felson et al, Arthritis Rheum 2011;63:573–86.

 

Disclosure:

C. O. Bingham III,

Roche, Genentech, Biogen/IDEC,

2,

Roche, Genentech,

5;

M. Weinblatt,

Janssen Research and Development, LLC,

9;

A. Mendelsohn,

Janssen Research & Development, LLC,

3;

L. Kim,

Janssen Research & Development, LLC,

3;

M. Mack,

Janssen Research & Development, LLC,

3;

J. Lu,

Janssen Research & Development, LLC,

3;

D. Baker,

Janssen Research & Development, LLC,

3;

R. Westhovens,

Janssen Research and Development, LLC,

9.

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