Clinical trial NCT01907230: Entecavir for Biological Agents Associated HBV Reactivation in Inflammatory Arthritis Patients
Official title: Propylactic Use of Entecavir for Biological Agents Associated Hepatitis B Virus Reactivation in Inflammatory Arthritis Patients: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Hepatitis B Reactivation
Exposure to Hepatitis B Virus
Keywords: Rheumatoid arthritis
Inactive HBV carrier
Resolved Hepatitis B
HBV reactivation
Anti-tumor necrotic factor-alfa
Lead sponsor: Taipei Veterans General Hospital, Taiwan
Sponsor class: OTHER_GOV
First posted: 2013-07-24
Enrollment: 115
Sex: ALL
Minimum age (years): 20
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: HBV reactivation
timeFrame: 12 months after biologic treatment
Secondary outcomes:
measure: HBsAg reverse seroconversion in occult HB patients.
timeFrame: 12 months after biologic treatment
measure: Hepatitis flare (ALT > 100 U/L) related to biological treatments
timeFrame: 12 months after biologic treatment
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Division of Gastroenterology & Division of Allergy Immunology and Rheumatology, Taipei Veterans General Hospital
Study officials:
affiliation: Taipei Veterans General Hospital, Taiwan
name: Yi-Hsiang Huang, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: