Annals of the Rheumatic Diseases最新文献

{"title":"New IgG and IgA autoantibody specificities against DNA-binding and RNA-binding proteins discriminate systemic lupus erythematosus from health and non-lupus autoimmunity-could anti-LIN28A enhance precision in diagnostics?","authors":"Ioannis Parodis, Denis Lagutkin, Julius Lindblom, Helena Idborg, Lorenzo Beretta, Maria Orietta Borghi, Janique M Peyper, Guillermo Barturen, Per-Johan Jakobsson, Marta E Alarcón-Riquelme, Natalia Sherina, Dionysis Nikolopoulos","doi":"10.1016/j.ard.2025.04.003","DOIUrl":"10.1016/j.ard.2025.04.003","url":null,"abstract":"<p><strong>Objectives: </strong>In response to the urgent unmet needs of heterogeneity, unpredictability, and diagnostic delay in systemic lupus erythematosus (SLE), we aimed to identify and validate new immunoglobulin (Ig)G and IgA autoantibody specificities.</p><p><strong>Methods: </strong>Using a KoRectly EXpressed technology-based microarrays (i-Ome Discovery; Sengenics), we screened for circulating IgG and IgA autoantibodies against 1609 proteins in 2 independent cohorts (discovery: NTC02890121; validation: NCT02890134) comprising patients with SLE (n = 199 and n = 30), primary Sjögren's disease (n = 115 and n = 31), and systemic sclerosis (n = 115 and n = 24), and healthy controls (HCs; n = 111 and n = 84), respectively.</p><p><strong>Results: </strong>We identified and validated 5 IgG (anti-Lin-28 homolog A [LIN28A], anti-HNRNPA2B1, anti-HMG20B, anti-HMGB2, and anti-alpha-globin transcription factor CP2 [TFCP2]) and 4 IgA (anti-LIN28A, anti-HMG20B, anti-SUB1, and anti-TFCP2) autoantibodies that demonstrated high specificity for SLE (0.91-0.94), along with consistent and robust positivity (0.22-0.69) in differentially abundant autoantibody (daAAb) analysis between SLE and comparator groups. IgG and IgA anti-LIN28A levels varied over a 14-month follow-up in the validation cohort of newly diagnosed patients with SLE and exhibited metrics that outperformed those of traditional autoantibody markers such as anti-double-stranded DNA. Clustering of patients with SLE based on autoantibody positivity (levels above the HC median plus 2 IQRs in the discovery cohort) status revealed 1 subgroup demonstrating seroreactivity against multiple antigens, 3 exhibiting varying reactivity, and 1 showing no reactivity. In pathway analysis, daAAb targets pointed to DNA-binding and RNA-binding and transcription functions.</p><p><strong>Conclusions: </strong>Novel autoantibodies validated in this study may enhance diagnostics and molecular characterisation in SLE. The prominent IgA seroreactivity implicates important roles of mucosal tissues in SLE autoimmunity, warranting further investigation.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1180-1194"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipidomics unravels lipid changes in osteoarthritis articular cartilage.","authors":"Qiongfei Zhou, Mohan Ghorasaini, Frederique M F Cornelis, Reem Assi, Astrid de Roover, Martin Giera, Silvia Monteagudo, Rik J Lories","doi":"10.1016/j.ard.2025.01.009","DOIUrl":"10.1016/j.ard.2025.01.009","url":null,"abstract":"<p><strong>Objectives: </strong>Osteoarthritis (OA) is linked to disrupted lipid metabolism. We aimed to profile the lipid composition of human articular cartilage, investigate OA-associated lipidome changes, and explore biological effects.</p><p><strong>Methods: </strong>Lipidomic profiling and computational analyses were performed on human articular chondrocytes (hACs) from non-OA (n = 13) and OA (n = 14) hips. Lipid changes were confirmed in the destabilisation of the medial meniscus (DMM) mouse model. The effect of specific lipids was evaluated by in vitro supplementation and gene silencing.