2.1 Basic Clinical Characteristics of Tocilizumab-treated Patients in FIB-reduced group.
A total of 94 patients who received TCZ treatment were included in this study, including 56 RA patients, 11 TA patients, 8 JIA patients, 5 SSc patients, 5 DM patients, 4 AOSD patients, and 3 BD patient, 1 UCTD patient, and 1 SIRS patient. All patients included were prescribed 8 mg/kg/month regularly, the median frequency of TCZ treatment was 6 (5-7) times. Among the tocilizumab-treatment patients, there were 32 patients (34.0%) in FIB-reduced group. There were 8 males and 24 females in FIB-reduced group, the median age was 32 (25-51) years, and the median disease duration was 2 years (3 months-7 years). Among the TA, RA, and JIA patients treated with TCZ, 7 (63.6%), 16 (28.6%), and 2 (25%) patients had FIB reduction, respectively. The mean baseline FIB in FIB-reduced group was 4.8g/l. (Table 1 and Supplementary Table 1 for details)
2.2 the Level of FIB in Plasma in FIB-reduced Group at Different Time Points
The vast majority of patients experienced FIB reduction within the first 3 months after receiving TCZ treatment (26 patients, 27.7%). Cumulatively, 9 patients (9.6%), 26 patients (27.7%) and 28 patients (29.8%) experienced FIB reduction after 1, 3, and 6 months of TCZ treatment (Figure 1A). Among RA patients, 8 patients (14.3%) and 15 patients (26.8%) experienced FIB reduction after 1 and 3 months of TCZ treatment, respectively. Among TA patients, 3 patients (27.3%) and 6 patients (54.5%) developed FIB reduction after 1 and 3 months of TCZ treatment (Figure 1B).
Of the 94 patients treated with TCZ, the lowest level of FIB was 0.78g/l. In FIB-reduced group, the mean (minimum-maximum) values of FIB level at baseline, 1month, 3months and 6 months after TCZ treatment were 4.80 (2.03-8.59), 2.25 (1.06-4.93), 1.74 (1.2-2.46) and 1.95 (1.32-3.51) g/l, respectively (normal range 2-4). Compared with baseline, the level of FIB in plasma after 1, 3 and 6 months of TCZ treatment reduced on average by 53.13%, 63.7% and 59.38%, respectively.
Of the 32 patients in FIB-reduced group receiving TCZ treatment, 21 (65.6%) patients had FIB returned to normal after median treatment time of 2.5 (4-6) months, and the remaining 11 patients (34.4%) had sustained FIB level below normal (Figure 2A-D). All patients in FIB-reduced group did not have ecchymosis, hematemesis, hemoptysis and thrombocytopenia, and received TCZ treatment regularly every month.
2.3 the Association between FIB and Other Acute Phase Proteins in RA patients treated with TCZ
At baseline, FIB was positively correlated with 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) (Figure 3A). The correlation analysis between FIB and other acute phase proteins (APP) after 1 month of TCZ treatment showed that FIB was positively correlated with ESR (r=0.709, p<0.05) (Figure 3B). The correlation analysis between FIB and other APP after 3 months of TCZ treatment showed that FIB was positively correlated with ESR (r=0.839, p<0.05), CRP (r=0.811, p<0.05) and hsCRP (r=0.830, p<0.05) (Figure 3C). The correlation analysis between FIB and other APP after 6 months of TCZ treatment showed that FIB was positively correlated with CRP (r=0.941, p<0.05) (Figure 3D). (Supplementary Data 2 for details)
34 (36.2%) patients suffered a decrease in C3 or C4 during the treatment period, among whom 26 (27.7%) patients suffered a decrease in C3, 24 (25.5%) patients suffered a decrease in C4, and 16 (17.0%) patients suffered a decrease in both C3 and C4 at the same time. (Supplementary Figure 1-2).
2.4 Comparison of Clinical Data between FIB reduced (RA) group and FIB normal (RA) group treated with TCZ.
Among RA patients treated with TCZ, B-lymphocyte counts were higher in RA patients in FIB-reduced (RA) group, compared with those in FIB-normal (RA) group (Supplementary Table 2). In the COX multivariate regression analysis, indexes with P≤0.2 in the COX univariate regression analysis were included, including swollen joint count (SJC), DAS28-CRP, white blood cell count (WBC), platelet count (PLT), total lymphocyte count, total T cell count, Th cell counts and B lymphocyte counts, the result showed that nor of the factors above were significantly associated with FIB reduction during TCZ treatment (Figure 4 and Supplementary Table 3).