Background:In emerging economies self-funding patients opt for less costly options, influencing both compliance and maintenance of treatment for chronic illness. Studies comparing originator rituximab 1000mgx2 and 500mgx2 doses in Rheumatoid arthritis (RA) have yielded interesting results1. Evidence of B cell depletion, measured by CD19 count, maybe a marker for disease improvement2. However effect of different dose of biosimilar Rituximab (bRTX) on B cell depletion and disease activity needs exploration.Objectives:To determine correlation of CD19 count defining B cell depletion and disease activity with different dosages of bRTX treatment.Methods:Between April 2019 and March 2020, all RA patients with DMARD failure were screened for eligibility of biologics as routine clinical practice. Depending on individual choice, after full consent, patients received either 1000mgx2 or 500mgx2 bRTX. All patients had CD19 count before and 12 months after the first dose. Effectiveness of bRTX 1000 mg×2 and 500 mg×2 was assessed by DAS28 and EULAR response. Comparative adjusted analysis was performed by analysis of variance (ANOVA).Results:Out of 468 eligible patient, 84 opted for biologic. Of which 27 patients consented for bRTX (17 female, mean age 39.5 years).13 patients opted for 1000mg×2 and 14 for 500mg×2 dose. 74% (20/27) patients were on concomitant methotrexate and 26% on hydroxychloroquine (7/27). Both doses led to significant reduction in ESR, CRP, and DAS28-ESR at 12 months (p<0.001) (Table 1).Table 1.RA outcome-measurement scores at 12 months post biosimilar Rituximab therapy.VariableBaseline12 monthsRTX 1000mg x 2(n=13)RTX 500mg x 2(n=14)RTX 1000mg x 2(n=13)RTX 500mg x 2(n=14)ESR*53.9±23.957.1±24.723.9±2.924.1±4.7CRP*6.1±3.96.9±2.92.1±0.92.3±0.9DAS28-ESR*6.1±0.36.1±0.24.0±0.44.1±0.2CD 19+ Count*# (105/L)1191.6±308.41155±289.6128.8±90.4139±90.6* p<0.0001 as compared to 12 mos vs baseline; # p<0.0001 as compared amongst groupAt the end of 12 months, compared to 1000mg, CD19 count was higher in 500mg group (p=0.25). Percentage of patients achieving EULAR moderate or no response was higher in 500mg group (37%vs29%, p=0.205), both complete and incomplete B cell depletion, but patients achieving good response was same in both groups (14.8%vs18.5%, p = 0.25). (Figure 1).Figure 1.EULAR Response at 12 monthsConclusion:Low dose bRTX is effective in DMARD refractory RA patients with similar improvements as regular dose, although CD19 depletion was less in low dose group. A larger study to establish radiographic regression with CD19 depletion and disease activity score can help in further strengthening the use of lower dose bRTX in RA leading to significant economic advantage.References:[1]Chatzidionysiou K, Lie E, Nasonov E, Lukina G,et al. Rheumatic Diseases Portuguese Register. Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort: data from the CERERRA collaboration. Arthritis Res Ther. 2016 Feb 16;18:50.[2]Vital EM, Rawstron AC, Dass S, Henshaw K, Madden J, Emery P, McGonagle D. Reduced-dose rituximab in rheumatoid arthritis: efficacy depends on degree of B cell depletion. Arthritis Rheum. 2011 Mar;63(3):603-8.Disclosure of Interests:None declared
Biomarkers of Good EULAR Response to the B Cell Depletion Therapy in All Seropositive Rheumatoid Arthritis Patients: Clues for the Pathogenesis