</p><p><strong>Results: </strong>We identified 573 lipid species covering 11 lipid classes in hACs. OA and non-OA hACs showed distinct lipid profiles. Most ceramides and dihydroceramides were increased, while cholesteryl esters, diacylglycerols, triacylglycerols, sphingomyelins, hexosylceramides, and lactosylceramides were predominantly decreased in OA chondrocytes. Most upregulated lipids in OA contained C18:1, C20:4, or C22:4 side chains. Many downregulated lipids contained C18:2 or odd-chain C17:0. Lipid profiling of articular cartilage from the DMM mouse model paralleled changes in OA hACs, including odd-chain C17:0 reduction. Further analysis showed that deficiency in enzyme 2-hydroxyacyl-CoA lyase 1 (HACL1), responsible for odd-chain fatty acid synthesis, leads to accumulation of 2-hydroxy C18:0, precursor of C17:0, which results in a shift in hACs from an anabolic to a catabolic state.</p><p><strong>Conclusions: </strong>Our study maps the hAC lipid composition and highlights changes in lipid profiles associated with OA. Dysregulation of certain lipids, especially odd-chain fatty acids, linked to a deficiency in the enzyme HACL1, leads to pathological changes. This understanding opens potential avenues for therapies aimed at targeting lipid imbalances to slow down or treat OA.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1264-1276"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to: Correspondence on '2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria' by Yeng et al.","authors":"Medha Barbhaiya, Stephane Zuily, Alison Hendry, Florian Manneville, Francis Guillemin, Karen Costenbader, Doruk Erkan","doi":"10.1016/j.ard.2025.03.004","DOIUrl":"10.1016/j.ard.2025.03.004","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"e35"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correspondence on 'Methotrexate continuation increases fracture risk in patients who sustained lower limb insufficiency fractures' by Hauser et al.","authors":"Yijun Dai, Shuo Feng, Chuanhui Xu","doi":"10.1016/j.ard.2025.03.010","DOIUrl":"https://doi.org/10.1016/j.ard.2025.03.010","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 7","pages":"e29-e30"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimitochondrial antibodies in systemic sclerosis target enteric neurons and are associated with GI dysmotility.","authors":"Zsuzsanna H McMahan, Srinivas N Puttapaka, Livia Casciola-Rosen, Timothy Kaniecki, Laura Gutierrez-Alamillo, Su Hong Ming, Philippa Seika, Subhash Kulkarni","doi":"10.1016/j.ard.2025.06.2119","DOIUrl":"10.1016/j.ard.2025.06.2119","url":null,"abstract":"<p><strong>Objectives: </strong>Most patients with systemic sclerosis (SSc) experience gastrointestinal (GI) dysmotility. The enteric nervous system (ENS) regulates GI motility, and its dysfunction causes dysmotility. A subset of SSc patients harbour antimitochondrial M2 autoantibodies (AM₂A). Here, we investigate whether M2 is expressed by specific ENS cells, and if AM₂A are associated with GI dysmotility in SSc patients.</p><p><strong>Methods: </strong>Sera from 154 well-characterised patients with SSc were screened for AM₂A by enzyme-linked immunosorbent assay. Clinical features and GI transit data were compared between AM₂A-positive and AM₂A-negative patients. Hepatocellular carcinoma cell line 2 (HepG2) cells were cultured with these sera and costained with AM₂A.</p><p><strong>Results: </strong>Nineteen of 147 patients (12.9%) were AM₂A-positive. AM₂A positivity was significantly associated with slower transit in the oesophagus (β -14.4, 95%CI, -26.2, -2.6) and stomach (β -7.9, 95% CI, -14.1, -1.6). Immunostaining demonstrated pan-mitochondrial antigens TOM-20 and M2 enrichment in human ENS neurons, specifically in mesoderm-derived enteric neurons (MENS). Autoantibodies in SSc sera penetrated live adult murine MENs and HepG2 cells when adult murine longitudinal muscle containing myenteric plexus tissue and HepG2 cells were cultured in the presence of SSc sera. Upon penetrating live cells, AM₂A localised to mitochondria, and immunoprecipitation demonstrated binding to the M2 antigen. Seahorse assays show that penetration of HepG2 cells with SSc-AM₂A altered cellular respiration suggesting that penetrating AM₂A is pathogenic.