Background Tocilizumab (TCZ) is a humanized monoclonal antibody against interleukin-6 receptor used to treat active rheumatoid arthritis (RA). The response to treatment may depend on the serum levels achieved, which depend on the interval and the total dose administered.
Objectives To analyze serum levels of TCZ and antidrug antibodies (ADA) in RA patients on chronic treatment with TCZ and evaluate their relationship with disease activity, serum levels of IL6 and CRP and drug dosage.
Methods Cross-sectional study including all RA patients on chronic treatment with TCZ attended by our Arthritis Unit. Demographic data, disease activity, IL6, CRP, and TCZ (adequate = ≥5 ug/ml) serum levels and ADA (LISA TRACKER Tocilizumab LTT005 DuoDrug + ADAb) were collected. The dose and dose interval were correlated with clinical and serological parameters.
Results 33 RA patients were included (91% female, 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 had ADA. Serum TCZ levels were suboptimal (<5 ug/ml) in 20 patients (60%), of whom 10 had non-detectable levels (<1 ug/ml). Patients with adequate levels of TCZ had higher levels of IL6 and lower DAS28 and CRP than those with suboptimal levels (Table 1). 15 patients received a reduced dose of TCZ (4-6 mg/kg) due to persistent remission or low disease activity and these patients had serum levels of TCZ lower than patients on the standard dose, with no between-group differences in disease activity or CRP (Table 2). IL6 levels and TCZ serum levels were positively correlated (R2=0.268, p=0.005), but not DAS28 or CRP. In 3 patients, all with low disease activity, a curve of TCZ serum levels was made 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 throughout.
Conclusions No ADA were found in RA patients treated with TCZ. Adequate levels of TCZ were associated with higher IL6 levels, lower DAS28 and, especially, lower CRP levels. More than 50% of patients had suboptimal or non-detectable drug levels, particularly those receiving a reduced TCZ dose, but most had achieved low disease activity or remission.
Disclosure of Interest None declared