title: Non-anti-TNF biologic modifier drugs in non-infectious refractory chronic uveitis: The current evidence from a systematic review.
abstract: OBJECTIVE
  To examine, separately, in children and adults with autoimmune chronic uveitis (ACU), the evidence regarding the effectiveness and the safety of switching to a non-anti-TNF biologic modifier immunosuppressant treatment (NTT) currently available in clinical practice.
  
  
  METHODS
  A systematic search between January 2000 and April 2014 was conducted using EMBASE, Ovid MEDLINE, Evidence Based Medicine Reviews-ACP Journal Club, Cochrane libraries, and EBM Reviews. Studies investigating the efficacy of NTT as a biologic modifier immunosuppressant medication for ACU, refractory to topical and/or systemic steroid therapy, were eligible for inclusion. The primary outcome measure was the improvement of intraocular inflammation, as defined by the SUN working group criteria. We determined a combined estimate of the proportion of subjects responding to NTT.
  
  
  RESULTS
  We initially identified 526 articles, of which 89 were potentially eligible. From the selection process, a total of 10 retrospective chart reviews and a randomized single-blind controlled study, providing a total of 12 children and 34 adults, were deemed eligible: 3 articles looked at rituximab, 3 at abatacept, 3 at tocilizumab, and the remaining 1 at alemtuzumab and the other at anakinra. Before the NTT treatment, all the eligible subjects received several combinations of one or more DMARDs and at least one anti-TNF strategy. With the exclusion of 7 adults enrolled in the RCT, 8 of 12 children and 18 of 27 adults responded to NTT treatment: 0.66 was the combined estimate of the proportion of subjects improving on NTT treatment in children (95% CI: 0.46-0.99) and in adults (95% CI: 0.49-0.84). Further statistical comparison between different NTT strategies was not possible due to the small sample size.
  
  
  CONCLUSIONS
  Although randomized controlled trials are needed, the available evidence suggests the clinical use of a NTT strategy in selected categories of ACU, refractory to previous course of immunosuppressive treatment, DMARDs, as well as anti-TNFα, in adults as well as children.
authors.affiliation: Rheumatology Unit-Department of Paediatrics, University of Florence, viale Pieraccini #24, Firenze 50139, Italy. Electronic address: gabriele.simonini@unifi.it.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Simonini
authors.affiliation: Rheumatology Unit-Department of Paediatrics, University of Florence, viale Pieraccini #24, Firenze 50139, Italy.
authors.forename: Rolando
authors.initials: R
authors.lastname: Cimaz
authors.affiliation: Musculoskeletal Research Programme-Epidemiology Group, Institute of Applied Health Sciences, University of Aberdeen, UK.
authors.forename: Gareth T
authors.initials: GT
authors.lastname: Jones
authors.affiliation: Musculoskeletal Research Programme-Epidemiology Group, Institute of Applied Health Sciences, University of Aberdeen, UK.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Macfarlane
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001688:Biological Products / Q000627:therapeutic use*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D000069283:Rituximab / Q000627:therapeutic use; D016896:Treatment Outcome; D014605:Uveitis / Q000188:drug therapy*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D053590:Interleukin 1 Receptor Antagonist Protein; D000074323:Alemtuzumab; D000069283:Rituximab; D000069594:Abatacept; C502936:tocilizumab
keywords: Abatacept; Alemtuzumab; Anakinra; Autoimmune chronic uveitis; Rituximab; Tocilizumab