Background/Purpose

Tocilizumab (TCZ) is a humanized monoclonal antibody against interleukin-6 receptor used for the treatment of active rheumatoid arthritis (RA). The response to this treatment may depend on the serum levels achieved, which depends on the interval and the total dose administered.

Purpose

To analyze TCZ serum trough levels and antidrug antibodies (ADA) in a cohort of RA patients in chronic treatment with TCZ; and to evaluate its relationship with disease activity, serum levels of IL6 and CRP and drug levels.

Methods

Cross-section study including all RA patients attended in our Arthritis Unit undergoing chronic treatment with TCZ. Analysis of demographic data, disease activity IL6 and CRP serum levels together with TCZ serum levels and ADA (LISA TRACKER Tocilizumab LTT005 DuoDrug + ADAb) was done. All drug levels were measured before treatment infusion. Drug levels were correlated with different clinical and serological parameters.

Results

33 RA patients were included (91% women, age 53 ±12 years, disease duration 15.3 ± 9.7 years, anti-CCP+ 66.7%, monotherapy 22.2%, DAS28 2.9 ± 1.1). No patient showed presence of ADA. In 14 patients (42%) serum levels of TCZ were non-detectable (<1 ug/ml). Patients with detectable levels of TCZ showed higher levels of IL6 and lower levels of CRP than those with non-detectable levels (Table). 15 patients received reduced dose of TCZ (4-6 mg/Kg) due to persistent remission or low disease activity. In these patients serum levels of TCZ were lower than in those with standard dose, without differences on disease activity or CRP between groups. A significant positive correlation was found between IL6 levels and TCZ serum levels (R2=0.268, p=0.005), but not with DAS28 or CRP. In 3 patients, all of them with low disease activity, a curve of TCZ serum levels was done by TCZ dosage at baseline (before drug infusion) and 10, 20 and 28 days thereafter. In two patients, TCZ serum levels were not detectable by day 20. The third patient showed adequate levels through the entire period.

Conclusion

In a clinical setting of RA patients in treatment with TCZ no ADA were found.  An important proportion of RA patients treated with TCZ had undetectable serum trough levels (42%), showing higher CRP levels, and lower IL-6, but no differences were found in disease activity measured by DAS28-ESR.

Distribution of patients according to TCZ serum trough levels

	Non detectable drug levels (< 1 ug/ml) n=14	Detectable drug levels (> 1 ug/ml) n=19	p
Dose interval (days – mean)	31.9 ± 3	29.9 ± 3	0.323
Serum IL6 levels (ug/ml)	2.8 ± 2.3	7.8 ± 2	0.012
CRP (mg/dl)	1.1 ± 1.4	0.1 ± 0.3	0.001
Hemoglobin (g/dl)	13.5 ± 15	12.8 ± 12	0.214
Reduced dose of TCZ (%)	79%	42%	0.053
DAS28-ESR	3.1 ± 1	2.8 ± 1	0.499
Remission (DAS28-ESR<2.6) (%)	29%	37%	0.956

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tocilizumab-serum-trough-levels-and-its-relationship-with-disease-activity-and-drug-dosage-in-rheumatoid-arthritis-patients/