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Efficacy and safety of microbiota- targeted therapeutics in autoimmune and inflammatory rheumatic diseases: protocol for a systematic review and meta-analysis of randomised controlled trials Maja Skov Kragsnaes , 1,2 Benoit Thomas P Gilbert , 3 Bjørk Khaliqi Sofíudóttir , 2,4 Christopher Michael Rooney, 5,6 Sebrina Maj-Britt Hansen, 7 Daniele Mauro, 8 Benjamin H Mullish , 9,10 Anne-Sophie Bergot, 11 Kulveer Singh Mankia, 12 Niti Goel, 13 Gunnstein Bakland, 14 Peter Holger Johnsen, 15 Jesus Miguens Blanco, 9 Simone Li , 16 Emilie Dumas, 17,18 Philip Rask Lage-Hansen , 19 Carlijn Wagenaar, 20 Ghaith Bakdash, 21 Mat Robinson, 21 Karsten Kristiansen, 22 Julian R Marchesi, 9 Georg Schett , 23,24 Mario M Zaiss, 23,24 Mine Orlu, 25 Dirkjan van Schaadenburg, 20 Jose U Scher, 26 Dennis McGonagle , 27 Dirk Elewaut , 17,18 Maxime Breban, 28,29 Peter Tugwell, 30 Axel Finckh , 3 Francesco Ciccia, 8 Martin A Kriegel, 31,32,33 Claire Daien, 34 Torkell Ellingsen , 1,2 Robin Christensen , 2,35 EULAR Study Group MICMUC
To cite: Kragsnaes MS, Gilbert BTP, Sofíudóttir BK, et al . Efficacy and safety of microbiota-targeted therapeutics in autoimmune and inflammatory rheumatic
ABSTRACT Introduction An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research. Methods and analysis This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals,
STRENGTHS AND LIMITATIONS OF THIS STUDY ⇒ This protocol follows Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols guidelines, ensuring a robust and standardised methodology. ⇒ A predefined comprehensive search strategy across three databases combined with a search at ClinicalTrials.gov, as recommended by the Cochrane Musculoskeletal Group, and the WHO International Clinical Trial Registry Platform por- tal will be used to identify eligible trials. ⇒ Due to an international author group, no language restrictions will be imposed on the selection of studies. ⇒ Data on safety, primary trial endpoints and sev- en predefined efficacy outcomes reflecting the OMERACT core domains across chronic auto- immune and inflammatory rheumatic diseases will be systematically collected and presented separately. ⇒ We will use the Grading of Recommendations Assessment, Development and Evaluation sys- tem to summarise the certainty of evidence, which will enhance the transparency and reli- ability of our conclusions.
diseases: protocol for a systematic review and
meta-analysis of randomised controlled trials. BMJ Open 2025; 15 :e101593. doi:10.1136/
bmjopen-2025-101593 ► Prepublication history
and additional supplemental material for this paper are available online. To view these files, please visit the journal online (https://doi.org/10.1136/ bmjopen-2025-101593). Received 03 March 2025 Accepted 21 November 2025 © Author(s) (or their employer(s)) 2025. Re-use For numbered affiliations see end of article. permitted under CC BY. Published by BMJ Group. Correspondence to Dr Maja Skov Kragsnaes; d 063631@dadlnet.d k
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Kragsnaes MS, et al . BMJ Open 2025; 15 :e101593. doi:10.1136/bmjopen-2025-101593
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