The Efficacy of TAF as a Prophylactic Antiviral Agent for HBsAg-positive Patients Receiving Biological DMARDs (bDMARDs)
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 108
- 主要终点
- 1-year HBV reactivation rate
研究概览
简要总结
Hepatitis B virus reactivation (HBVr) is an emerging issue and a potentially life-threatening complication to patients with history of Hepatitis B virus (HBV) infection whose immune system is deficient or suppressed. It is estimated that the risk of HBVr ranges 20%-50% in hepatitis B surface antigen (HBsAg)-positive patients undergoing chemotherapy or immunosuppressive therapy. Not only HBsAg-positive patients but also HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive patients (resolved hepatitis B) have the risk of HBVr.
Recent studies also reported that the risk of HBVr associated with TNF-α inhibitor treatment widely ranged from 12.3% to 62.5%. Antiviral prophylaxis by nucleos(t)ide analogues (NUCs) is recommended for patients with high risk of HBVr according to 2018 AASLD guidance. Phase 3 studies reported that tenofovir alafenamide (Vemlidy, TAF) can effectively suppress HBV in both HBeAg-positive and HBeAg-negative chronic hepatitis B patients, and TAF is superior to TDF in safety profiles and ALT normalization. However, the evidence of TAF in prevention HBV reactivation for patients with HBsAg-positive and imflammatory arthritis, who need bDMARDs are still missing.
详细描述
Hepatitis B virus (HBV) infection is the major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. There are up to 248 million people worldwide chronically infected with HBV. HBV reactivation (HBVr) is an emerging issue and a potentially life-threatening complication to patients with history of HBV infection whose immune system is deficient or suppressed. It is estimated that the risk of HBVr ranges 20%-50% in hepatitis B surface antigen (HBsAg)-positive patients undergoing chemotherapy or immunosuppressive therapy. Not only HBsAg-positive patients but also HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive patients (resolved hepatitis B) have the risk of HBVr. The investigator's studies have demonstrated that the risk of HBsAg seroreversion was 10% in diffuse large B cell lymphoma patients undergoing anti-CD20 (rituximab) treatment; and the risk of HBsAg reverse seroconversion in rheumatic arthritis (RA) patients with resolved HBV infection and received biological disease-modifying antirheumatic drugs (bDMARDs) or glucocorticoid (GC) treatment can persist for up to 10 years. In the investigator's previous study, it also be investigated the risk of HBVr under different immunosuppressant regimens in HBsAg-positive patients with RA, and the investigator pointed out immunosuppressive treatment with a combination of GC, synthetic disease-modifying antirheumatic drugs (sDMARDs), and bDMARDs has the highest risk of HBVr with annual incidence around 20%. Recent studies also reported that the risk of HBVr associated with TNF-α inhibitor treatment widely ranged from 12.3% to 62.5%.
Antiviral prophylaxis by nucleos(t)ide analogues (NUCs) is recommended for patients with high risk of HBVr according to 2018 AASLD guidance. Phase 3 studies reported that tenofovir alafenamide (Vemlidy, TAF) can effectively suppress HBV in both HBeAg-positive and HBeAg-negative chronic hepatitis B patients, and TAF is superior to TDF in safety profiles and ALT normalization. However, the evidence of TAF in prevention HBV reactivation for patients with HBsAg-positive and imflammatory arthritis, who need bDMARDs are still missing. Therefore, the investigator plans to conduct this randomized controlled trial to confirm the efficacy of TAF as a prophylactic antiviral agent for HBsAg-positive patients with inflammatory arthritis (IA) on bDMARDs treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >=20 years old;
- •History of chronic hepatitis B with HBsAg-positive;
- •Both HBeAg-positive and HBeAg-negative are allowed;
- •Inflammatory arthritis (including psoriatic arthritis);
- •On bDMARDs treatment or will start bDMARDs within in 4 weeks. The bDMARDs included all anti-TNF-α agents, rituximab (anti-CD20 monoclonal antibody), tocilizumab (anti-interleukin 6 receptor monoclonal antibody), abatacept (cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin), and all new biologics with indication of IA treatment;
- •No NUCs treatment in recent 6 months;
- •No limitation of the baseline HBV DNA level;
- •Total bilirubin level <2 mg/dL;
- •ALT < 2x ULN (<80 U/L).
排除标准
- •Child-Pugh class >B7;
- •Active EV bleeding within 4 weeks;
- •History of hepatic encephalopathy or intractable ascites;
- •Coexist with other primary liver diseases, such as active chronic hepatitis C, hepatitis D, autoimmune hepatitis, or Wilson's disease. (*HCV RNA undetectable is allowed to enroll);
- •Active malignancy;
- •Pregnant women.
研究组 & 干预措施
TAF arm
54 patients will be randomized into TAF arm*. TAF 25 mg QD will be initiated 7 days before bDMARDs, and continued for up to 144-weeks.
*for patients received rituximab (anti-CD20 monoclonal antibody) will be enrolled into TAF arm, and TAF 25 mg QD will be initiated 7 days before rituximab, and continued for up to 144-weeks. Max 20 rituximab patients will be recruited.
干预措施: Tenofovir alafenamide (Drug)
Observation arm
54 patients will be randomized into observation arm initially. These patients will be closely monitored their HBV status (including qHBsAg and HBV DNA) for 48 weeks. TAF 25 mg QD will be initiated for 144 weeks in the presence of HBV reactivation, or after 48 weeks of observation.
干预措施: Tenofovir alafenamide (Drug)
结局指标
主要结局
1-year HBV reactivation rate
时间窗: Up to 1-year
The assessment for the HBV reactivation is by the marker as hepatitis b viral load (unit: IU/ML).
次要结局
- The 1-year virological remission rate(Up to 1-year)
- The adverse reactions and compliance(Up to 3-years)
- Observation of bone mineral density at 48-weeks, 96-weeks, and 144-weeks(Up to 3-years)
- Serial change of renal and liver function(Up to 3-years)
- The 1-year HBeAg seroconversion rate(Up to 1-year)