Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: The systemic inflammation of rheumatoid arthritis (RA) can have detrimental effects on the hematopoietic and cardiovascular systems. Additionally, effective DMARD treatments for RA can be hemato- or hepatotoxic. The effects of adalimumab (ADA) in combination with methotrexate (MTX) therapy on these systems in patients with early or long-standing RA have not been previously summarized. This analysis evaluates the effects of ADA+MTX therapy compared to MTX monotherapy on laboratory and vital sign parameters relevant to hematopoietic, cardiovascular, and hepatic organ systems.
Methods: Clinical trials DE013 and OPTIMA (MTX-naïve patients, early RA, mean duration=0.8 yrs in DE013, 0.35 yrs in OPTIMA) and DE019 (MTX-incomplete responders, long-standing RA, mean duration=11 yrs) were double-blind studies that compared ADA+MTX therapy to MTX monotherapy for ≥6 months. This post hocanalysis determined the percentage of patients who developed neutropenia, lymphocytopenia, thrombocytopenia, anemia, reduction in Hgb from baseline, increases in creatinine, increases in AST or ALT, and prevalence of stage 2 hypertension at any time during the first 6 months of ADA treatment. Mean laboratory values and vital signs (all studies) and fasting lipids (OPTIMA only) were determined at baseline and 6 months and compared using a contrast within a one-way analysis of variance.
Results: Incidence rates for laboratory abnormalities are listed in the table. After 6 months, mean increase in Hgb levels was higher in ADA+MTX arms than in the MTX-only arms in early RA and in long-standing RA. Mean HDL cholesterol changes were not different in the ADA+MTX treatment group compared to MTX alone. Mean total and LDL cholesterol increased numerically with ADA+MTX therapy vs. MTX alone. No differences were observed in the incidences or mean changes in serum creatinine, ALT, or AST between ADA+MTX therapy and MTX alone.
Conclusion: Over an observation period of 6 months, RA patients treated with ADA+MTX exhibited laboratory abnormalities and hypertension at levels and frequencies similar to those seen in patients treated with MTX alone. In fact, ADA+MTX therapy was associated with a statistically significantly reduced incidence of anemia and lymphocytopenia. Similar results were observed whether evaluating ADA treatment in MTX-naïve patients or in those with long-standing RA.
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Table. Incidence and mean change from baseline in laboratory values of interest at 6 months of treatment |
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Early RA |
Long-standing RA |
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PBO+MTX N = 774 |
ADA+MTX N = 783 |
PBO+MTX N = 200 |
ADA+MTX N = 207 |
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Incidence, n (%) |
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Neutropenia |
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<1500 to 500/mm3 |
14 (1.8) |
25 (3.2) |
0 |
1 (0.5) |
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<500/mm3 |
1 (0.1) |
1 (0.1) |
0 |
0 |
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Lymphocytopeniaa |
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<800 to 500/mm3 |
56 (7.2) |
25 (3.2)* |
37 (18.5) |
17 (8.2)* |
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<500 to 200/mm3 |
15 (1.9) |
3 (0.4)* |
4 (2.0) |
2 (1.0) |
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Thrombocytopeniaa |
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50,000 to <75,000/mm3 |
0 |
1 (0.1) |
0 |
0 |
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Anemia |
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Hgb <10.0–8.0 g/dL |
55 (7.1) |
28 (3.6)* |
11 (5.5) |
3 (1.4)* |
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Hgb <8.0–6.5 g/dL |
4 (0.5) |
2 (0.3) |
0 |
0 |
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Hemoglobin decreased |
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Hgb decrease -3.0 to -1.0 g/dL |
263 (34.0) |
176 (22.5)* |
71 (35.5) |
45 (21.7)* |
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Hgb decrease >-3.0 g/dL |
3 (0.4) |
0 |
1 (0.5) |
2 (1.0) |
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Serum creatinine increased |
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>1.5 to 3X ULN |
5 (0.6) |
1 (0.1) |
0 |
0 |
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>3 to 6X ULN |
0 |
1 (0.1) |
0 |
0 |
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>6X ULN |
0 |
0 |
1 (0.5) |
1 (0.5) |
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AST increased |
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AST >3–5X ULN |
8 (1.0) |
10 (1.3) |
1 (0.5) |
1 (0.5) |
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AST >5X ULN |
2 (0.3) |
1(0.1) |
2 (1.0) |
0 |
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ALT increased |
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ALT >3–5X ULN |
17 (2.2) |
23 2.9) |
1 (0.5) |
2 (1.0) |
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ALT >5X ULN |
3(0.4) |
5 (0.6) |
2 (1.0) |
0 |
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Stage 2 hypertensionb |
79 (10.2) |
82 (10.5) |
52 (26.0) |
64 (30.9) |
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Mean change from baseline |
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Hemoglobin, g/dL |
0.24 |
0.45* |
0.18 |
0.44* |
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Fasting lipidsc |
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HDL cholesterol, mmol/L |
0.078 |
0.119 |
– |
– |
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LDL cholesterol, mmol/L |
0.193 |
0.284* |
– |
– |
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Cholesterol, mmol/L |
0.280 |
0.438* |
– |
– |
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*P <.05 for ADA+MTX vs. PBO+MTX; χ 2 test for incidence rates. an=0 for low values/categories not shown; bsystolic BP≥160 mm Hg or diastolic BP≥100 mm Hg; cOPTIMA study only. /mm3, cells per cubic millimeter; ADA, adalimumab; AST, aspartate transaminase; ALT, alanine transaminase; g/dL, gram per deciliter; HDL, high-density lipoprotein; Hgb, hemoglobin; LDL, low-density lipoprotein; MTX, methotrexate; PBO, placebo; RA, rheumatoid arthritis; ULN, upper limit of normal. |
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Disclosure:
D. Furst,
Abbott, Actelion, Amgen, BiogenIdec, BMS, Centocor, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, and UCB,
2,
Abbott, Actelion, Amgen, BiogenIdec, BMS, Centocor, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, and UCB,
5,
Abbott, Actelion, Amgen, BiogenIdec, BMS, Centocor, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, and UCB,
8;
A. P. Lacerda,
Abbott Laboratories,
3,
Abbott Laboratories,
1;
N. Andhivarothai,
Abbott Laboratories,
3,
Abbott Laboratories,
1;
J. Kalabic,
Abbott Laboratories,
3,
Abbott Laboratories,
1;
N. Mozaffarian,
Abbott Laboratories,
1,
Abbott Laboratories,
3.
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