Concentration-guided dose reduction versus standard dosing in tocilizumab-treated rheumatoid arthritis patients: a randomised, international, multicenter, non-inferiority trial (TODORA)

Concentration-guided dose reduction versus standard dosing in tocilizumab-treated rheumatoid arthritis patients: a randomised, international, multicenter, non-inferiority trial (TODORA) - Use of tocilizumab drug levels to optimize treatment of RA (TODORA)

Status

Recruiting

Phases

Unknown

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON52409

Enrollment

Registered

2019-05-15

Start date

2020-04-16

Completion date

Unknown

Last updated

2025-08-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid arthritis

Interventions

All patients with a tocilizumab concentration above 15 mg/L will be randomised, and those patients that are allocated in the intervention group will reduce the dose by prolonging the dose-interval f

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: - Rheumatoid arthritis according to the ACR 1897 or 2010 criteria; - Current use of subcutaneous tocilizumab 162 mg weekly, for at least the last 6 months; - The treating rheumatologist is convinced of the benefit of tocilizumab continuation; - No changes in the treatment with glucocorticoids and DMARDs such as methotrexate in the past 3 months; - Written informed consent.

Exclusion criteria

Exclusion criteria: A scheduled surgery in the next 12 months or other pre-planned reasons for treatment discontinuation.

Design outcomes

Primary

Measure	Time frame
The primary objective of the study is to investigate the difference in mean time weighted Disease Activity Score in 28 joints (DAS28-ESR) after 28 weeks in patients with RA with serum trough concentrations higher than 15 mg/L who are randomly assigned to continuation of the standard dose or to increase dosing interval to every two weeks.	—

Secondary

Measure	Time frame
The secondary objectives of the study are to investigate the difference in mean time weighted DAS28-ESR after 52 weeks, and the difference in Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and HAQ score after 28 and 52 weeks, between the two treatment groups; to study the direct medical costs of using TDM to identify overexposure; to study the difference in number of flares between the two treatment arms at 28 and 52 weeks; to study the number and severity of adverse events in both treatment arms; to determine the difference in drug levels between the two treatment arms after 52 weeks; to study the relationship between dose, drug concentration, and clinical disease activity; to invent a pharmacokinetic model and develop an algorithm and a dashboard system to assure the implementation of TDM in clinical practice; and to study the perspective of patients towards concentration-guided dosing.	—

Measure

Time frame

The secondary objectives of the study are to investigate the difference in mean time weighted DAS28-ESR after 52 weeks, and the difference in Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and HAQ score after 28 and 52 weeks, between the two treatment groups; to study the direct medical costs of using TDM to identify overexposure; to study the difference in number of flares between the two treatment arms at 28 and 52 weeks; to study the number and severity of adverse events in both treatment arms; to determine the difference in drug levels between the two treatment arms after 52 weeks; to study the relationship between dose, drug concentration, and clinical disease activity; to invent a pharmacokinetic model and develop an algorithm and a dashboard system to assure the implementation of TDM in clinical practice; and to study the perspective of patients towards concentration-guided dosing.

—

Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)