Use of Tocilizumab Drug Levels to Optimize Treatment in RA

Summary

Tocilizumab concentrations above 1 mg/L are likely to be sufficient for normalizing C-reactive protein (CRP) production in patients with rheumatoid arthritis (RA). In practice, however, a large variability in the concentrations of tocilizumab is found, and a large proportion of patients treated with tocilizumab subcutaneously (sc) have concentrations far above 1 mg/L. These patients can probably lower their doses without losing clinical response. A 52 weeks non-inferiority, multicenter, randomized controlled study will be performed to investigate whether patients with RA with serum trough concentrations of tocilizumab higher than 15 mg/L can increase their dosing interval to every two weeks without losing clinical response. Patients with relatively high trough concentrations will be randomly assigned to continuation of the standard dose or to increase dosing interval to every two weeks. The main objective is to investigate the difference in mean time weighted Disease Activity Score in 28 joints, including erythrocyte sedimentation rate (DAS28-ESR) between the two groups after 28 weeks. It is expected that patients with relatively high trough concentrations can safely increase their dosing interval without losing response.

Timeline

Start

2020-03-01

Primary completion

2024-12

Completion

2024-12

Publications

• Background Kneepkens EL, van den Oever I, Plasencia CH, Pascual-Salcedo D, de Vries A, Hart M, Nurmohamed MT, Balsa A, Rispens T, Wolbink G. Serum tocilizumab trough concentration can be used to monitor systemic IL-6 receptor blockade in patients with rheumatoid arthritis: a prospective observational cohort study. Scand J Rheumatol. 2017 Mar;46(2):87-94. doi: 10.1080/03009742.2016.1183039. Epub 2016 Jul 20.
• Background l'Ami MJ, Krieckaert CL, Nurmohamed MT, van Vollenhoven RF, Rispens T, Boers M, Wolbink GJ. Successful reduction of overexposure in patients with rheumatoid arthritis with high serum adalimumab concentrations: an open-label, non-inferiority, randomised clinical trial. Ann Rheum Dis. 2018 Apr;77(4):484-487. doi: 10.1136/annrheumdis-2017-211781. Epub 2017 Sep 22.
• Background Frey N, Grange S, Woodworth T. Population pharmacokinetic analysis of tocilizumab in patients with rheumatoid arthritis. J Clin Pharmacol. 2010 Jul;50(7):754-66. doi: 10.1177/0091270009350623. Epub 2010 Jan 23.
• Background Bastida C, Ruiz-Esquide V, Pascal M, de Vries Schultink AHM, Yague J, Sanmarti R, Huitema ADR, Soy D. Fixed dosing of intravenous tocilizumab in rheumatoid arthritis. Results from a population pharmacokinetic analysis. Br J Clin Pharmacol. 2018 Apr;84(4):716-725. doi: 10.1111/bcp.13500. Epub 2018 Feb 7.

Drugs

Indications