Open access
Objective The main objective of this protocol is to outline the methods for conducting a systematic review and meta- analysis of randomised controlled trials (RCTs) evalu- ating the effectiveness and safety of therapies targeting the intestinal microbiota and/or gut barrier function in patients with AIRDs. Comparators will include inactive controls, established disease-modifying anti-rheumatic drugs (DMARDs) or other microbiota-targeted therapies. The secondary objective of the planned study is to assess the quality of trials fulfilling the eligibility criteria for study inclusion using the Cochrane Risk of Bias tool V.2. 55
Box 1 List of included autoimmune and inflammatory rheumatic diseases (AIRDs).
AIRDs Rheumatoid arthritis Juvenile idiopathic arthritis Axial spondyloarthritis Psoriatic arthritis Enteropathic arthritis Reactive arthritis
Undifferentiated spondyloarthritis Systemic lupus erythematosus Antiphospholipid syndrome
Adult Still’s disease Systemic sclerosis Sjögren’s disease Mixed connective tissue disease Giant cell arteritis Polymyalgia rheumatica Takayasu arteritis Polyarteritis nodosa ANCA-associated vasculitis Microscopic polyangiitis Granulomatosis with polyangiitis Eosinophilic granulomatosis with polyangiitis Behçet’s disease Anti-GBM disease Cryoglobulinaemic syndrome Polymyositis Dermatomyositis Clinical amyotrophic dermatomyositis
METHODS AND ANALYSIS Methodological guidelines
The handbook guidance published by the Cochrane Collaboration (V.6, 2019) 56 57 and the reporting guide- lines for protocols of systematic reviews and meta-analyses (PRISMA-P) endorsed by the EQUATOR network have directed the planning and reporting of this protocol. 58 In accordance with the guideline and prior to the conduct of the search and review process, the protocol was registered with the International Prospective Register of System- atic Reviews (registration date: 15 February 2025). The reporting of the results will follow the guidelines from EQUATOR on systematic reviews (PRISMA statement). 59 Criteria for selecting studies for this review Studies will be selected according to the criteria defined below.
Inclusion body myositis Antisynthetase syndrome Eosinophilic myositis Eosinophilic fasciitis Relapsing polychondritis Sarcoidosis Periodic fever syndrome Familial Mediterranean fever
Study designs Only RCTs will be considered for eligibility.
Participants Eligible studies must include individuals diagnosed with one of the AIRDs listed in Box 1. To ensure consistency with rheumatology research practice while avoiding unnecessary exclusion of earlier trials, we will accept diag- noses based on recognised diagnostic criteria or estab- lished classification criteria available at the time the study was conducted. If no classification criteria were available for a given condition at the time, we will accept a clinical diagnosis, reflecting routine practice in early rheuma- tology intervention. No restrictions will be applied on age or sex/gender. Interventions The therapies targeting the intestinal microbiota and/or gut barrier function being evaluated in this review encom- pass interventions administered to the gastrointestinal tract with the intention to treat AIRDs through modifica- tion(s) of the intestinal milieu (please see the definition of the selected therapies below). No restrictions are applied on dosage, frequency, duration of treatment or route of administration. The microbiota-targeted interventions being evaluated are as follows:
TNF-receptor associated periodic syndrome Cryopyrin associated periodic syndromes
1. Probiotics defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (eg, bacteria of the genera Lactobacillus , Bifidobacterium , Enterococcus or the species Escherichia coli ). 60 2. Synbiotics are defined as a combination of prebiotics and probiotics. 3. Postbiotics are defined as a preparation of inanimate microorganisms and/or their components that con- fers a health benefit on the host (ie, intact non-viable microbes or cell fragments, with or without metabo- lites such as heat-killed Akkermansia muciniphila ). 61 4. FMT products, encompassing minimally manipulat- ed communities of intestinal micro-organisms from healthy individuals (donors). 62 63 5. Live biotherapeutic products registered as medicinal products (pharmabiotics), defined as (1) containing live organisms, such as bacteria or bacterial spores; (2)
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Kragsnaes MS, et al . BMJ Open 2025; 15 :e101593. doi:10.1136/bmjopen-2025-101593
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