Therapeutic Drug Monitoring of Tocilizumab in Rheumatoid Arthritis

Sponsor
Tel-Aviv Sourasky Medical Center
Study ID
NCT03781310
Phase
PHASE4
Status
Unknown

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Tocilizumab — DRUG
    IV Tocilizumab once every 4 weeks at reduced dose according to algorithm.

Study Details

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.

Key Dates

Start date
Dec 31, 2018
Status verified
Dec 2018
Primary completion
Jun 30, 2019
Completion
Dec 31, 2019

Study Design

Enrollment
80 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Dose reduction
    Reduce the Tocilizumab dose at the baseline visit (week 0) and maintain that dose until 20 weeks of follow-up. The reduced dose is dependent of the tocilizumab serum concentration, measured at the screening visit, and is calculated according to the pre-defined dose-reduction algorithm.
  • Active Comparator: Maintain dose
    Maintain the original dose at baseline visit (week 0) until 20 weeks of follow-up.

Primary Outcome Measure

Disease flare rate [ Time Frame: 20 weeks ]

Central Contacts

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