Entecavir for Biological Agents Associated HBV Reactivation in Inflammatory Arthritis Patients

Phase 4UnknownNCT01907230

Taipei Veterans General Hospital, Taiwan115 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

115

Conditions

Rheumatoid Arthritis Hepatitis B Reactivation Exposure to Hepatitis B Virus

Interventions

EntecavirDRUG

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).

Eligibility

Sex: ALLMin age: 20 YearsMax age: 90 Years

Medical Language ↔ Plain English

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.

Locations (1)

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

Taipei, Taiwan

Outcomes

Primary Outcomes

HBV reactivation

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.

Time frame: 12 months after biologic treatment

Secondary Outcomes

HBsAg reverse seroconversion in occult HB patients.

Time frame: 12 months after biologic treatment

Hepatitis flare (ALT > 100 U/L) related to biological treatments

Time frame: 12 months after biologic treatment

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.