Background The optimal long-term treatment regime for rituximab rheumatoid arthritis is unclear. In the first cycle, 2x1000mg is superior to 2x500mg. In repeat cycles, B cell numbers are often lower than baseline and 2x500mg has been reported to be similarly effective to 2x1000mg.  However, duration of response with dose reduction has not previously been investigated.
Objectives In responders to full dose of rituximab: to evaluate the level and duration of response to retreatment using reduced dose rituximab on relapse.
Methods Patients who had received at least one cycle of 2x1000mg rituximab with EULAR moderate or good response were treated with 2x500mg on clinical relapse (increase in DAS28>0.6) and comparison was made between 4-month DAS28 and duration of response (time to retreatment) between the last cycle of 2x1000mg and the first cycle of 2x500mg.
Results 137 patients were studied. Mean (SD) age at baseline was 63.6y (10.1), 78% were female, 67% received concomitant methotrexate, 29% received alternative concomitant DMARDs and 4% received no concomitant DMARD. Median (range) number of prior non-biologic and biologic DMARDs were 2 (0-7) and 1 (0-4) respectively. Patients had received median 5 (2-10) prior cycles of rituximab. Mean (SD) DAS28 4 months after the last 2x1000mg cycle and first 2x500mg cycle were 2.83 (1.09) and 3.08 (2.47) respectively (p=0.324). Median (IQR) time to retreatment after the 2x1000mg and 2x500mg cycles were 49.86 (40.14-65.71) and 39.14 (31.21-55.29) weeks respectively. (p<0.0001) Duration of response on 2x500mg rituximab was at least 1 month shorter than the previous 2x1000mg rituximab in 54% of patients, at least 3 months shorter in 37% of patients, and at least 6 months shorter in 15%. Following the 2x500mg cycle, 59 (43.1%) patients were switched back to 1000x2mg due to inferior overall clinical response.
Conclusions In line with previous reports, we did not see a significantly worsening of initial DAS28 response when patients who had responded to 2x1000mg rituximab switched to 2x500mg in retreatment. However, duration of response was significantly worse, with approximately 2-3 month reduction in time to retreatment. Due to increased frequency of retreatment, use of lower dose rituximab will entail greater infusion costs and use of concomitant glucocorticoids to control infusion reactions and flares. The cost effectiveness and safety of lower dose regimes may therefore not be as great as suggested by cost of drug and initial DAS28 response.
Mariette X, et al. Annals of the rheumatic diseases. 2014
Disclosure of Interest S. Das: None declared, J. Ferreira: None declared, M. Y. Md Yusof: None declared, E. Vital Grant/research support from: Roche and GSK., P. Emery Grant/research support from: Abbott, BMS, Pfizer, MSD and Roche., Consultant for: BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB.