Annals of the Rheumatic Diseases最新文献

{"title":"Three years is the minimal effective duration of sustained clinical remission which prevents impaired kidney function and damage accrual in lupus nephritis.","authors":"Mariele Gatto, Giulia Frontini, Claudia Furlan, Marta Calatroni, Claudio Cruciani, Francesco Reggiani, Elisa Bellis, Luca Iaccarino, Renato Alberto Sinico, Gabriella Moroni, Andrea Doria","doi":"10.1016/j.ard.2025.02.004","DOIUrl":"https://doi.org/10.1016/j.ard.2025.02.004","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the minimum effective duration of remission preventing damage accrual (Systemic Lupus International Collaborating Clinics damage index [SDI]) and impaired kidney function (IKF: estimated glomerular filtration rate of <60 mL/min/1.73 m² for at least 3 months) in active lupus nephritis (LN).</p><p><strong>Methods: </strong>Patients with biopsy-proven LN followed up at least twice yearly were enrolled; clinical variables were collected regularly. Sustained clinical remission (sCR) was defined as estimated glomerular filtration rate of >60 mL/min/1.73 m², proteinuria of <0.5 g/24 h and clinical systemic lupus erythematosus disease activity index of 0 for at least 1 year. Log-linear regression and a time-dependent Cox proportional hazard model were used to assess the minimum duration of sCR capable of preventing SDI increase and IKF development.</p><p><strong>Results: </strong>In total, 293 patients with LN were included (median follow-up: 15.7 [10.4-22.9] years) of whom 84.3% achieved sCR lasting 8.7 (5.4-13.1) years. At last observation, the increase in SDI was higher in patients who never achieved sCR (median: 2 [1-2.5] vs 1 [0-1.5]; P < .001). A minimum duration of 3 years of sCR prevented SDI increase (% change = -41.1%; P = .003). The analysis on IKF involved only patients with the longest follow-up; 224 patients had ≥10 years of observation. Among them, 50 (22.3%) developed IKF. A minimum duration of 3 years of sCR prevented IKF (hazard ratio = 0.10; P < .001). IKF-free survival rate at 10, 20, and 25 years was 87%, 68%, and 40% for patients who never achieved sCR and 99%, 96%, and 91% for patients with at least 3 years of sCR, respectively (P < .001).</p><p><strong>Conclusions: </strong>Three years is the minimum duration of sCR protecting against development of IKF and damage accrual in patients with LN.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536541","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":"Safety of colchicine on fertility, pregnancy, and lactation: a systematic review and meta-analysis informing the EULAR/PReS recommendations for familial Mediterranean fever.","authors":"Teresa Otón, Erdal Sağ, Loreto Carmona, Seza Ozen","doi":"10.1016/j.ard.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.ard.2025.02.005","url":null,"abstract":"<p><strong>Objectives: </strong>To summarise the evidence of colchicine's effects on fertility, pregnancy, and lactation in the treatment of patients with familial Mediterranean fever (FMF).</p><p><strong>Methods: </strong>Two reviewers and a methodologist conducted the systematic review. Together with an expert in FMF, they established the protocol and the PICOt questions. Medline via PubMed, Embase, and the Cochrane Library were searched from inception until August 23, 2023. All clinical trials, cohort studies, or case series focused on the safety of colchicine in FMF, concerning reproductive issues or breastfeeding, and involving at least 5 patients were eligible. The risk of bias in the studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis was planned for at least 2 homogeneous studies with fixed-effect models using the Mantel-Haenszel method to obtain the pooled risk ratio (RR) and 95% CI.</p><p><strong>Results: </strong>Twenty-five studies were included overall of moderate to low quality. The RR of miscarriage or foetal loss with colchicine in FMF was 0.87 (95% CI, 0.67-1.12), showing a heterogeneity of 31%. The percentage of birth defects in the exposed group ranged from 0.6% to 4.0%, not very different, comparable to the rates of women with FMF without exposure to colchicine. Regarding fertility, there were no apparent differences between colchicine-exposed and nonexposed groups, neither among women nor men (sperm assessment). Only 1 study reported breastfeeding data, showing no growth differences among exposed and nonexposed babies.