| Aim:To observe the curative effects and adverse events of tumor necrosis factor(TNF)? antagonists by intra-articular injection in the treatment of hemophilic synovitis.Methods: Twenty-eight hemophilic synovitis patients with 32 “target joints” were enrolled in treatment group.A single dose of 25 mg of Etanercept(Recombinant Human Tumor Necrosis Factor-? Receptor?:Ig G Fc Fusion Protein for Injection)was injected into the cavity of each target joint.The bleeding frequency(times/month),visual analogue score(VAS)for joint pain,Hemophilia Joint Health Score(HJHS)and Ultrasound Score(HEAD-US-C Score)for the target joints were collected before injection(D0)and on one months(D30)and three months(D90)post injection.The synovial thickness and vascularity of the fixed section of the treated joint were monitotred by ultrasound and power doppler before and at each follow-up.Adverse events(AEs)were reported by patients and recorded.The levels of TNF-? in serum and synovial fluid were measured by ELISA method.A total of 50 joints from 14 hemophiliac patients who were on prophylaxis or on-demand coagulation factor therapy were selected as the control group,in order to observe the natural courses of the synovial thickness changes without anti-TNF? therapy.Results:(1)Demographic data: A total of 28 patients with 32 hemophilic synovitis joints were selected as treatment group,which including 18 knee joints,7 ankle joints,and 7 elbow joints.All patients were male,with a median age of 24 years(range 11-43years).The median follow-up time was 7 months(range 3-12 months).Fourteen patients with hemophilia were selected as the control group,and 50 joints,including 22 knee joints in 13 patients,10 ankle joints in 6 patients,and 18 ankle joints in 11 patients were observed.The median follow-up time for the knee,ankle,and elbow joints were 6months(3 to 11 months),5 months(3 to 12 months),and 8 months(3 to 12 months).(2)Clinical and ultrasound data at the D30 of follow-up: one patient(one joint)was lost to follow-up due to poor self-consciousness.The remaining 31 target joints responded to treatment with a response rate of 96.8%(31/32 joints).Compared with before treatment(D0),the bleeding frequency was reduced(2.9±1.4 times / month vs1.2±1.4 times / month,P <0.05);VAS score decreased(5.5±1.3 vs 2.7±1.3,P <0.05);HJHS score decreased(8.5±2.9 vs 7.4±2.8,P <0.05);HEAD-US-C score decreased(8.3±2.1 vs 7.7±2.1,P <0.05).Synovial thickness in area with maximum,mean synovial thickness of all evaluated areas and synovial thickness in area with maximum change were decreased by 22.2%,18.9%,34.7%.Compared with D0,the proportion of synovial vascularity grade 0 increased(16.5% vs 31.5%),grade 1(31.5% vs 27.6%)and grade 2(28.3% vs 29.9%)no significant change,and grade 3 decreased(23.6% vs11.0%),which confirmed that the vascularity of the synovial joints were reduced.The synovial thickness and vascularity of 50 joints in 14 patients of the control group was no significant variation throughout of the follow-up period.(3)Clinical and ultrasound data at the D90 of follow-up: 14 patient(16 joint)was lost to follow-up due to poor self-consciousness.The remaining 31 target joints responded to treatment with a response rate of 50%(16/32 joints).Compared with before treatment(D0),the bleeding frequency was reduced(2.9±1.3 times / month vs1.2±0.8 times / month,P <0.05);VAS score decreased(5.6±0.9 vs 1.8±1.3,P <0.05);HJHS score decreased(8.9±2.9 vs 7.2±2.9,P <0.05);HEAD-US-C score decreased(8.2±2.2 vs 7.5±2.2,P <0.05).Synovial thickness in area with maximum,mean synovial thickness of all evaluated areas and synovial thickness in area with maximum change were decreased by 27.4%,26.2%,40.7%.Compared with D0,the proportion of synovial vascularity grade 0 increased(22.2% vs 54.4%),grade 1 decreased(38.2% vs22.1%),grade 2(23.5% vs 23.5%)no significant change,and grade 3 reductions decreased(16.2% vs 0.0%),which confirmed that the vascularity of the synovial joints were reduced.The synovial thickness and vascularity of 50 joints in 14 patients of the control group was no significant variation throughout of the follow-up period.(4)TNF-? was increased(175.6±319.8ng/ml)in synovial fluid samples which were successfully collected from 9 patients of treatment group;The decrease of synoviallevels of TNF-? after treatment(24.7±9.2ng/ml)were observed in 6 patients,and a fluctuant TNF-? levels were in two patients with decreased significantly afterwards.(5)No severe adverse events was occurred during the follow-up period.Joint swelling in ankle post injection were reported by two patients,no other AEs,such as fever,pain in the injection sites,infection etc were reported.Conclusion:Our data showed intraarticular injection of TNF-? antagonist is an effective and safe adjunctive therapy method for patients with hemophilic synovitis. |
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