Entecavir for Biological Agents Associated HBV Reactivation in Inflammatory Arthritis Patients

Taipei Veterans General Hospital

Status and phase: Unknown; Phase 4

Conditions: Exposure to Hepatitis B Virus; Hepatitis B Reactivation; Rheumatoid Arthritis

Treatments: Drug: Entecavir

Study type: Interventional

Funder types: Other

Identifiers

NCT01907230

AI463-962

Details and patient eligibility

About

Antiviral prophylaxis can prevent the risk of biologic agents-associated HBV reactivation in hepatitis B inactive carriers and patients with past HBV infection

Full description

The risk of HBV reactivation is associated with the intensity of immunosuppression. Biological therapies block the action of biological products involved in immune-inflammatory pathogenesis of many diseases. However, these biologic agents induce a profound immunosuppression, and their use has been reported to be associated with HBV reactivation. Currently, the actual incidence of HBV reactivation in inflammatory arthritis patients who underwent biologic treatments (TNF-α blockades) is unclear, especially in inflammatory arthritis (IA) patients with past hepatitis B infection. In this study, we plan to enroll IA patients who are inactive HBV carriers (HBsAg-positive/ HBV viral loads <2000 IU/ml; subgroup 1), or have past HBV infection (HBsAg-negative/anti-HBc-positive/ HBV viral loads < 2000 IU/ml; subgroup 2); and first line biologic treatment (Humira or Enbrel or Simponi or Orencia or Mabthera or Actemra) is indicated. Patients will be randomized in a 1:1 ratio to receive either prophylactic or therapeutic entecavir treatment for each subgroup. In the prophylactic group, participants will initiate entecavir 0.5 mg/day orally one week before biologic treatment. Entecavir treatment will be continued normally for 12 months. In the therapeutic group, patients will start entecavir therapy, 0.5 mg/day orally, when reactivation of HBV (pre-emptive treatment). HBV reactivation is defined as HBV viral loads > 2,000 IU/ml for 2 consecutive visits of one month apart. The main goal of the study is to delineate the incidence of HBV reactivation during and after biologic treatment in IA patients who are inactive HBV carriers or have past HBV infection, and tries to define the optimal HBV monitoring and antiviral prophylactic strategy in IA patients.

Enrollment: 115 patients

Sex: All

Ages: 20 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age : from 20 to 90 y/o.
2. HBsAg-positive for more than 6 months and HBV DNA < 2000 IU/ml (Subgroup 1）or HBsAg-negative but anti-HBc positive with HBV DNA < 2000 IU/ml (Subgroup 2）.
3. Inflammatory arthritis patients who plan to treat with biological agents, including Humira or Enbrel or Simponi or Orencia or Mabthera or Actemra; as first line biologic treatment is indicated.

Exclusion criteria

1. HCV, HIV, or HDV coinfection.
2. Uncontrolled HCC or other malignancy within 3 years.
3. Decompensated liver cirrhosis (CTP score ≥ 7).
4. Uremia patients under hemodialysis or continuous ambulatory peritoneal dialysis or patients with Ccr < 50 mL/min
5. Pregnant or breastfeeding women.
6. Women of child-bearing potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study drug.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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115 participants in 2 patient groups

Entecavir, Prophylactic group

Experimental group

Description:

Participants will initiate entecavir 0.5 mg/day orally one week before biologic treatment. Entecavir treatment will be continued normally for 12 months (6 months after stopping biologic therapy or till restart another course of biologic treatment if the clinicians' judgment is minimal risk of reactivation after the first course of biologic agent treatment).

Treatment:

Drug: Entecavir

Control group (pre-emptive treatment)

No Intervention group

Description:

Patients will start entecavir therapy, 0.5 mg/day orally, when reactivation of HBV (defined as detectable HBV viral loads for 2 consecutive visits with at least one month apart), and continued entecavir treatment until undetectable HBV viral loads for 1 year (consistent with current APASL recommendation).