</p><p><strong>Conclusions: </strong>Colchicine appears to have a good risk-benefit profile regarding reproductive safety. Ideally, higher-quality studies should be performed, especially regarding male fertility.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536529","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":"Responsiveness of systemic lupus erythematosus subjects to iberdomide based on molecular endotypes.","authors":"Prathyusha Bachali, Andrea Daamen, Shimon Korish, Yanhua Hu, Peter Schafer, Amrie Grammer, Peter E Lipsky","doi":"10.1016/j.ard.2025.01.044","DOIUrl":"https://doi.org/10.1016/j.ard.2025.01.044","url":null,"abstract":"<p><strong>Objectives: </strong>Iberdomide is a cereblon E3-ligase modulator that promotes proteasomal degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) and was shown to be efficacious among subjects with generalised systemic lupus erythematosus (SLE). This study sought to identify baseline gene expression profiles of SLE subjects responsive to iberdomide and analyse the impact of this agent on gene expression.</p><p><strong>Methods: </strong>Whole blood samples obtained from 276 female SLE subjects in the phase 2b iberdomide trial (NCT03161483) were assessed by RNA sequencing followed by gene set variation analysis (GSVA) using 32 informative gene modules. Unsupervised K-means clustering categorised subjects according to molecular endotypes at baseline. Each endotype was compared for treatment related gene expression changes.</p><p><strong>Results: </strong>K-means clustering of GSVA scores from whole blood yielded 5 patient subsets (endotypes A-E) with increases in molecular abnormalities indicative of enhanced immune activity. Significant clinical responses to iberdomide, determined using the SLE Responder Index 4, were confined to endotypes C and E. The most important treatment related gene modules in responders in endotype E were Treg cells, B cells, and interferon, whereas unfolded proteins, oxidative phosphorylation and anergic/activated T cells were associated with responsiveness in endotype C.</p><p><strong>Conclusions: </strong>Molecular profiles of SLE subjects identified pharmacodynamic effects of iberdomide that occurred in all endotypes as well as changes in specific gene modules altered in endotypes associated with a significant clinical response. Thus, gene expression-based molecular profiling may be useful to enrich clinical trials for treatment-responsive subjects and also monitor the pharmacodynamic impact of therapy.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530935","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":"Teclistamab in relapsed systemic sclerosis after autologous haematopoietic stem cell transplantation.","authors":"Elise Siegert, Robert Biesen, Maria Dzamukova, Christian Furth, Meike Probst, Felix Doellinger, Thula Walter-Rittel, Anja Fleischmann, Artur Wilhelm, Anne Elisabeth Beenken, Edgar Wiebe, Ann-Christin Pecher, Jörg Henes, Stefan Florian, David Simon, Arnd Kleyer, Gerd-Rüdiger Burmester, Ulrich Keller, Jan Krönke, Gerhard Krönke, Tobias Alexander","doi":"10.1016/j.ard.2025.01.043","DOIUrl":"https://doi.org/10.1016/j.ard.2025.01.043","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498081","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":"A coding single nucleotide polymorphism in the interleukin-6 receptor enhances IL-6 signalling in CD4 T cells and predicts treatment response to tocilizumab in giant cell arteritis.","authors":"Robert Zorc, Christopher Redmond, McKella Sylvester, Mary Maclean, Luciana Yamamoto de Almeida, Kaitlin A Quinn, Alessandro Tomelleri, Corrado Campochiaro, Lorenzo Dagna, Fernanda Gutierrez-Rodrigues, Kristina V Wells, Cameron Rankin, Sabrina Helmold Hait, Chloe Palmer, Robert Corty, Alexander Bick, Kathi Lambert, Jane H Buckner, John J O'Shea, Jin Kyun Park, Massimo Gadina, Peter C Grayson","doi":"10.1016/j.ard.2025.01.049","DOIUrl":"https://doi.org/10.1016/j.ard.2025.01.049","url":null,"abstract":"<p><strong>Objectives: </strong>The study objective was to determine if a common single nucleotide polymorphism in the interleukin 6 (IL-6) receptor (rs2228145, p.Asp358Ala) predicted treatment response to tocilizumab in giant cell arteritis (GCA).