1249 - Number of Cardiovascular Risk Factors May be Associated with Higher Disease Activity Severity. Exploratory Analysis of Baseline Data from the Canadian Methotrexate and Etanercept Outcome Study: A Randomized Trial of Etanercept and Methotrexate vs Etanercept Alone in Rheumatoid Arthritis

Monday, November 7, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Janet Pope, Univ of Western Ontario, London, ON, Edward Keystone, University of Toronto, Toronto, ON, Boulos Haraoui, Institut de Rhumatologie, Montreal, QC, J. Carter Thorne, Southlake Regional Health Centre, Newmarket, Newmarket, ON and Melanie Poulin-Costello, Amgen Canada Inc., Mississauga, ON
Presentation Number: 1249

Background/Purpose:

We designed a real-world rheumatoid arthritis (RA) non-inferiority trial to compare the proportion of patients with low disease activity while on etanercept (ETN) monotherapy vs ETN + methotrexate (MTX). The trial is still ongoing. Baseline data were explored to determine if cardiovascular (CV) risk factors such as hypertension (HTN), diabetes mellitus (DM), hypercholesterolemia, prior myocardial infarction (MI), and high body mass index (BMI) correlate with higher baseline disease activity. Two studies suggest increased erosions in those with low BMI in early RA.1,2

Method:

Baseline characteristics of established RA patients who, despite MTX therapy, had active disease (≥ 3 swollen joints), DAS28 ≥ 3.2, and were TNF inhibitor naïve were studied. A post-hoc exploratory analysis of baseline data examined the impact of CV risks on baseline DAS, adjusting for sex, age, prior RA medications, and duration of disease, using analysis of variance (ANOVA). Model selection was done by backwards elimination for p < 0.1.

Result:

258 patients with active RA (76% female; mean age, 54.7 ± 12.5 yrs; DAS28, 5.4 ± 1.1; duration of RA, 8.9 ± 8.4 yrs) were enrolled. Mean baseline health assessment questionnaire (HAQ) score was 1.38 ± 0.61. Mean duration of MTX treatment was 4.9 ± 4.7 yrs (mean dose, 20.5 ± 4.1 mg/wk). Higher baseline disease activity was statistically correlated with an increased number of CV risk factors (p < 0.0001), although each CV risk was not significant. No other factors had a significant statistical correlation with DAS28. In addition, BMI and DAS were not related statistically.

Limitations:

Data on smoking and family history of CV events were not collected, and CV risk was determined from patient medical history. Only patients with active disease were selected for the study; which could bias the results compared to a prevalent RA population. Our study size is small and this was a post-hoc analysis, however numerically (but not statistically) it appears that many CV risk factors were associated with higher DAS.

 

Table 1: Cardiovascular Comorbidities and Disease Activity at Baseline

Comorbidity

Total Population (N = 258)

n

Mean DAS28 (95% CI)

Number of CV risk factors*, p = 0.0002a

 

 

0

116

5.1 (4.9, 5.3)

1

75

5.6 (5.3, 5.8)

2

41

5.7 (5.4, 6.0)

³ 3

26

6.0 (5.6, 6.4)

Gender, p = 0.0678

 

 

Female

197

5.5 (5.3, 5.6)

Male

61

5.2 (4.9, 5.5)

Diabetes Mellitus, p = 0.2481

 

 

Yes

18

5.7 (4.9, 6.5)

No

239

5.4 (5.3, 5.5)

Hypertension, p = 0.1417

 

 

Yes

81

5.8 (5.6, 6.0)

No

154

5.2 (5.0, 5.4)

Hypercholesterolemia, p = 0.9254

 

 

Yes

43

5.7 (5.4, 6.0)

No

215

5.4 (5.2, 5.5)

Myocardial infarction, p = 0.7403

 

 

Yes

11

5.9 (4.9, 6.8)

No

247

5.4 (5.3, 5.5)

BMI, kg/m², p = 0.3057b

 

 

< 18.5

5

5.9 (5.4, 6.4)

³ 18.5 to < 25

59

5.3 (5.0, 5.6)