</p><p><strong>Conclusions: </strong>AM₂A in SSc patients are associated with slower GI transit. SSc autoantibodies penetrate live cells in vitro, and SSc-AM2A penetrates live cells to target the mitochondrial M2 antigen and cause functional deficits. Because a subset of enteric neurons (MENs) is enriched in mitochondria, which are similarly penetrated by SSc-AM₂A in vitro, the presence of GI dysmotility in SSc patients harbouring AM₂A suggests that SSc-AM₂A may penetrate MENs in vivo, driving ENS and GI dysfunction. Further studies are warranted to test how AM₂A alter ENS functions in vivo to contribute to GI dysmotility in SSc.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease Trajectories and Glucocorticoid Exposure in VEXAS Syndrome Treated with Cytokine-Directed Therapies.","authors":"Benjamin A Turturice, Alice Fike, Bhavisha A Patel, Emma M Groarke, Fernanda Gutierrez-Rodriguez, Karyssa Stonick, Hannah Berrett, Shanni Liu, Ivana Darden, Kaitlin A Quinn, Neal S Young, Peter C Grayson","doi":"10.1016/j.ard.2025.05.021","DOIUrl":"https://doi.org/10.1016/j.ard.2025.05.021","url":null,"abstract":"<p><strong>Objectives: </strong>To establish the long-term impact of cytokine-directed therapies on glucocorticoid use and clinical outcomes in Vacuoles, E1-enzyme, X-linked, Autoinflammatory, Somatic (VEXAS).</p><p><strong>Methods: </strong>Patients with VEXAS were prospectively followed for events of transfusion dependence, haematopoietic stem cell transplantation or death. Laboratory results, glucocorticoid exposure and clinical measures were retrospectively assessed in relationship to treatment initiation with interleukin-6-directed therapies (anti-IL6R) or Janus kinase inhibitors (JAKi). Patients were stratified by UBA1 variants and presence of typical clonal haematopoiesis with variant allele fraction ≥ 10% (CH^V^AF^≥^10%).</p><p><strong>Results: </strong>In 71 VEXAS patients (81.7% with anti-IL6R or JAKi exposure), event-free survival differed by genotype and presence of concomitant CH^V^AF^≥^10%: p.M41V (HR [95% confidence interval (CI)]: 5.7 [1.5-20.4]) or p.M41L/T with CH^V^AF^≥^10% (hazard ratio [HR]: 5.7 [1.6-20.8]) compared to p.M41L. No association between event rates and exposure to anti-IL6R or JAKi was observed. The p.M41V genotype had the highest risk of anaemia, elevated C-reactive protein (CRP) levels, and monocytopenia. Over a median follow-up of 4.8 (interquartile range [IQR] 3.0, 8.1) years, the patients' mean glucocorticoid dose was >15 mg/day prednisone regardless of variant or disease duration. At prospective visits, clinical remission on ≤10 mg/day prednisone was observed in only 2.7% of visits. Treatment with anti-IL6R or JAKi showed no clinically meaningful reduction (<5 mg/day difference) in steroid exposure at 1 year post-treatment. No attenuation in the progression of anaemia was observed in response to anti-IL6R and JAKi.</p><p><strong>Conclusions: </strong>Cytokine-directed therapies alone do not alter the risk of haematologic disease progression or significantly reduce glucocorticoid exposure in VEXAS. These data provide benchmarks for future interventional studies.