Abstract Number: 59/O131RItuximab long-term DOSE trial in Multiple Sclerosis RItuximab long-term DOSE trial in Multiple Sclerosis – RIDOSE-MS. A phase 3 trial investigating extended RIDOSE-MS. A phase 3 trial investigating extended dosing regimen of rituximab in relapsing-remitting MS dosing regimen of rituximab in relapsing-remitting MS Anders Svenningsson
Introduction: In the RIFUND-MS trial (NCT02746744), we demonstrated a superior effect of rituximab (RTX) compared with dimethyl fumarate (DMF) for prevention of relapses and focal MRI activity in relapsing-remitting multiple sclerosis (RRMS). However, the optimal dosing regimen of RTX for optimization of the benefit-to-risk balance is not known. Objectives/Aims: To compare the efficacy and safety of an extended 12-month dosing regimen with a standard dosing with RTX. Every 6 months. Methods: The RIDOSE-MS trial was a rater-blinded randomized phase 3 trial comparing 500 mg RTX given 12-monthly with 500 mg 6-monthly over a 3-year period after an initial common 1-year with 6-monthly dosing. The primary outcome was non-inferiority of the extended dosing regimen regarding no evidence of disease activity (NEDA)-3: no relapses, no new or enlarging T2 MRI lesions and no confirmed disability worsening, over the 3year randomized period. Secondary outcomes involved levels of biomarkers and immunological side effects, particularly decrease in immunoglobulin G (IgG) levels and development of hypogammaglobulinemia.
Results: So far, data on relapses and MRI activity have been analyzed. A total of 207 individuals were randomized to each treatment arm, 104 to the 12-monthly and 103 to the 6-monthly arm. There were in total reported 12 protocol-defined relapses over the entire trial period of 4 years yielding an annual relapse rate of 0.015 for both arms combined. This is the same relapse rate as in the RTX arm of the previous RIFUND-MS trial, comparing RTX with DMF. Seven of these relapses occurred in the 6-monthly arm and five in the 12-monthlyarm (p=0.5). In total 36 new lesions appeared in 22 unique patients (12 in the 12-monthly and 10 in the 6monthly arm) during the whole trial period (p=0.7). Adverse events were equally distributed between the treatment arms. The reduction rate of IgG was approximately 25% slower in the 12-monthly compared with the 6-monthly group. Conclusion: The RIDOSE-MS trial shows that yearly treatment of 500 mg rituximab is highly effective and non-inferior to 6monthly treatment for the inflammatory manifestations of MS. Although we did not see any signal of less infections in the extended dose arm, the lower decline on immunoglobulin levels might lead to long-term safety benefits from a lower accumulated dose over time.
Source: multiple-sclerosis-research.org