Arthritis & Rheumatology最新文献

{"title":"Baricitinib Improves Bone Properties and Biomechanics in Patients With Rheumatoid Arthritis: Results of the Prospective Interventional BARE BONE Trial","authors":"David Simon,&nbsp;Ioanna Minopoulou,&nbsp;Stephan Kemenes,&nbsp;Sara Bayat,&nbsp;Koray Tascilar,&nbsp;Melek Yalcin Mutlu,&nbsp;Larissa Valor-Méndez,&nbsp;Gerhard Krönke,&nbsp;Axel J. Hueber,&nbsp;Georg Schett,&nbsp;Arnd Kleyer","doi":"10.1002/art.42617","DOIUrl":"10.1002/art.42617","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Rheumatoid arthritis (RA) is characterized by erosive joint damage, deterioration of bone mass, and biomechanics. Preclinical evidence suggests a beneficial effect of Janus kinase inhibition (JAKi) on bone properties, but clinical data are scarce to date. In this study, we evaluated the effect of JAKi through baricitinib (BARI) on 1) volumetric bone mineral density (vBMD), bone microstructure, biomechanics, and erosion repair and 2) synovial inflammation in RA patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Prospective, single-arm, interventional, open-label, single-center phase 4 study in RA patients with pathological bone status and clinical indication of JAKi (BARE BONE trial). Participants received BARI (4 mg/day) over 52 weeks. To assess bone properties and synovial inflammation, high-resolution computed tomography scans and magnetic resonance imaging were performed at baseline (BL), week 24, and week 52. Clinical response and safety were monitored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty RA patients were included. BARI significantly improved disease activity (Disease Activity Score in 28 joints using the erythrocyte sedimentation rate: 4.82 ± 0.90 to 2.71 ± 0.83) and synovial inflammation (RAMRIS synovitis score: 5.3 [4.2] to 2.7 [3.5]). We observed a significant improvement in trabecular vBMD with a mean change of 6.11 mgHA/mm³ (95% confidence interval [95% CI] 0.01–12.26). Biomechanical properties also improved with mean change from baseline in estimated stiffness of 2.28 kN/mm (95% CI 0.30–4.25) and estimated failure load of 98.8 N (95% CI 15.9–181.7). The number and size of erosions in the metacarpal joints remained stable. No new safety signals with BARI treatment were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Bones of RA patients improve with BARI therapy, as shown by an increase in trabecular bone mass and an improvement of biomechanical properties.</p>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"75 11","pages":"1923-1934"},"PeriodicalIF":13.3,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9524120","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":"Identification of Distinct Genetic Profiles of Palindromic Rheumatism Using Whole-Exome Sequencing","authors":"Chenxiang Zheng,&nbsp;Fan Wang,&nbsp;Yue Sun,&nbsp;Zhuochao Zhou,&nbsp;Yijun You,&nbsp;Dongyi He,&nbsp;Xiaoxia Zhu,&nbsp;Lindi Jiang,&nbsp;Cui Lu,&nbsp;Lijun Wu,&nbsp;Hongzhi Wang,&nbsp;Hanying Mei,&nbsp;Ting Zeng,&nbsp;Hui Zheng,&nbsp;Jialing Teng,&nbsp;Honglei Liu,&nbsp;Xiaobing Cheng,&nbsp;Yutong Su,&nbsp;Hui Shi,&nbsp;Qiongyi Hu,&nbsp;Xueming Jian,&nbsp;Aamir Fahira,&nbsp;Qiangzhen Yang,&nbsp;Ke Wang,&nbsp;Yanqin Wen,&nbsp;Zhuo Wang,&nbsp;Jinyan Huang,&nbsp;Chengde Yang,&nbsp;Yongyong Shi,&nbsp;Junna Ye","doi":"10.1002/art.42614","DOIUrl":"10.1002/art.42614","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Previous studies have underlined the genetic susceptibility in the pathogenesis of palindromic rheumatism (PR), but the known PR loci only partially explain the disease's genetic background. We aimed to genetically identify PR by whole-exome sequencing (WES).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multicenter prospective study was conducted in 10 Chinese specialized rheumatology centers between September 2015 and January 2020. WES was performed in 185 patients with PR and in 272 healthy controls. PR patients were divided into PR subgroups who were negative for anti–citrullinated protein antibody (ACPA−) and positive for ACPA (ACPA+) according to ACPA titer (cutoff value 20 IU/liter). We conducted whole-exome association analysis for the WES data. We used HLA imputation to type HLA genes. In addition, we used the polygenic risk score to measure the genetic correlations between PR and rheumatoid arthritis (RA) and the genetic correlations between ACPA− PR and ACPA+ PR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 185 patients with PR enrolled in our study, 50 patients (27.02%) were ACPA+ and 135 PR patients (72.98%) were ACPA−. We identified 8 novel loci (in the ACPA− PR group: ZNF503, RPS6KL1, HOMER3, HLA–DRA; in the ACPA+ PR group: RPS6KL1, TNPO2, WASH2P, FANK1) and 3 HLA alleles (in the ACPA− PR group: HLA–DRB1*0803 and HLA–DQB1; in the ACPA+ PR group: HLA–DPA1*0401) that were associated with PR and that surpassed genome-wide significance (<i>P</i> &lt; 5 × 10⁻⁸). Furthermore, polygenic risk score analysis showed that PR and RA were not similar (R² &lt; 0.025), whereas ACPA+ PR and ACPA− PR showed a moderate genetic correlation (0.38 &lt; R² &lt; 0.8).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrated the distinct genetic background between ACPA− and ACPA+ PR patients. Additionally, our findings strengthened that PR and RA were not genetically similar.