</p><p><strong>Methods: </strong>Genetic sequencing of the rs2228145 locus was performed in 2 independent cohorts of patients with GCA. Peripheral blood mononuclear cells (PBMCs) from patients and controls were evaluated for expression of the interleukin 6 receptor (IL-6R) and its coreceptor, gp130, using flow cytometry. The same PBMCs were stimulated with IL-6 and evaluated for downstream targets of IL-6: STAT3 phosphorylation (pSTAT3) and IL-17A expression.</p><p><strong>Results: </strong>In total, 100 patients with GCA were included (derivation cohort n = 58; validation cohort n = 42). The rs2228145 variant predicted tocilizumab response in each cohort. In the derivation cohort, a gene dose-dependent response was observed with a 36% response rate in the homozygous patients and 95% response rate in patients without the variant (P = .003). In the validation cohort, tocilizumab response rates were 50% for homozygotes and 85% for patients without the variant (P = .04). pSTAT3 levels were significantly increased in response to IL-6 stimulation in a gene dose-dependent manner in CD4 T cells from patients with GCA but not controls. CD4 T cells from patients with GCA had significantly higher membrane expression of gp130 than healthy controls, and response to IL-6 correlated with gp130 expression. IL-17 producing CD4 T cells were increased in a gene dose-dependent response to IL-6 (P < .01).</p><p><strong>Conclusions: </strong>The rs2228145 variant is associated with decreased treatment response to tocilizumab and worse outcomes in GCA by enhancing CD4 T cell response to IL-6.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498077","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":"Increased healthcare utilisation in the 5 years preceding systemic lupus erythematosus diagnosis: a Danish nationwide cohort study.","authors":"Sofie Geday, Anders Prior, Henrik Schou Pedersen, Annette de Thurah, Esben Næser, Anne Troldborg","doi":"10.1016/j.ard.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.ard.2025.02.001","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to analyse healthcare utilisation patterns in the 5 years preceding a diagnosis of systemic lupus erythematosus (SLE) in Denmark compared to matched healthy individuals. Understanding these patterns could support earlier diagnosis and reduce diagnostic delay.</p><p><strong>Methods: </strong>A nationwide, registry-based cohort study was conducted using data from the Danish national healthcare registries between 2006 and 2021. Healthcare utilisation, including general practitioner (GP) visits, specialist consultations, prescriptions, blood tests, diagnostic imaging, and hospital admissions, was examined. Incidence rate ratios were calculated using negative binomial regression models adjusted for demographic and clinical covariates.</p><p><strong>Results: </strong>We included 2022 individuals diagnosed with SLE and 20,019 matched reference individuals. 83.8% of patients were female, with an average age of 47.1 years. Even at baseline, patients with SLE exhibited significantly higher healthcare utilisation compared to references for all outcomes which continued throughout the 5-year follow-up. Patients with SLE had approximately 12 annual GP contacts until 1.5 year before diagnosis, where the contact rate increased substantially. Reference individuals consistently had about 4 contacts per year. The incidence rate ratio was approximately 3 during the 5 to 1.5 years preceding diagnosis, increasing to 5.20 (95% confidence interval 4.95-5.46) in the last 6 months before diagnosis.</p><p><strong>Conclusions: </strong>Increased healthcare utilisation years before SLE diagnosis suggests that early symptoms are present and prompt medical attention long before formal diagnosis. These findings highlight the potential for earlier identification of SLE, underscoring the need for improved diagnostic strategies to reduce delays and enhance patient outcomes.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498080","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":"Methotrexate continuation increases fracture risk in patients who sustained lower limb insufficiency fractures.","authors":"Barbara Hauser, Andrew Merriman, Jonathan Foley, Janardhana Golla, Euan McRorie, Stuart H Ralston","doi":"10.1016/j.ard.2025.01.047","DOIUrl":"https://doi.org/10.1016/j.ard.2025.01.047","url":null,"abstract":"<p><strong>Objectives: </strong>Two recent case series and previous case reports have described methotrexate (MTX)-associated insufficiency fractures, so called methotrexate osteopathy (MTXO). Our aim was to assess whether the continuation of MTX after an insufficiency fracture impacts future fracture risk.