Cost optimizing tocilizumab therapy in stable rheumatoid arthritis: a dose de-escalation nomogram to prevent overuse...

The conventional 8 mg/kg tocilizumab (TCZ) dose regimen for rheumatoid arthritis (RA) yields higher serum trough concentrations (TCZ_trough) than needed (> 1 mg/L) for C-reactive protein normalization and disease control. We evaluated the registered dosing approach by TCZ_trough assessment using pharmacokinetic (PK) modelling and introduced a practical TCZ_trough-guided dose reduction nomogram.

This prospective cohort study examined RA patients with stable disease activity undergoing intravenous TCZ treatment. A population PK model was constructed utilizing literature PK-data, TCZ_trough, and dosing information. The derived model enabled prediction of TCZ_trough guided dose de-escalation constructed in a nomogram. Dose reduction was implemented in a study subgroup, involving a reassessment of TCZ_trough and maintenance of disease activity control.

In 39 patients treated according to the registered dose-scheme, the baseline mean TCZ_trough was 27.6 mg/L (SD 12.6). Simulations using the constructed PK-model demonstrated that a 0.4-4.6 mg/kg dose reduction was feasible in 36 patients (92%). The simulated reduction corresponds with an annual cost-reduction of approximately 25% per patient. Twelve consecutive patients were selected for the prospective validation of a model-based dose reduction nomogram. In all patients TCZ_trough remained above 1 mg/L upon reduction, while the median TCZ_trough decreased by 25 mg/L. After 18 months, 75% (n = 9) of these patients continued to receive reduced TCZ dosages, while maintaining stable disease.

TCZ_trough guided dose de-escalation based on a proposed nomogram results in considerable cost reductions, while efficacy is maintained in most patients. Through routine monitoring of TCZ_trough in stable RA patients, dose reduction can be implemented, potentially leading to optimization of cost-effective TCZ therapy. Key Points • Tocilizumab (TCZ) levels at a registered dosage (8 mg/kg) substantially exceed the minimally required concentration for disease control. • Although the pharmacokinetics of TCZ are well established, TCZ trough levels (TCZtrough) are rarely used to guide individualized dose reduction strategies in routine RA practice. • When reducing TCZ use, dose reduction is preferred above extending the dose interval for achieving sufficient TCZtrough. • Dose de-escalation based on TCZtrough measurement and a nomogram leads to a substantial dose reduction while maintaining efficacy, potentially reducing TCZ costs by 25%.