Predictive Factors Of Response To Rituximab Therapy Modify The Accelerated Atherosclerosis In Patients With Rheumatoid Arthritis

Background Increased cardiovascular mortality has been associated with rheumatoid arthritis (RA). There are reports indicating that tumor necrosis factor blockers may exert favourable but transient effects on lipid profile, flow mediated vasodilation (FMD) of the brachial artery, and common carotid intima–media thickness (ccIMT) in RA. Objectives We evaluated 38 RA patients (33 females, 5 males) mean age 66.7±10.2, not responsive to TNFa blocking agents (mean number of previous anti TNFa agents 1.58±0.64). All patients were treated with Rituximab 1000 mg, days 1 and 15 (each cycle to assess the disease activity we evaluated at each visit: number of tender and swollen joints, global assessment, ESR mm/h,CRPmg/dl,DAS28,DAS28CRP,HAQ. Methods Disease activity was correlated with lymphocytes cluster differentiations CD3, CD4, CD8, CD19, CD20, CD38, CD56, CD45Ro/Ra cells/mL, rheumatoid factors IgM RF UI/ml, RF IgA U/ml, RF IgG U/ml, serum free light chains k and l levels, anti cyclic citrullinated peptide CC-P, immunoglobulins IgA, IgG, IgM mg/dl, ANA titres. Flow-mediated endothelium-dependent vasodilatation (FMD%) and endothelium-independent vasodilatation (postnitroglycerin) were measured at day 0 prior to the first RTX infusion, and at month 12. The statistical analysis was performed by software SAS System version 8.2. T–Student Test was performed to evaluate the variation of disease activity and a regression analysis was performed to evaluate the correlation between disease activity and haematological and serological parameters. Results At baseline tender joints were 6.88±1.99, swollen joints 5.15±1.64, Global Assessment 49.6±14.2, Ritchie Index 11.8±3.2, ESR 63.6±28.0 mm/h, CRP 2.5±1.8 mg/dl, DAS 5.78±0.8, DAS28 5.84±0.8, DAS28 CRP 5.05±0.9, HAQ 2.24±0.44 (mean ± SD).CD3 1343±779 cells/mL, CD4 993±653 cells/mL, CD8 335±185 cells/mL, CD19 122±85 cells/mL, CD20 109±68 cells/mL, CD38 82±54 cells/mL, CD56 350±302 cells/mL, CD45Ro 333±232 cells/mL, CD45Ra 248±231 cells/mL, IgA 272±136 mg/dL, IgG 1364±465 mg/dL, IgM 164±91 mg/dL, serum free light chains k 3.15±2 mg/dL, serum free light chains l 2.5±1.8 mg/dL, k/l ratio 1.2±0.4, ANA titres 224±269, RF IgM 318±590 UI/mL, RF IgA 101±154 U/mL, RF IgG 120±170 U/mL, anti- CCP 127±130 U/mL.Mean re-treatment time was 38.1±7.11 week. Total number of re-treatments was 49.A correlation between disease activity and CD19, Rheumatoid Factor-IgA levels and serum free light chains k levels was observed before every re-treatment.We evaluated at month 12, FMD % values in all patients (mean -SD 7.66 -1.73%, median 7.64%, range 5.61–9.98%) were greater than those found before the first infusion (P -0.03). The dramatic improvement of FMD % was associated with a significant decrease in CD19 lymphocytes,Disease Activity Score in 28 joints and IL-8 levels. Conclusions This study confirms that RTX reduces the progression of accelerated atherosclerosis in patients with RA and shows a correlation among ccIMT and FMD and CD19 levels, a marker of B cells involved in predicting the response to RTX. ccIMT and FMD showed also a correlation with disease activity score DAS28 and with IL-8 levels. Disclosure of Interest None Declared