Therapeutic Drug Monitoring of Tocilizumab in Rheumatoid Arthritis

• Status: Unknown status
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tel-Aviv Sourasky Medical Center
• Collaborator: Amsterdam Rheumatology and Immunology Center

Criteria

Inclusion Criteria:

• RA according to the ACR 1987 or 2010 criteria;

• Current use of tocilizumab IV, with a consistent interval of 4 weeks for at least 24 weeks.

• 18 years of age and older.

Exclusion Criteria:

• A potential subject will be excluded from participation in case of a scheduled surgery in the next 20 weeks or other preplanned reasons for treatment discontinuation.

• Children, pregnant women and individuals with a lack of judgement.