Entecavir for Biological Agents Associated HBV Reactivation in Inflammatory Arthritis Patients

Phase 4

• Conditions: Exposure to Hepatitis B Virus; Hepatitis B Reactivation; Rheumatoid Arthritis
• Interventions: Drug: Entecavir

• Registration Number: NCT01907230
• Lead Sponsor: Taipei Veterans General Hospital, Taiwan

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.

Study Timeline

• Study First Submitted: 2013-07-14
• Study First Submitted QC: 2013-07-18
• Study First Posted: 2013-07-24
• Study Start: 2013-09-10
• Primary Completion: 2018-12-31
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-11
• Last Update Posted: 2019-03-13
• Study Completion: 2019-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 115

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Entecavir, Prophylactic group	Entecavir	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).

Primary Outcome Measures

Name	Time	Method
HBV reactivation	12 months after biologic treatment	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.

Secondary Outcome Measures

Name	Time	Method
Hepatitis flare (ALT > 100 U/L) related to biological treatments	12 months after biologic treatment
HBsAg reverse seroconversion in occult HB patients.	12 months after biologic treatment

Trial Locations

Locations (1)

Division of Gastroenterology & Division of Allergy Immunology and Rheumatology, Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan