Entecavir for Biological Agents Associated HBV Reactivation in Inflammatory Arthritis Patients

NCT ID: NCT01907230

Last Updated: 2019-03-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-10
• Study Completion Date: 2019-12-31

Brief Summary

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

Detailed 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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Entecavir, 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 (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).

Group Type: EXPERIMENTAL

Entecavir

Intervention Type: DRUG

In the prophylactic group, participants will initiate entecavir 0.5 mg/day orally one week before biologic treatment. Entecavir treatment (adjust dosage according to renal function) 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).

Control group (pre-emptive treatment)

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).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Entecavir

In the prophylactic group, participants will initiate entecavir 0.5 mg/day orally one week before biologic treatment. Entecavir treatment (adjust dosage according to renal function) 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).

Intervention Type: DRUG

Other Intervention Names

Baraclude

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taipei Veterans General Hospital, Taiwan

OTHER_GOV

Sponsor Role: lead

Responsible Party

vghtpe user

Professor: Yi-Hsiang Huang

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yi-Hsiang Huang, MD, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Taipei Veterans General Hospital, Taiwan

Locations

Division of Gastroenterology & Division of Allergy Immunology and Rheumatology, Taipei Veterans General Hospital

Taipei, , Taiwan

Countries

Taiwan

Other Identifiers

AI463-962

Identifier Type: -

Identifier Source: org_study_id