title: Safety of etanercept and methotrexate in patients with rheumatoid arthritis and hepatitis C virus infection: a multicenter randomized clinical trial.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of therapy with etanercept and methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and mild hepatitis C virus (HCV) infection.
  
  
  METHODS
  In this prospective open study, 29 patients with active RA were randomly assigned to receive therapy with MTX alone, etanercept alone, or a combination of MTX and etanercept, and monitored up to 54 weeks. The primary endpoint was safety; secondary aims were efficacy as defined by the 44-joint Disease Activity Score (DAS44) and health assessment questionnaire (HAQ). Serum liver enzymes and HCV viral load were serially measured.
  
  
  RESULTS
  In the whole cohort, aspartate aminotransferase (AST) serum levels were (mean ± SD) 35 ± 3 at entry, 39 ± 5, 41 ± 7, and 38 ± 4 at 14, 30, and 54 weeks, respectively; alanine aminotransferase (ALT) serum levels were 43 ± 5 at entry, 47 ± 5, 53 ± 9, and 50 ± 6 at 14, 30, and 54 weeks, respectively. HCV viral load was 5.6 ± 0.5 at entry, 5.9 ± 0.6, 5.7 ± 0.3, and 5.6 ± 0.6 at 14, 30, and 54 weeks, respectively. AST and ALT did not significantly change in all 3 arms of treatment, nor did HCV viral load. A significant reduction of DAS44 (p < 0.01) and HAQ (p < 0.04) was detected at 54 weeks compared to baseline. No patient discontinued the therapy because of worsening of liver disease.
  
  
  CONCLUSIONS
  This study showed that patients with RA and chronic HCV and mild hepatitis may be successfully treated with etanercept and MTX without increasing the risk of hepatotoxicity and HCV replication. ClinicalTrials.gov Identifier NCT01543594.
authors.affiliation: From the Interdisciplinary Department of Medicine, Rheumatology Unit, Bari; Rheumatology Unit, II University of Naples, Naples; Rheumatology Unit, Messina; Università Cattolica del Sacro Cuore, Rome; Rheumatology Unit, University of Palermo, Italy.
authors.forename: Florenzo
authors.initials: F
authors.lastname: Iannone
authors.forename: Giovanni
authors.initials: G
authors.lastname: La Montagna
authors.forename: Gianfilippo
authors.initials: G
authors.lastname: Bagnato
authors.forename: Elisa
authors.initials: E
authors.lastname: Gremese
authors.forename: Annarita
authors.initials: A
authors.lastname: Giardina
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lapadula
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001219:Aspartate Aminotransferases / Q000097:blood; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D016174:Hepacivirus; D006526:Hepatitis C / Q000097:blood / Q000150:complications*; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use; D008111:Liver Function Tests; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000068800:Etanercept; D008727:Methotrexate
keywords: DISEASE ACTIVITY SCORE; GISEA; HEALTH ASSESSMENT QUESTIONNAIRE; TNF-α INHIBITORS; TRANSAMINASES