Clinical trial NCT05001672: The Efficacy of Prophylactic TAF for HBsAg-positive Patients Receiving bDMARDs
Official title: The Efficacy of TAF as a Prophylactic Antiviral Agent for HBsAg-positive Patients Receiving Biological DMARDs (bDMARDs)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: HBV
Inflammatory Arthritis
Lead sponsor: Taipei Veterans General Hospital, Taiwan
Sponsor class: OTHER_GOV
First posted: 2021-08-12
Enrollment: 108
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients who fulfilled in all inclusion and exclusion criteria will be randomized into TAF 25mg qd or observation arm in 1:1 ratio.

* 54 patients will be randomized into TAF arm\*.
* 54 patients will be randomized into observation arm initially.
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.

Primary outcomes:
measure: 1-year HBV reactivation rate
timeFrame: Up to 1-year
Secondary outcomes:
measure: Serial change of renal and liver function
timeFrame: Up to 3-years
measure: Observation of bone mineral density at 48-weeks, 96-weeks, and 144-weeks
timeFrame: Up to 3-years
measure: The 1-year virological remission rate
timeFrame: Up to 1-year
measure: The 1-year HBeAg seroconversion rate
timeFrame: Up to 1-year
measure: The adverse reactions and compliance
timeFrame: Up to 3-years
Other outcomes:
Locations:
Study officials:
References: