LB0010 ULTRA-LOW DOSES OF RITUXIMAB OR RETREATMENT OF RHEUMATOID ARTHRITIS: A RANDOMISED CONTROLLED NON-INFERIORITY TRIAL
Authors: L.M. Verhoef, Nathan den Broeder, R.M. Thurlings, W.H. van der Laan, W. van der Weele, Marc Kok, H.J. Bernelot Moens, Thasia Woodworth, Bart van den Bemt, Frank van den Hoogen, Alfons den Broeder
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rituximab (RTX) is an effective treatment for patients with Rheumatoid Arthritis (RA). 1000mg (1 × 1000mg or 2 × 500mg) has similar 6-month efficacy as the registered dose of 2 × 1000mg. Based on several case reports and a case series even lower doses might be sufficient for maintenance treatment, potentially improving safety and decreasing costs.(1) <h3>Objectives</h3> To compare effectiveness of RTX retreatment with ultra-low doses (1 × 500mg or 1 × 200mg) to standard low dose (1 × 1000mg). <h3>Methods</h3> A 6-month double-blind randomised controlled non-inferiority trial (REDO study (2)) was performed in 5 centres in the Netherlands. Patients with RA responding well to RTX (based on DAS28-CRP&lt;2.9 or clinical judgement) were randomised (1:2:2) to 1 × 1000mg, 1 × 500mg or 1 × 200mg RTX respectively. DAS28-CRP and peripheral CD19+ B-cells were measured at baseline, 3 and 6 months. Primary analysis (per protocol with LOCF) consisted of a hierarchical testing procedure comparing ultra-low doses (1 × 500mg at 3 and 6 months, then 1 × 200mg at 3 and 6 months) to 1 × 1000mg using a non-inferiority margin of 0.6 (on DAS28-CRP). DAS28-CRP change of study groups was compared using linear regression, adjusted for baseline DAS28-CRP, RF/ACPA status and concomitant csDMARD use. <h3>Results</h3> The projected inclusion was met (n=142, table 1a). In both ultra-low dose groups 2 patients received an extra dose of 1000mg RTX due to a flare. The 500mg dose was non-inferior to 1000mg at 3 months (-0.04 (95% CI -0.39 to 0.30)), but not at 6 months (0.31 (95% CI -0.05 to 0.68). The 200mg dose was non-inferior to 1000mg at both time points. Because of our pre-defined hierarchical testing, non-inferiority could not formally be inferred for the 200mg dose. Mean DAS28-CRP scores remained low in all groups throughout the study, and B-cell counts decreased similarly at 3 months (figure 1). In the 200mg group, more patients received intramuscular corticosteroid injection(s) compared to the 1000mg group (table 1b). <h3>Conclusion</h3> Non-inferiority of retreatment with 1 × 500mg or 1 × 200mg rituximab versus 1 × 1000mg after 6 months could not formally be established. However, ultra-low doses appear similarly effective in the majority of RA patients, judged by DAS28-CRP course over time and B-cell results, with use of slightly more co-medication. <h3>References</h3> [1] Shenoy et al. Arthritis Rheumatol 2015;67(suppl 10). [2] Den Broeder et al. Trials 2017;30;18(1):403. <h3>Disclosure of Interests</h3> L.M. Verhoef: None declared, Nathan den Broeder: None declared, R.M. Thurlings Grant/research support from: Congress invitations: Roche, Abbvie, Cellgene, W.H. van der Laan: None declared, W. van der Weele: None declared, Marc Kok: None declared, H.J. Bernelot Moens: None declared, Thasia Woodworth: None declared, Bart van den Bemt Grant/research support from: UCB, Pfizer, Abbvie, Bristol-Myers Squibb, Consultant for: UCB, Novartis and Pfizer, Speakers bureau: Pfizer, AbbVie, UCB, Biogen, Sandoz, Frank van den Hoogen Grant/research support from: Grants, speakers fee, advisory boards: AbbVie, Actelion, Amgen, Boehringer Ingelheim, Biogen, BMS, Celgene, Celltrion Healthcare, Corbus, Janssen, Eli Lilly, Mundipharma, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme., Alfons den Broeder Grant/research support from: Congress invitations: Roche, Cellgene, Abbvie, Biogen, Consultant for: Expert Witness for Fresenius, BI, BMS, Amgen