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vasculopathy, embolism, xerostomia, arthritis, and stomachache.","authors":"Weijin Zhang, Songhao Cai, Shaoyu Zheng, Shijian Hu, Kedi Zheng, Jianqun Lin, Manna Chen, Guangzhou Du, Marco Matucci-Cerinic, Daniel E Furst, Yukai Wang","doi":"10.1016/j.ard.2025.06.003","DOIUrl":"https://doi.org/10.1016/j.ard.2025.06.003","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix stiffness regulates profibrotic fibroblast differentiation and fibrotic niche activation in systemic sclerosis.","authors":"Ludwig Ueberall, Hashem Mohammadian, Richard Demmler, Yuko Ariza, Philipp Tripal, Charles Gwellem Anchang, Stefanie Weber, Mario Raphael Angeli, Maria Gabriella Raimondo, Jiyang Chang, Kaiyue Huang, Jörg H W Distler, Oliver Distler, Simon Rauber, Georg Schett, Andreas Ramming, Alina Mihaela Ramming","doi":"10.1016/j.ard.2025.05.016","DOIUrl":"https://doi.org/10.1016/j.ard.2025.05.016","url":null,"abstract":"<p><strong>Objectives: </strong>Fibrosis progression in systemic sclerosis (SSc) has been attributed to matrix stiffness. Despite extensive research on fibroblast heterogeneity and subset imbalances in fibrotic disorders, the interplay between biomechanical cues and fibroblast dynamics remains largely unexplored. Here, we investigate how matrix stiffness alters fibroblast transcriptional state and influences lineage specification in fibrotic skin.</p><p><strong>Methods: </strong>We employed a collagen I-based 3-dimensional culture system to expose fibroblasts to varying levels of matrix stiffness, followed by RNA sequencing to identify stiffness-responsive gene expression signature. We integrated single-cell RNA sequencing data from SSc and healthy skin samples to identify fibroblast subsets associated with this signature. Spatial transcriptomic analyses were performed to localise these fibroblasts and their associations with the fibrotic niche.</p><p><strong>Results: </strong>Fibroblasts subjected to increased matrix stiffness exhibited a distinct transcriptional signature, amplified in SSc patients and enriched in PI16⁺ progenitor-like cells within the SFRP2⁺ fibrotic compartment. Further analysis indicated that PI16⁺ fibroblasts are predisposed to SFRP2⁺COMP⁺ PU.1⁺ myofibroblasts differentiation, whereas blocking mechanotransduction by focal adhesion kinase inhibition disrupts this process, suggesting that matrix stiffness is a key driver of this lineage transition. Spatial mapping revealed colocalisation of the PI16⁺ and COMP⁺ subsets in extracellular matrix-dense regions, highlighting the functional relevance of this relationship in fibrotic progression.</p><p><strong>Conclusions: </strong>Our findings suggest that increased matrix stiffness promotes fibroblast precursor differentiation into SFRP2⁺ COMP⁺ PU.1⁺ myofibroblasts, thereby sustaining the vicious cycle of persistent fibrosis in absence of inflammatory triggers. These insights reveal new aspects of fibrosis pathogenesis and highlight biomechanical signals as therapeutic targets in SSc.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative risk of incident malignancies in rheumatoid arthritis patients treated with Janus kinase inhibitors or bDMARDs: observational data from the German RABBIT register.","authors":"Martin Schaefer, Alina Purschke, Vera Zietemann, Tatjana Rudi, Yvette Meissner, Adrian Richter, Sylvia Berger, Karin Rockwitz, Klaus Krüger, Karl Matthias Schneider, Anne C Regierer, Anja Strangfeld","doi":"10.1016/j.ard.2025.05.014","DOIUrl":"https://doi.org/10.1016/j.ard.2025.05.014","url":null,"abstract":"<p><strong>Objectives: </strong>To estimate the effects of Janus kinase inhibitors (JAKis) vs biologic disease-modifying antirheumatic drugs (bDMARDs) on the risk of incident malignancies (excluding nonmelanoma skin cancer) in patients and patient subgroups with rheumatoid arthritis.