³ 25 to < 30

74

5.3 (5.1, 5.5)

³ 30

63

5.8 (5.5, 6.1)

Other CV medical history, p = 0.5820

 

 

Yes

27

5.6 (5.2, 6.0)

No

231

5.4 (5.3, 5.5)

Elevated CRPc

 

 

³ 3 mg/L

173

5.6 (5.4, 5.8)

< 3 mg/L

51

4.7 (4.5, 4.9)

ap-values from the multivariate ANOVA backwards elimination results. Age, duration of disease, and duration of methotrexate were also included in the model (p > 0.10) but are not shown here.

bBMI was a continuous variable in the ANOVA

cNot included in the ANOVA

*CV risk factors: hypertension, hypercholesterolemia, diabetes, prior MI, BMI ³ 30

Hypercholesterolemia includes dyslipidemia and high cholesterol

27 subjects had 46 cardiac-related medical histories including: angina attack, angina pectoris, angioplasty, cardiac catheterization, cardiovascular disease, carotid artery stenosis, carotid endarterectomy, coronary artery bypass graft, coronary arterial stent insertion, dyslipidemia (resolved at time of study start), hypertension (resolved at time of study start), ischemia, myocardial infarction, stent placement

Abbreviations: ANOVA = analysis of variance; BMI = body mass index; CI = confidence interval; CRP = C-reactive protein; CV = cardiovascular; MI = myocardial infarction

 

Conclusion:

There is a statistical suggestion from this baseline data that an increase in the number of CV risks were associated with worse baseline DAS28 scores in this clinical trial of patients with active RA.

References:

1.    Velpula U, et al. J Rheumatol. 2011;38(3):434-8. Epub 2010 Nov 15.

2.    Kaufmann J, et al. J Rheumatol. 2003;30(11):2350-5.

 

Trial Registration: ClinicalTrials.gov, number: NCT00654368

Role of the Study Sponsor

Amgen Canada Inc. oversaw the design, conduct, collection of data in the study and assisted in the analysis and interpretation of data

Acknowledgements

Rose Pirone, MSc, and Jai Sharma, MSc, The Synapse Group, Burlington, Ontario, provided medical writing assistance in the form of drafting and revising as per authors' directions and in accordance with the standards of the International Committee of Medical Journal Editors. Medical writing support was funded by Amgen Canada Inc. and Pfizer Canada

 


Keywords: cardiovascular disease, etanercept, methotrexate (MTX) and rheumatoid arthritis (RA)

Disclosure: J. Pope, Amgen, 2, Amgen and Pfizer, 5 ; E. Keystone, Abbott Laboratories, Amgen Inc; AstraZeneca Pharmaceuticals LP, Bristol-Meyers Squibb, Centocor Inc, F. Hoffmann-LaRoche Inc, Genzyme, Merck, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, UCB, 2, Abbott Laboratories, AstraZeneca Pharmaceuticals LP, Biotest, Bristol-Meyers Squibb, Centocor Inc, F. Hoffmann-LaRoche Inc, Genentech Inc, Merck, Nycomed, Pfizer Pharmaceuticals, UCB, 5, Abbott Laboratories, Bristol-Meyers Squibb, F. Hoffmann-LaRoche Inc, Merck, Pfizer Pharmaceuticals, UCB, 8 ; B. Haraoui, Abbott, Amgen, Bristol-Myers Squibb, Merck, Pfizer, Roche, UCB, 2, 9, Speakers’ Bureau: Abbott, Amgen, Bristol-Myers Squibb, Merck, Pfizer, Roche, UCB, 8, Speakers’ Bureau: Abbott, Amgen, Bristol-Myers Squibb, Merck, Pfizer, Roche, UCB, 9 ; J. C. Thorne, Amgen, Pfizer, Abbott, Bristol-Myers Squibb, Roche, UCB, Merck, 5, Amgen, Pfizer, Abbott, Bristol-Myers Squibb, Roche, UCB, Merck,, 2, Centocor, Inc., 9 ; M. Poulin-Costello, Amgen, 3 .