Research into administration of lower dosed rituximab using an injection in patients with Rheumatoid Arthritis

Rituximab (RTX) is a chimeric antibody directed at CD20 positive B-cells that is authorized for the treatment of rheumatoid arthritis (RA) in the dosage of 2x 1000 mg every six months. A large systematic review showed that low-dose RTX (1x 1000 mg or 2x 500 mg) is as efficacious for RA as this higher dose. Recently, the REDO-study has been performed, demonstrating a good response on continued treatment with even ultra-low dose RTX (1x 500 or 1x 200 mg) for a large proportion of RA patients. After dose optimization, patient friendliness and organization of care might be further improved when rituximab can be administered subcutaneously. Therefore, we want to explore the therapeutic possibilities of subcutaneous (SC) administration of ultra-low dose RTX, by performing a pharmacokinetic non-inferiority study using the already authorized subcutaneous formulation of Roche (MabThera 1400 mg solution for subcutaneous injection (120 mg/ml:11.7 ml), registered for non-Hodgkin lymphoma. Patients with RA, using RTX IV 500 or 200 mg every 6 months, with stable disease activity will be included. Previous non-response to ultra-low dose RTX or a contraindication or objection to receive either therapy are reasons for exclusion. Patients will be randomized between RTX 336 mg subcutaneous or 200 mg intravenous. Blood samples for rituximab serum levels, anti-drug antibodies and CD20+ B-cells will be drawn pre-dose, post-dose (after infusion for the IV group, 2-4 days after injection for the SC group), after 3 months and after 6 months. Disease activity using DAS28-CRP will be measured at baseline, after 3 months and after 6 months. The main endpoint of the study is pharmacokinetic non-inferiority based on AUC0-6months between RTX 200 mg intravenous and 336 mg subcutaneous.

We expect to find pharmacokinetic non-inferiority between RTX 336 mg subcutaneous and 200 mg IV

Baseline; 3 days (SC only); 3 months; 6 months

Rituximab 336 mg subcutaneous (MabThera 1400 mg solution for subcutaneous injection (120 mg/ml:11.7 ml); Rituximab 200 mg intravenous (Rixathon 100 mg concentrate for solution for infusion)