Dose reduction of rituximab in clinical practice: a retrospective cohort study of rheumatoid arthritis patients in low disease activity on rituximab.

Abstract

To determine the effects of dose reduction of rituximab (RTX) on rheumatoid arthritis (RA) disease activity in clinical practice. Retrospective cohort study of RA patients using RTX, in stable low disease activity (i.e. Disease Activity Score 28-joint count CRP (DAS28-CRP) ≤3.5 for ≥6 consecutive months) and ≥2 DAS28-CRP measurements. We identified three treatment periods: 1) full dose RTX, 2) RTX dose reduction, and 3) stable RTX dose (and interval) after tapering. Linear mixed-model analysis was used to estimate mean DAS28-CRP during these periods. Rituximab use was assessed as the median percentage of the RTX Daily Defined Dose (%DDD) per period, with 1 x 1000 mg/6 months as reference. 387 patients were included in the cohort with a median of 8 DAS28-CRP measurements (Q1-Q3:4-13) available per patient and median follow-up time of 44 months (Q1-Q3: 23-76). 299 patients tapered RTX and entered period 2 at least once, of whom 226 also entered period 3. Mean DAS28-CRP were 2.37 (95% CI: 2.29, 2.44) for period 1, 2.33 (95% CI: 2.25, 2.40) for period 2, and 2.27 (95% CI: 2.18, 2.35) for period 3, the latter significantly lower compared to period 1 (p=0.025). %DDD for the three time periods were 96%, 57% and 49%, respectively. Dose reduction of RTX in clinical practice is effective for many RA patients and leads to relevant dose reduction. Together with other previously proven benefits of ultra-low dose RTX, wider implementation of ultra-low dose RTX in RA patients should be considered.