title: [Liver safety of biosimilar of recombinant tumor necrosis factor-α receptor-antibody fusion protein in Spondyloarthritis patients under different status of HBV infection: a prospective observational study].
abstract: OBJECTIVE
  To investigate the influence of recombinant human tumor necrosis factor α receptor-antibody fusion protein (rhTNFR: Fc) to the Hepatitis B virus (HBV) infection status and liver function of Spondyloarthritis (SpA) patients under different HBV infection status.
  
  
  METHODS
  Active SpA patients with normal liver function were enrolled in Sun Yat-sen Memorial hospital from February 2012 to August 2014. All were treated with rhTNFR: Fc based therapy (monotherapy or combined therapy) for at least 12 weeks. SpA disease activity, HBV infection status and liver function were evaluated at each interview (baseline, 4(th) and 12(th) week, as primary endpoint). Part of the patients were evaluated at 24(th) week with or without extended rhTNFR: Fc treatment(as secondary endpoint) based on their choice.
  
  
  RESULTS
  Eighty-one patients who completed 12-week follow-up visit were divided into chronic HBV carrier group (n=21), past HBV exposure group (n=25) and free of HBV infection group (n=35). Alanine transaminase (ALT) elevated (no more than 3-fold of normal) in 3 patients from 3 groups respectively at 4th week. During 24-week follow-up, none in past HBV exposure group or in free of HBV infection group developed HBV reactivation or HBV infection; and 4 patients in chronic HBV carrier group developed HBV reactivation without more than 2-fold of normalelevation of ALT. Among 7 patients with negative baseline HBV-DNA and without antiviral prophylaxis, 2 patients developed HBV reactivation at 10(th) 24(th) week of rhTNFR: Fc therapy respectively and 1 patient developed reactivation at 16(th) week (12-week rhTNFR: Fc+ thalidomide therapy and following 4-week thalidomide monotherapy), whose HBV-DNA load returned to normal spontaneously or after antiviral therapy. Four chronic HBV carriers with low-load of baseline HBV-DNA did not develop reactivation. One of 9 chronic HBV carriers with high-load of baseline HBV-DNA developed reactivation due to resistance of antiviral prophylaxis.
  
  
  CONCLUSIONS
  Short-term rhTNFR: Fc based therapy may induce mild and transient HBV reactivation, usually without hepatitis.
authors.affiliation: Department of Rheumatology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.forename: Yingqian
authors.initials: Y
authors.lastname: Mo
authors.forename: Jinjian
authors.initials: J
authors.lastname: Liang
authors.forename: Qiyang
authors.initials: Q
authors.lastname: Sun
authors.forename: Yueting
authors.initials: Y
authors.lastname: Huang
authors.forename: Donghui
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Email: liedai2004@163.com.
authors.forename: Lie
authors.initials: L
authors.lastname: Dai
mesh_terms: D000410:Alanine Transaminase; D000998:Antiviral Agents; D059451:Biosimilar Pharmaceuticals; D006509:Hepatitis B; D006515:Hepatitis B virus; D006801:Humans; D008099:Liver; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins; D025241:Spondylarthritis; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000998:Antiviral Agents; D059451:Biosimilar Pharmaceuticals; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins; C506235:TNFRSF1A protein, human; D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase