Clinical observation of hypofibrinogen induced by the treatment of tocilizumab in rheumatic disease

Abstract Background : By analyzing the changes of fibrinogen levels in plasma during tocilizumab-treated patients with rheumatic diseases, and the aim was to clarify the incidence and possible influencing factors of hypofibrinogenemia. Methods : These tocilizumab-treated patients with rheumatic diseases in the First Affiliated Hospital of Xi 'an Jiaotong University from January 2014 to October 2021 were included, to observe the reduced level of fibrinogen (FIB) in plasma at different time points in different diseases, explore the correlation between FIB and other acute phase proteins including Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), high-sensitivity C-reactive protein (hsCRP) in rheumatoid arthritis (RA) patients, and explore the risk factors for FIB reduction among RA patients treated with tocilizumab(TCZ) by COX regression. Results : A total of 94 tocilizumab-treated patients were included in this study. The median frequency of TCZ treatment was 6 (5-7) times, and 32 patients (34.0%) suffered FIB reduction during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with a median age of 32 (25-51) years. Hypofibrinogen is most common in patients with Takayasu arteritis (TA) and Rheumatoid Arthritis (RA) treated with TCZ, with an incidence of 63.6% and 28.1%, respectively. In RA patients treated with TCZ, FIB at baseline was positively correlated with acute phase protein ESR (r=0.594, p<0.001), CRP (r=0.593, p<0.001), hsCRP (r=0.564, p<0.001) and C3 (r=0.462, p<0.05). There was a positive correlation between FIB and CRP after 3 months of TCZ treatment (r=0.811, p<0.05), and after 6 months of TCZ treatment (r=0.941, p<0.05). Further COX regression analysis did not find any factors associated with FIB reduction to reach statistical significance. Conclusion : The incidence of FIB reduction was high after TCZ treatment. FIB was correlated with acute phase proteins before and during treatment.