PMID- 29885659 OWN - NLM STAT- MEDLINE DCOM- 20190107 LR - 20240130 IS - 2046-4053 (Electronic) IS - 2046-4053 (Linking) VI - 7 IP - 1 DP - 2018 Jun 9 TI - mTOR-inhibiting pharmacotherapy for the treatment of non-infectious uveitis: a systematic review protocol. PG - 83 LID - 10.1186/s13643-018-0745-2 [doi] LID - 83 AB - BACKGROUND: Non-infectious uveitis represents a sub-type of intraocular inflammation often associated with disorders of immune dysregulation. If untreated, the intraocular inflammation may progress to severe visual impairment and blindness. Current treatment is heavily reliant on systemic corticosteroid, often at doses associated with severe side effects. There is a need for efficacious corticosteroid-sparing immunomodulatory therapy for these patients. Current immunomodulators include various immunosuppressants and biologics but mammalian target of rapamycin (mTOR) inhibitors (such as sirolimus and everolimus) may also be contenders for this role. The systematic review proposed here will evaluate the evidence for the use of sirolimus and everolimus in the context of non-infectious uveitis. METHOD/DESIGN: Standard systematic review methodology will be used to identify, select and extract data from any comparative or non-comparative study of mTOR inhibitors in patients with non-infectious uveitis excluding case reports. Searches of bibliographic databases (MEDLINE, EMBASE, The Cochrane Library and CINAHL) and clinical trials registers will be performed, with no restriction on language or date of publication. Translation of non-English language articles will be undertaken where necessary. The primary outcome of interest will be uveitis activity as measured by vitreous haze. Secondary outcomes will include other pre-specified measures of uveitis activity (such as anterior chamber cells or central macular thickness) best corrected visual acuity, heath-related quality of life, requirement for concurrent treatment and adverse events. Risk of bias assessment will be performed appropriate to each study design. Study selection, data extraction and risk of bias assessment will be undertaken by two reviewers independently. Data will be grouped, tabulated and narratively synthesised. Meta-analysis will be undertaken where appropriate clinical and methodological homogeneity exists. The review will be published according to PRISMA guidance. DISCUSSION: Studies of various designs have investigated the clinical use of mTOR inhibitors for non-infectious uveitis, and a large international randomised controlled trail of sirolimus for non-infectious uveitis is due to report. The findings of this systematic review will help inform ophthalmologists and aid the improvement of treatment protocols for non-infectious uveitis with regard to the use of mTOR inhibitors. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017056390. FAU - Blair, Joshua AU - Blair J AD - Department of Ophthalmology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. AD - Centre for Rare Diseases, Institute of Translational Medicine, Birmingham Health Partners, Birmingham, UK. FAU - Barry, Robert AU - Barry R AD - Department of Ophthalmology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. AD - Centre for Rare Diseases, Institute of Translational Medicine, Birmingham Health Partners, Birmingham, UK. AD - Academic Unit of Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK. FAU - Murray, Philip I AU - Murray PI AD - Academic Unit of Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK. AD - Birmingham and Midland Eye Centre, Sandwell & West Birmingham NHS Trust, Birmingham, UK. FAU - Moore, David J AU - Moore DJ AD - Institute of Applied Health Research, University of Birmingham, Birmingham, UK. FAU - Denniston, Alastair K AU - Denniston AK AUID- ORCID: 0000-0001-7849-0087 AD - Department of Ophthalmology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. a.denniston@bham.ac.uk. AD - Centre for Rare Diseases, Institute of Translational Medicine, Birmingham Health Partners, Birmingham, UK. a.denniston@bham.ac.uk. AD - Academic Unit of Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK. a.denniston@bham.ac.uk. AD - NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK. a.denniston@bham.ac.uk. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20180609 PL - England TA - Syst Rev JT - Systematic reviews JID - 101580575 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Immunosuppressive Agents) RN - 9HW64Q8G6G (Everolimus) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Adrenal Cortex Hormones/*therapeutic use MH - Everolimus/*therapeutic use MH - Humans MH - Immunosuppressive Agents/*therapeutic use MH - Sirolimus/administration & dosage/*therapeutic use MH - TOR Serine-Threonine Kinases/antagonists & inhibitors MH - Treatment Outcome MH - Uveitis/*drug therapy MH - Systematic Reviews as Topic PMC - PMC5994244 OTO - NOTNLM OT - Immunosuppression OT - Mammalian target of rapamycin OT - Systematic review OT - Uveitis OT - mTOR inhibitors COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/06/11 06:00 MHDA- 2019/01/08 06:00 PMCR- 2018/06/09 CRDT- 2018/06/11 06:00 PHST- 2017/08/12 00:00 [received] PHST- 2018/05/16 00:00 [accepted] PHST- 2018/06/11 06:00 [entrez] PHST- 2018/06/11 06:00 [pubmed] PHST- 2019/01/08 06:00 [medline] PHST- 2018/06/09 00:00 [pmc-release] AID - 10.1186/s13643-018-0745-2 [pii] AID - 745 [pii] AID - 10.1186/s13643-018-0745-2 [doi] PST - epublish SO - Syst Rev. 2018 Jun 9;7(1):83. doi: 10.1186/s13643-018-0745-2.