</p><p><strong>Methods: </strong>Retrospective single-centre case note review of patients who suffered MTXO insufficiency fractures. We assessed the occurrence of subsequent fractures and evaluated fracture healing in patients who either continued or discontinued MTX following the initial fracture.</p><p><strong>Results: </strong>We identified 33 patients with characteristic MTXO lower limb insufficiency fractures. The mean MTX dose was 20 ± 5.9 mg weekly with average treatment duration of 10.7 ± 6.2 years. MTX was continued in 21 out of 32 patients following the initial insufficiency fracture. Almost all patients (95.2%) who continued methotrexate sustained either further insufficiency (67%) or major osteoporotic (33%) fractures. There were significantly fewer fractures (3 out of 11, 27.3%) in the group that stopped MTX after the initial insufficiency fracture (χ² = (1, N = 32) = 13.4; P < .001). A Kaplan-Meier analysis showed that significantly increased number of patients who continued MTX after the initial insufficiency fracture sustained a further fracture over time when compared to patients who stopped methotrexate (P = .042). Discontinuation of MTX was associated with greater clinical improvement in pain (77.8% vs 36.4%, P = .036) and weight-bearing capacity (71.4% vs 22.7%, P = .030) during fracture healing.</p><p><strong>Conclusions: </strong>In patients with MTXO insufficiency fractures, continuation of MTX is associated with a high risk of further fracture. It is important to recognise such insufficiency fractures and stop MTX to minimise the future fracture risk.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482098","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":"Mosaic loss of chromosome Y characterises late-onset rheumatoid arthritis and contrasting associations of polygenic risk score based on age at onset.","authors":"Shunsuke Uchiyama, Yuki Ishikawa, Katsunori Ikari, Suguru Honda, Keiko Hikino, Eiichi Tanaka, Yoichiro Kamatani, Takahisa Gono, Giulio Genovese, Masataka Kuwana, Chikashi Terao","doi":"10.1016/j.ard.2025.01.034","DOIUrl":"https://doi.org/10.1016/j.ard.2025.01.034","url":null,"abstract":"<p><strong>Objectives: </strong>Mosaic chromosomal alterations (mCAs) increase with age and are associated with age-related diseases. The association between mCAs and rheumatoid arthritis (RA), particularly late-onset RA (LORA), has not been explored.</p><p><strong>Methods: </strong>mCAs were detected in peripheral blood samples from 2 independent Japanese datasets (Set 1: 2107 RA cases and 86,998 controls; Set 2: 2359 RA cases and 86,998 controls). The associations between mCAs and RA were evaluated in each dataset using logistic regression models and meta-analysis. In each dataset, the effect sizes of mosaic loss of Y (mLOY) and polygenic risk score (PRS) of RA in males was evaluated, and a meta-analysis was subsequently performed. The interaction between mLOY and PRS was assessed. These models were applied separately to RA, LORA, and young-onset RA (YORA).</p><p><strong>Results: </strong>mLOY increased significantly in LORA (odds ratio [OR] = 1.43, P = .0070). We observed a negative association between mLOY and YORA (OR = 0.66, P = .0034). On the other hand, we found consistently negative associations of autosomal mCAs or mosaic loss of X with RA, LORA, and YORA. The PRS effect sizes were lower for LORA than for YORA. mLOY with a high cell fraction strengthened the association between PRS and LORA (P = .0036), whereas the association with YORA was independent of mLOY.</p><p><strong>Conclusions: </strong>LORA was characterised by the presence of a high burden of mLOY. The observed interaction between mLOY and PRS in LORA, but not in YORA, supports different gene-environment interactions between the subsets. These data suggest that distinct pathophysiological mechanisms underlie the development of LORA and YORA.