Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Reduced Cardiovascular Risk with Use of Methotrexate and Tumor Necrosis Factor- Inhibitors in Patients with Rheumatoid Arthritis.

Bozaite-Gluosniene1,  Rasa, Tang2,  Xiaoqin, Kirchner2,  H. Lester, Antohe3,  Jana L., Morris4,  Stephanie J., Wasko5,  Mary Chester, Bili1,  Androniki

Geisinger Medical Center, Danville, PA
Geisinger Center for Health Research, Danville, PA
Geisinger Health System, Danville, PA
Rose Tree Medical Associates---Riddle Memorial Hos, Danville, PA
West Penn Allegheny Health System, Pittsburgh, PA

Background/Purpose:

Methotrexate (MTX) and tumor necrosis factor (TNF)-a inhibitors have been associated with a reduction of incident coronary artery disease (CAD) in rheumatoid arthritis (RA) patients. Here we examine the independent contribution of each medication on risk of CAD.

Methods:

Using an inception cohort of 1829 RA patients without preexisting CAD, diagnosed between 1/1/2001–3/31/2008 were identified. Patients were classified as users (n=1119) or nonusers (n=710) of MTX and users (n=588) or nonusers (n=1241) of TNF-a inhibitors (etanercept, adalimumab, infliximab). Medication exposure was analyzed in time-varying fashion using medication start and stop dates, allowing patient drug exposure status to change over time. Outcome was incident CAD (ICD-9 410. – 419.99 or cardiac revascularization procedure). Cox proportional hazard regression models were used to estimate the associations on developing incident CAD after adjusting for age, gender, hypertension, hyperlipidemia, diabetes, rheumatoid factor, BMI, blood pressure, LDL, ESR, hydroxychloroquine, MTX, corticosteroid and NSAID use. Exposure to MTX, TNF-a inhibitors and all other variables were treated as time-variant in models.

Results:

In MTX nonusers and users groups, incidence rate (IR) for CAD was 37.5 vs.17.6 events per 1000 person-years (p-y), respectively. Among MTX users, the hazard for incident CAD was 0.54 (95% confidence interval (CI) 0.37, 0.77; p=0.001) compared to nonusers; among those taking MTX for more than 24 months the hazard was 0.33 (95% CI 0.22, 0.50; p<0.001). In TNF-a inhibitors nonusers and users groups, IR for CAD was 32.1 vs.11.8 events per 1000 p-y, respectively. Among TNF-a inhibitor users the hazard for incident CAD was 0.54 (CI 0.30, 0.95; p=0.03) compared to nonusers; among those taking TNF-a inhibitor for more than 24 months hazard was 0.24 (95% CI 0.12, 0.51; p<0.001).

Conclusion:

In this inception RA cohort, the use of MTX or TNF-a inhibitors was independently associated with a 46% reduction in incident CAD compared to nonusers; for MTX or TNF-a inhibitor use for more than 24 months the risk was further decreased by 67% and 76% respectively, raising the possibility that TNF-a inhibitor use offers additional cardioprotective effect in RA patients.

Table. Characteristics of RA patients by methotrexate and TNF-a inhibitors use

 Overall (n = 1829)Methotrexate use*p**TNF-a inhibitors use*
Ever (n=1119)Never (n=710)Ever (n=588)Never (n=1241)p**   
N (%)
Male526 (28.8%)297 (26.5%)229 (32.3%).009170 (28.9%)356 (28.7%).921
White1732 (94.7%)1053 (94.1%)679 (95.6%).154552 (93.9%)1180 (95.1%).282
RF positivity1013 (77.3%)630 (77.1%)383 (77.7%).809342 (80.1%)671 (76.0%).096
Medication use (ever):
TNF-a inhibitors588 (32.2%)447 (40%)141 (19.9%)<.0001nanana
MTX1119nanana447 (76.1%)672 (54.2%)<.0001
HCQ684 (37.4%)381 (34.1%)303 (42.7%).0002230 (39.1%)454 (36.6%).300
Corticosteroids1547 (84.6%)1006 (89.9%)541 (76.2%)<.0001546 (92.9%)1001 (80.1%)<.0001
NSAIDs1302 (71.2%)807 (72.1%)495 (69.7%).270445 (75.7%)857 (69.1%).004
Statins544 (29.7%)332 (29.7%)212 (29.9%).931169 (28.8%)375 (30.2%).519
Hypertension847 (46.3%)521 (46.6%)326 (45.9%).788262 (44.6%)585 (47.1%).301
Hyperlipidemia397 (21.7%)240 (21.5%)157 (22.1%).737117 (19.9%)280 (22.5%).197
Diabetes435 (23.8%)252 (22.5%)183 (25.8%).111115 (19.6%)320 (25.8%).004
Median (IQR)
Age at RA diagnosis58 (47–69)56 (46–67)61.5 (50–72)<.000152 (43–60)61 (51–71)<.0001
BMI29.2 (25.3–34.1)29.5 (25.6–34.9)28.7 (24.6–32.7).001230.2 (26.0–35.8)28.7 (25.0–32.9)<.0001
Sedimentation rate (max)33 (18–55)34 (20–55)31 (15–60).06535 (21–62)32 (17–53).004
LDL101 (80, 123)101 (81–122)126 (120, 132).946102 (80.8, 122.0)100 (79, 124).833
Systolic BP72 (69, 78)72 (70–78)72 (68–78).14172 (70, 79.5)71 (68, 78)<.001
Diastolic BP126 (120, 133)126 (120, 132)126.5 (120, 135).083124 (119, 132)126 (120, 134).020
* Ever Methotrexate or TNF usage prior to CAD diagnosis or censor date.
** P-values obtained either from Chi-square tests (frequencies) or Wilcoxon's test (medians).

Figure 1.

Figure 2.

To cite this abstract, please use the following information:
Bozaite-Gluosniene, Rasa, Tang, Xiaoqin, Kirchner, H. Lester, Antohe, Jana L., Morris, Stephanie J., Wasko, Mary Chester, et al; Reduced Cardiovascular Risk with Use of Methotrexate and Tumor Necrosis Factor- Inhibitors in Patients with Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :719
DOI:

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