Background/objectives The approved dose of RTX in RA is 1000 mg x2, but some data have suggested similar clinical efficacy with 500 mg x2. The purpose of this analysis was to compare the efficacy of the two dosages given as first or second treatment course.

Methods Ten European registries submitted anonymised datasets with demographic, efficacy and treatment data for patients who had started RTX. Efficacy of treatment and retreatment was assessed based on DAS28 reductions and EULAR responses after 6 months.

Results Data on RTX dose were available for 2873 out of 3266 patients in CERERRA. 2625 (91.4%) and 248 (8.6%) patients received 1000mg x2 and 500mg x2, respectively. Patients who were treated with the lower dose (LD) were significantly older (mean±SD: 55.2±15.8 vs 52.6±12.6, years, p=0.002), had longer disease duration (13.6±11.9 vs 10.9±8.2, years, p<0.0001), higher number of prior DMARDs (2.6±1.3 vs 2.4±1.4, p=0.04) but lower number of prior biologics (0.7±0.9 vs 1.0±1.0, p<0.0001) and lower baseline DAS28 (5.7±1.3 vs 5.9±1.3, p=0.02) than those treated with the higher dose (HD). Additionally they were less likely to receive concomitant DMARDs (72.6% vs 83.1%, p<0.0001) but more likely to receive concomitant corticosteroids (65.7% vs 59.3%, p=0.03).

Both dosages lead to significant clinical outcomes at 6 months. Patients with the HD achieved numerically slightly greater DAS28 reductions at 6 months compared to those treated with the LD (mean DeltaDAS28±SD = 1.9±1.4 vs 1.7±1.4, p=0.5 corrected for baseline DAS28). Similar percentages of patients achieved EULAR good response (55.2% vs 50%, p=NS) and remission (10.5% vs 10.7%, p=NS) in the HD and LD groups, respectively.

At 6±1.5 months 579 patients received retreatment with HD RTX and 26 patients with LD. Patients who received a different dose at retreatment than at first treatment, as well as patients who were retreated at different time points during the first year, were disregarded from the analysis. Retreatment with HD led to even greater DAS28 reductions at 12 than at 6 months (DeltaDAS28 6 m=1.85±1.19, DeltaDAS28 12 m=2.52±1.47, p by paired t test <0.0001), while retreatment with LD led to no significant further DAS28 reduction (6 m=1.61±1.41, 12 m=1.27±1.78, p=0.2). A significantly higher good responders rate was observed for the HD of RTX in retreated patients (60.7% vs 32.1%, p=0.003).

Conclusion In this large observational cohort initial treatment with RTX at 500 mg x2 and 1000 mg x2 led to comparable clinical outcomes. The HD was associated with further DAS28 reductions when given as a second treatment course.