Session Information
Date: Sunday, November 8, 2015
Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
Tocilizumab (TCZ) is a humanized anti-IL-6R monoclonal antibody approved for the treatment of active rheumatoid arthritis (RA) (EMA: 8mg/kg q4w). Response to treatment may depend on the dose as well as on the achieved seric levels.
Purpose
To analyze the serum levels of TCZ in two cohorts of RA patients on chronic treatment with IV TCZ and its relationship with disease activity and disease remission. To establish a cut-off point of TCZ serum levels with high discriminative capacity for disease remission.
Methods:
Cross-sectional study of 2 cohorts (Barcelona, Spain and Lausanne, Switzerland) that included all RA patients on chronic treatment with IVTCZ. Demographic, disease activity, serum markers, TCZ trough levels (detectable levels > 1 μg/ml) (LISA TRACKER Tocilizumab Theradiaag, France) and IL6 levels (ELISA) were analyzed. Samples were collected just before treatment infusion. TCZ levels were correlated with different clinical and serological parameters. Multivariate logistic regression was calculated to determine variables associated with remission (DAS28 ≤2.6). ROC curve analysis was performed to study the discriminatory capacity of the area under the curve (AUC) of TCZ levels associated with remission.
Results:
77 RA patients were included (40 Barcelona Cohort, 37 Lausanne Cohort). 89.6% were women, with a mean age of 55.17 ± 13.4 years and a disease duration of 13.8 ± 8.4 years; 70.1% were FR and/or anti-CCP positive. 42.9% of patients were on monotherapy, 40.3% were receiving low dose glucocorticoids and 22.1% were on reduced dose of TCZ (6 or 4 mg/kg q4w). 43 patients (56.6%) were on remission. Swiss patients had lower disease activity and were more frequently on remission, and used corticosteroids and DMARD combination therapy less frequently. 20 patients (26%) had undetectable levels of TCZ (<1 μg/ml). This situation was associated with significantly higher levels of CRP, lower levels of IL-6 and higher DAS28; but there were no differences in tender and swollen joint count (Table). Patients in remission had higher levels of TCZ and had more frequently detectable levels of TCZ in comparison with those patients that were not in remission. The cut-off point of 3.48 μg/ml had the greatest discriminative capacity for clinical remission (AUC 0.724; 95% CI: 0.607-0.840; p=0.001) with a sensitivity of 79.5% and a specificity of 67%. In the multivariate analysis the presence of levels ≥ 3.48 μg/ml of TCZ and the use of corticosteroids were independently associated with clinical remission.
Conclusion: Detectable levels of TCZ (≥1 μg/ml) in RA patients in chronic treatment with TCZ were associated with a lower CRP values. The cut-off point of serum TCZ with best discriminative capacity for clinical remission was 3.48 μg/ml. Serum levels of TCZ ≥ 3.48 μg/ml may be more adequate to achieve clinical remission or low disease activity.
Table. Patients with detectable and undetectable serum levels of TCZ.
|
|
Undetectable Serum trough levels <1μg/ml (n=20) |
Detectable Serum trough levels ≥1μg/ml (n=57 ) |
p |
|
Reduced dose, n (%) |
9 (45) |
8 (14) |
0.010 |
|
FR and/or anti-CCP+, n (%) |
18 (85) |
37 (64.9) |
0.154 |
|
IL-6 serum levels, mean ±SD (pg/ml) |
2.8 ± 2.3 |
7.4 ± 0.9 |
<0.001 |
|
CRP, mean ± SD (mg/dl) |
1.02 ± 1.3 |
0.1 ± 0.2 |
0.007 |
|
ESR, mean ± SD (mm/h) |
17.1 ± 26.6 |
7 ± 6.1 |
0.107 |
|
TJC, mean ± SD |
2.45 ± 2.8 |
1.86 ± 3.1 |
0.452 |
|
SJC, mean ± SD |
2.15 ± 3.3 |
2.09 ± 2.4 |
0.930 |
|
DAS 28-ESR, mean ± SD |
3.04 ± 1.2 |
2.24 ± 1 |
0.005 |
|
Remission DAS 28-ESR ≤ 2.6, n (%) |
6 (30) |
37 (64.9) |
0.008 |
|
Low Disease Activity DAS28-ESR ≤ 3.2, n (%) |
13 (65) |
48 884.2) |
0.057 |
|
CDAI mean ± SD |
11.69 ± 7.7 |
10.58 ± 5.9 |
0.611 |
|
Corticosteroids, n (%) |
8 (40) |
23 (40.4) |
1.000 |
|
Monotherapy, n (%) |
8 (40) |
25 (43.8) |
0.799 |
To cite this abstract in AMA style:
Ruiz-Esquide V, Zufferey P, Inciarte-Mundo J, Yagüe J, Hernández MV, Ramirez J, Berner J, Pascal M, Cuervo A, Cañete JD, Sanmarti R. Tocilizumab Serum Trough Levels and Disease Activity in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/tocilizumab-serum-trough-levels-and-disease-activity-in-rheumatoid-arthritis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/tocilizumab-serum-trough-levels-and-disease-activity-in-rheumatoid-arthritis/