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476229","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":"Effectiveness and safety of the recombinant zoster vaccine in individuals ≥50 years of age with rheumatoid arthritis: a matched cohort and self-controlled case series study.","authors":"Emily Rayens, Lina S Sy, Lei Qian, Jun Wu, Bradley K Ackerson, Yi Luo, Yanjun Cheng, Antony T Lin, Zendi Solano, Justine De Jesus, Britta Amundsen, Ana Florea, Jennifer H Ku, Elizabeth Chmielewski-Yee, Driss Oraichi, Harry Seifert, Huifeng Yun, Hung Fu Tseng","doi":"10.1016/j.ard.2025.01.045","DOIUrl":"https://doi.org/10.1016/j.ard.2025.01.045","url":null,"abstract":"<p><strong>Objectives: </strong>In an interim analysis, we evaluated vaccine effectiveness (VE) against herpes zoster (HZ) and postherpetic neuralgia (PHN) and safety of recombinant zoster vaccine (RZV) in adults aged ≥50 years with rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>VE was assessed using a retrospective matched cohort analysis of Kaiser Permanente Southern California members aged ≥50 years with RA receiving 2 RZV doses (≥4 weeks apart) and matched up to 1:3 to RZV-unvaccinated individuals. Stratified Cox proportional hazards regression was used to estimate adjusted hazard ratios and VE against HZ and PHN. Safety was assessed using a self-controlled case series analysis of chart-confirmed RA flare within 30 days after any RZV vaccination versus comparison periods. The relative risk (RR) was estimated using conditional Poisson regression.</p><p><strong>Results: </strong>In adults ≥50 years with RA (2-dose vaccinated: 1926; unvaccinated: 5746), the adjusted VE of 2 RZV doses against HZ was 60.7% (95% CI, 41.0%-73.8%); in a subgroup analysis among those who received 2 doses 4 weeks to 6 months apart, VE against HZ was 57.9% (95% CI, 34.4%-73.0%). Adjusted VE of 2 RZV doses against PHN was 88.7% (95% CI, 12.1%-98.5%). Among 2606 adults with RA who received ≥1 RZV dose, no increased risk of RA flares within 30 days after RZV vaccination was observed (RR, 1.02; 95% CI, 0.75-1.37).</p><p><strong>Conclusions: </strong>Among adults ≥50 years with RA, 2 RZV doses provided protection against HZ and PHN. The study did not observe an increased risk of RA flares within 30 days following RZV vaccination.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466734","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":"Increasing the number of minor salivary glands from patients with Sjögren's disease improves the diagnostic and measurement precision of the histological focus score.","authors":"Konstantinos Tryposkiadis, Saba Nayar, Valentina Pucino, Charlotte G Smith, Rachel M Brown, Timothy Bates, Simon J Bowman, Alice Sitch, Malcolm Price, Francesca Barone, Jon Deeks, Benjamin A Fisher","doi":"10.1016/j.ard.2025.01.038","DOIUrl":"https://doi.org/10.1016/j.ard.2025.01.038","url":null,"abstract":"<p><strong>Objectives: </strong>Minor salivary gland (MSG) biopsy has an important role in Sjögren's disease diagnosis and research. MSGs show within-patient variation in number of lymphocytic foci per unit area, but the optimal number of MSGs required to balance reproducibility and clinical acceptability has not been determined.</p><p><strong>Methods: </strong>Monte Carlo simulations were performed to investigate impact of MSG number on (i) diagnosis based on focus score (FS) ≥1; (ii) reproducibility, defined as the extent to which 2 FS measurements obtained from 2 within-patient biopsies are the same, assuming no systematic differences have occurred in between biopsies; and (iii) smallest sample size required to detect a clinically meaningful difference in FS. Data simulation was repeated for different MSG numbers (range, 2-7).</p><p><strong>Results: </strong>Higher reproducibility was noted for every unit increase in MSG number, with the median absolute difference between 2 within-patient FS measurements decreasing from 1.05 (SD = 0.25) with 2 glands to 0.52 (SD = 0.12) with 7 glands. MSG number influenced the probability of a simulated patient receiving a FS ≥1, increasing from a median of 0.67 with 2 glands to 0.77 with ≥5 glands. MSG number influenced clinical trial sample sizes. For example, 80% statistical power to detect a 40% FS reduction required a sample size per group of 62 with 2 glands and 25 with 7 glands.</p><p><strong>Conclusions: </strong>For a diagnostic threshold of FS ≥1, a minimum of 5 glands should ideally be targeted. For continuous FS values, a larger number of MSGs (eg, 6) will increase reproducibility further and reduce clinical trial sample size requirements.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447858","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}