Therapeutic Drug Monitoring of Tocilizumab in Rheumatoid Arthritis
Status:
Unknown status
Trial end date:
2019-12-01
Target enrollment:
Participant gender:
Summary
Rationale: A wide range of serum trough concentrations is observed in tocilizumab-treated
rheumatoid arthritis (RA) patients, while 1 mg/L tocilizumab is sufficient to block systemic
interleukin-6 receptor. A substantial proportion of patients has higher serum tocilizumab
concentrations and is likely to be overexposed. We expect that patients can at least reduce
the dose aiming for a concentration of 5 mg/L without reducing efficacy.
Objective: To evaluate the feasibility of the study after 20 weeks of follow-up, this
includes the evaluation of the dose-reduction algorithm in tocilizumab-treated patients with
RA.
Study design: Double-blind randomized controlled pilot study with a follow up of 20 weeks.
Study population: Consecutive RA patients that are treated with tocilizumab intravenously
every four weeks for at least 24 weeks. Patients are screened for tocilizumab concentration
after signing informed consent.
Intervention: Patients with a concentration below 5 mg/L will continue the dose. Those
patients with a tocilizumab concentration above 5 mg/L are randomly assigned (2:1) to dose
reduction or to continuation of the standard care tocilizumab dose. In the intervention
group, the precise dose-reduction is calculated per patient in order to achieve a tocilizumab
concentration of 5 mg/L (range 4-6 mg/L).
Main study parameters/endpoints:
The feasibility of the study logistics is evaluated according to the dropout rate and
patients opinion about the study. Second, the proportion of patients achieving the targeted
tocilizumab concentration after dose reduction is evaluated.
Nature and extent of the burden and risks associated with participation, benefit and group
relatedness:
Dose-reduction will lead to lower drug costs and possibly to reduce the risk of adverse
events. Since we lower the tocilizumab concentration in a proportion of the patients, risk of
a exacerbation of the disease exists. In this case, patients will receive their original
dose. Previous studies showed that disease activity is controlled adequately after returning
to the standard dose. However, our algorithm is designed to reach concentrations of 5 mg/L
(range 4-6 mg/L) and studies showed that 1 mg/L of tocilizumab is sufficient to maintain
clinical effect. The expected burden of this study is low, since study visits are planned at
the time of infusion and therefore do not take extra time. The additional burden consists of
an extra blood sample taken every visit and the fingerprick that is performed once.