Clinical and ultrasonic remission of rheumatoid arthritis after being treated uith tocilizumab for three months / 中华风湿病学杂志

ABSTRACT

Objective:To observe the changes of relevant clinical indicators and ultrasound pre-sentations in rheumatoid arthritis (RA) patients after being treated with tocilizumab for 3 months and explore the efficacy and safety of tocilizumab in the treatment of RA.Methods:Clinical data, laboratory and ultrasound examinations and medications of RA patients who met inclusion criteria in our hospital from Jan-uary 2017 to September 2020 were included and their data were analyzed retrospectively, and the efficacy and safety of tocilizumab and the ultrasound assessment of disease remission were analyzed. Paired sample t test, Wilcoxon signed-rank test, χ2 test or Fisher's exact probability test were used for comparative analysis. Results:① Compared with baseline data, morning stiffness duration of patients treated with tocilizumab for 3 months [60(30, 120) min vs 0(0, 10) min, Z=-6.19, P<0.001], disease activity score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR) [(4.6±1.5) vs (3.2±1.2), t=6.83, P<0.001], disease activity score of 28 joints-C-reactive protein (DAS28-CRP) [(4.2±1.4) vs (2.8±1.1), t=7.14, P<0.001], swollen joint count (SJC) [2(1, 7) vs 0(0, 2), Z=-4.31, P<0.001], tender joints count (TJC) [6(2, 13.5) vs 2(0,4), Z=-5.16, P<0.001], gray scale score (GS) [4.5(2, 6) vs 1(0, 3), Z=-5.86, P<0.001], intra-synovial blood flow energy Doppler (PD) [2(1, 3) vs 0(0, 0), Z=-5.38, P<0.001], white blood cell (WBC) [6.6(4.9, 8.4)×10 9/L vs 5.7(4.9, 7.3)×10 9/L, Z=-2.83, P=0.005], hemoglobin (Hb) [119(104, 131) g/L vs 123(113, 136) g/L, Z=-2.82, P=0.007], ESR [32(14.5, 50) mm/1 h vs 19 (10, 30) mm/1 h, Z=-3.31, P=0.001], CRP [11.40(3.02, 25.80) mg/L vs 3.49(1.30, 11.82) mg/L, Z=-2.78, P=0.004], D-dimer (D-D) [0.93(0.47, 2.07) mg/L vs 0.43(0.21, 0.80) mg/L, Z=-3.77, P<0.001] were significantly improved, and the difference was statistically significant. ② The serum levels of interleukin (IL)-2 [2.08(1.43, 2.76) pg/ml vs 1.21(0.54, 2.08) pg/ml, Z=-2.67, P=0.008], IL-6 [22.40(5.13, 67.27) pg/ml vs 14.63(5.27, 27.71) pg/ml, Z=-2.81, P=0.005], IL-10 [(2.53±0.68) pg/ml vs (1.74±0.74) pg/ml, t=2.60, P=0.017] were significantly changed, while serum levels of IL-4 [1.63(1.08, 3.38) pg/ml vs 1.33(0.97, 2.59) pg/ml, Z=-0.89, P=0.374], tumor necrosis factor (TNF) -α [4.04(1.41, 10.45) pg/ml vs 1.62(0.84, 3.79) pg/ml, Z=-1.92, P=0.056], IL-17 [4.68(1.67, 6.72) pg/ml vs 3.15(1.81, 5.29) pg/ml, Z=-0.53, P=0.594] were not significantly changed from baseline data. ③ There was poor consistency between ultrasonic response and DAS28-ESR response, simplified disease activity Index (SDAI) response and clinical disease activity index (CDAI) response ( Kappa coefficient 0.142, 0.142, 0.191), but no consistency between ultrasonic response and DAS28-CRP response (Kappa coefficient -0.015) were found. Receiver operating characteristic (ROC) curve showed that ultrasound was not statistically significantly different in assessing the remission of RA, indicating subclinical synovitis remained in ultrasound examination even though clinically remission could be reached based on the above scoring indexes in RA patients. ④ In terms of adverse reactions, neutrophils (NEU) of patients after 3 months' tocilizumab treatment [4.47(2.77, 5.39)×10 9/L vs 3.76(2.98, 4.74)×10 9/L, Z=-2.77, P=0.006], platelet count (PLT) [(291±84)×10 9/L vs (254±70)×10 9/L, t=4.76, P<0.001] were significantly decreased, high-density lipoprotein-cholesterol (HDL-C) [(1.22±0.27) mmol/L vs (1.39±0.34) mmol/L, t=3.12, P=0.003], low density lipoprotein-cholesterol (LDL-C) [(1.96±0.66) mmol/L vs (2.19±0.84) mmol/L, t=3.15, P=0.003], triglyceride (TG) [0.85(0.68, 1.08) mmol/L vs 0.93(0.71, 1.25) mmol/L, Z=-2.36, P=0.018] and total cholesterol (TC) [(4.18±1.04) mmol/L vs (4.52±1.16) mmol/L, t=3.33, P=0.002] were significantly different from baseline. Among 65 patients, 5 patients (7.7%) had transaminase abnormality, but returned to normal after symptomatic treatment. Conclusion:Tocilizumab treatment can effectively suppress the inflammatory reactions, improve the clinical symptoms and prognosis of patients, however, patients who judged as clinical remission according to the current clinical commonly scores may still have subclinical active disease, ultrasound results should be included as one criteria for disease remission assessment and take into consideration when adjusting treatrnent.