</p><p><strong>Methods: </strong>Episodes of disease-modifying antirheumatic drug (DMARD) treatment initiated between January 2017 and December 2020 and followed up to June 2024 in RABBIT, the German register for the long-term observation of therapy with biologics and targeted disease-modifying antirheumatic drugs in adult patients with rheumatoid arthritis, were analysed. Incidence rates (IRs) per 1000 patient-years with 95% CIs were calculated, and incident malignancy risk was estimated as hazard ratios (HRs) by inverse probability weighted adjusted Cox models.</p><p><strong>Results: </strong>Among 2285 JAKi and 4259 bDMARD treatment episodes, 88 and 135 malignancies occurred, respectively. JAKi treatments were dominated by baricitinib and tofacitinib, while most bDMARD treatments comprised tumour necrosis factor inhibitors. IRs were 11.6 (95% CI: 9.3, 14.3) in JAKi- and 8.9 (95% CI: 7.4, 10.5) in bDMARD-treated groups. The adjusted HR comparing JAKis with bDMARDs was 1.40 (95% CI: 1.09, 1.80). An increase in the malignancy risk for JAKi vs bDMARD treatment could only be observed in treatment episodes lasting longer than 16 months. The risk appeared higher in some subgroups of patients, including those who started treatment aged ≥60 years, patients with ≥3 prior conventional synthetic DMARD treatments, and patients with high disease activity.</p><p><strong>Conclusions: </strong>In this German observational cohort study, an overall small increase in malignancy risk for JAKi vs bDMARD treatment was observed, with more pronounced risks in some subgroups of patients. The observed risk should be carefully counterbalanced to the known malignancy risk associated with insufficient disease control.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of treatments in familial Mediterranean fever and its complications: a systematic review informing the EULAR/PReS recommendations for familial Mediterranean fever.","authors":"Erdal Sag, Teresa Otón, Loreto Carmona, Seza Ozen","doi":"10.1016/j.ard.2025.05.020","DOIUrl":"https://doi.org/10.1016/j.ard.2025.05.020","url":null,"abstract":"<p><strong>Objectives: </strong>To analyse the efficacy and safety of (1) the biological agents and tofacitinib in the treatment of familial Mediterranean fever (FMF); (2) the biological agents and tofacitinib in FMF patients with complications such as amyloidosis; and (3) the colchicine preparations and dosing strategies to serve as evidence supporting the updated European Alliance of Associations for Rheumatology (EULAR) recommendations.</p><p><strong>Methods: </strong>This was a systematic review (SR) of studies testing pharmacological treatments in FMF patients, including targets, dosing, tapering, and uses in AA amyloidosis. MEDLINE, Embase, and the Cochrane Library were searched, focusing on studies published after October 1, 2014. The Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale were used to assess the risk of bias in the included randomised controlled trials (RCTs) and observational studies, respectively. Due to excess heterogeneity, results were synthesised qualitatively.</p><p><strong>Results: </strong>This SR included 42 studies for efficacy and safety (n = 1798 patients), 13 for tapering, and 31 for amyloidosis. Based on 6 RCTs of interleukin (IL)-1 blockers and observational studies, these biologicals seem to be effective in decreasing the number of attacks and acute-phase reactants and improving disease activity scores and patient-reported outcomes. They also seem relatively safe. An RCT showed the equivalence of once-daily vs twice-daily doses of colchicine. The evidence of AA amyloidosis was entirely observational but reassuring for a deadly complication.</p><p><strong>Conclusions: </strong>Biological agents, particularly IL-1 inhibitors, are effective and relatively safe options for FMF patients who do not respond to colchicine. These treatments may be promising alternatives for managing symptoms and preventing comorbidities in both paediatric and adult populations.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}