Tapering of Rituximab Based on Interval Prolongation Compared to Disease Activity-guided Dose Reduction in Patients With Rheumatoid Arthritis

Comparison of disease activity in both study arms, measured using the Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP)

Main secondary outcome. DAS28-CRP range: 0 - ..., with higher values indicating higher disease activity.

Time frame: Over 2 years (104 weeks)

Comparison of disease activity in both study arms, measured using the Simplified Disease Activity Index (SDAI)

SDAI range: 0 - ..., with higher values indicating higher disease activity.

Time frame: Over 2 years (104 weeks)

Comparison of cumulative dose of rituximab in both study arms

Time frame: Over 2 years (104 weeks)

Comparison of cumulative dose of glucocorticoids in both study arms

Time frame: Over 2 years (104 weeks)

Proportion of patients in both study arms achieving a good or moderate European League Against Rheumatism (EULAR) treatment response after administration of rituximab, over a period of 2 years (104 weeks)

A good EULAR response is defined as a decrease in Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) \> 1.2 and a present DAS-CRP ≤ 3.2. A moderate EULAR response is defined as a decrease in DAS28-CRP \> 0.6 to ≤ 1.2 and a present DAS28-CRP ≤ 5.1, or a decrease in DAS28-CRP \> 1.2 and a present DAS28-CRP \> 3.2. Treatment responses will be evaluated 12 weeks after every administration of rituximab.

Time frame: Over 2 years (104 weeks)

Comparison of loss of disease control in both study arms

Loss of disease control is defined as achieving a Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) \> 3.2 with previous DAS28-CRP ≤ 3.2.

Time frame: Over 2 years (104 weeks)

Comparison of rituximab drug retention rate in both study arms

Defined as the percentage of patients remaining on treatment with rituximab over time.

Time frame: Over 2 years (104 weeks)

Proportion of patients tapering rituximab below 1000 mg in the experimental arm

Time frame: Over 2 years (104 weeks)

Mean/median interval between rituximab administrations in the active comparator group

Time frame: Over 2 years (104 weeks)

Comparison of serious adverse events/reactions rates in both study arms.

An adverse event or adverse reaction is considered serious if it leads to inpatient hospitalization or prolongation of existing hospitalization, if it results in persistent or significant disability or incapacity, if it results in a life-threatening experience (meaning that the subject was at risk of death), or if it results in death.

Time frame: Over 2 years (104 weeks)

Comparison of serious infections rate in both study arms.

An infection is considered serious if it leads to inpatient hospitalization or prolongation of existing hospitalization, if it results in persistent or significant disability or incapacity, if it results in a life-threatening experience (meaning that the subject was at risk of death), or if it results in death.

Time frame: Over 2 years (104 weeks)