title: Off-label use of tumour necrosis factor-alpha inhibitors and anakinra at an Australian tertiary hospital.
abstract: BACKGROUND
  Tumour necrosis factor-alpha inhibitors (anti-TNFα) and anakinra are monoclonal antibodies against pro-inflammatory cytokines overexpressed in many systemic inflammatory diseases. In Australia, they are registered for the treatment of several rheumatological, gastroenterological and dermatological indications. Despite increasing observational evidence for their use in off-label indications, there is a paucity of outcome research from the Australian hospital sector.
  
  
  OBJECTIVE
  To describe the off-label use of anti-TNFα and anakinra at a tertiary referral hospital in Queensland, Australia and consideration of a drug register to inform future clinical decision-making.
  
  
  METHODS
  We performed an in-depth retrospective chart audit of off-label treatment with anti-TNFα or anakinra at the Royal Brisbane and Women's Hospital from mid-2010 to mid-2014, linking demographic, phenotypic, pathology and outcome data with these drugs.
  
  
  RESULTS
  Off-label use was identified in 10 patients. The most frequent indications were sarcoidosis and dermatological conditions. Three patients required sequential therapy with a second anti-TNFα (total responses = 13). Complete response occurred in 46%, partial response in 38% and primary non-response in 8%. Response was unable to be determined in 8%. We recorded 14 adverse events (infections most common).
  
  
  CONCLUSIONS
  This study suggests that anti-TNFα may be beneficial for some off-label indications (e.g. sarcoidosis). However, the observational design of this study (and pre-existing research) limits the ability to infer causality and generalise results. We propose the creation of a mandatory drug register to monitor off-label use. Whilst comparative efficacy cannot be established without a matched placebo arm, a register would enable some reporting on effectiveness in rare diseases and identify infrequent but serious adverse events.
authors: Schools of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
authors: M W
authors: MW
authors: Linger
authors: Schools of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
authors: M L
authors: ML
authors: van Driel
authors: School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
authors: S A
authors: http://orcid.org/0000-0002-5226-5663
authors: SA
authors: Hollingworth
authors: School of Medicine and Public Health, The University of Newcastle, Newcastle, New South Wales, Australia.
authors: J H
authors: JH
authors: Martin
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001315:Australia; D000066491:Clinical Decision-Making; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D008297:Male; D056687:Off-Label Use; D018579:Patient Selection; D012189:Retrospective Studies; D012507:Sarcoidosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D012871:Skin Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D062606:Tertiary Care Centers; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha
keywords: IL-1 inhibitor; TNF-alpha inhibitor; clinical audit; off-label use