</p>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"75 11","pages":"1947-1957"},"PeriodicalIF":13.3,"publicationDate":"2023-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9859941","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":"Body Mass Index and the Risk of Rheumatic Disease: Linear and Nonlinear Mendelian Randomization Analyses","authors":"Torgny Karlsson,&nbsp;Fatemeh Hadizadeh,&nbsp;Mathias Rask-Andersen,&nbsp;Åsa Johansson,&nbsp;Weronica E. Ek","doi":"10.1002/art.42613","DOIUrl":"10.1002/art.42613","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Although the association between obesity and risk of rheumatic disease is well established, the precise causal relation has not been conclusively proven. Here, we estimate the causal effect of body mass index (BMI) on the risk of developing 5 different rheumatic diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Linear and nonlinear mendelian randomization (MR) were used to estimate the effect of BMI on risk of rheumatic disease, and sex-specific effects were identified. Analyses were performed in 361,952 participants from the UK Biobank cohort for 5 rheumatic diseases: rheumatoid arthritis (n = 8,381 cases), osteoarthritis (n = 87,430), psoriatic arthropathy (n = 933), gout (n = 13,638), and inflammatory spondylitis (n = 4,328).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Using linear MR, we found that 1 SD increase in BMI increases the incidence rate for rheumatoid arthritis (incidence rate ratio [IRR] 1.52 [95% confidence interval (95% CI) 1.36–1.69]), osteoarthritis (IRR 1.49 [95% CI 1.43–1.55]), psoriatic arthropathy (IRR 1.80 [95% CI 1.31–2.48]), gout (IRR 1.73 [95% CI 1.56–1.92]), and inflammatory spondylitis (IRR 1.34 [95% CI 1.14–1.57]) in all individuals. BMI was found to be a stronger risk factor in women compared to men for psoriatic arthropathy (<i>P</i> for sex interaction = 3.3 × 10⁻⁴) and gout (<i>P</i> for sex interaction = 4.3 × 10⁻³), and the effect on osteoarthritis was stronger in premenopausal compared to postmenopausal women (<i>P</i> = 1.8 × 10⁻³). Nonlinear effects of BMI were identified for osteoarthritis and gout in men, and for gout in women. The nonlinearity for gout was also more extreme in men compared to women (<i>P</i> = 0.03).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Higher BMI causes an increased risk for rheumatic disease, an effect that is more pronounced in women for both gout and psoriatic arthropathy. The novel sex- and BMI-specific causal effects identified here provide further insight into rheumatic disease etiology and mark an important step toward personalized medicine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"75 11","pages":"2027-2035"},"PeriodicalIF":13.3,"publicationDate":"2023-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9560910","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":"The Clinical Impact of Electronic Patient-Reported Outcome Measures in the Remote Monitoring of Inflammatory Arthritis: A Systematic Review and Meta-analysis","authors":"Nikita Arumalla,&nbsp;Chun K. D. Chan,&nbsp;Mark Gibson,&nbsp;Yik L. Man,&nbsp;Maryam A. Adas,&nbsp;Sam Norton,&nbsp;James B. Galloway,&nbsp;Toby Garrood","doi":"10.1002/art.42559","DOIUrl":"10.1002/art.42559","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The inflammatory arthritides (IAs) make up a significant proportion of conditions followed up in rheumatology clinics. These patients require regular monitoring, but this is increasingly difficult with rising patient numbers and demand on clinics. Our objective is to evaluate the clinical impact of electronic patient-reported outcome measures (ePROMs) as a digital remote-monitoring intervention on disease activity, treatment decisions, and health care resource use in patients with IA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Five databases (MEDLINE, Embase, PubMed, Cochrane Library, and Web of Science) were searched, with randomized controlled trials and (nonrandomized) controlled clinical trials included, and meta-analysis and forest plots conducted for each outcome. Risk of bias was assessed using the Risk of Bias-2 tool and Risk of Bias in Nonrandomized Studies of Interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight studies were included with a total of 4,473 patients, with seven studies assessing patients with rheumatoid arthritis. Compared with control, the disease activity in the ePROM group was lower (standardized mean difference [SMD] −0.15; 95% confidence interval [CI] −0.27 to −0.03) and rates of remission/low disease activity were higher (odds ratio1.65; 95% CI 1.02–2.68), but five of eight studies provided additional combined interventions (e.g., disease education). Fewer face to face visits were needed in the remote ePROM group (SMD −0.93; 95% CI −2.14–0.28).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Most studies were at high risk of bias with significant heterogeneity in design, but our results suggest there is an advantage in using ePROM monitoring in patients with IAs, with the potential for reduction in health care resource use without detrimental impact in disease outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"75 11","pages":"1892-1903"},"PeriodicalIF":13.3,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301105","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 the TYK2/JAK1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial","authors":"Philip Mease,&nbsp;Philip Helliwell,&nbsp;Paula Silwinska-Stanczyk,&nbsp;Malgorzata Miakisz,&nbsp;Andrew Ostor,&nbsp;Elena Peeva,&nbsp;Michael S. Vincent,&nbsp;Qiankun Sun,&nbsp;Vanja Sikirica,&nbsp;Randall Winnette,&nbsp;Ruolun Qiu,&nbsp;Gang Li,&nbsp;Gang Feng,&nbsp;Jean S. Beebe,&nbsp;David A. Martin","doi":"10.1002/art.42519","DOIUrl":"10.1002/art.42519","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Brepocitinib is a TYK2/JAK1 inhibitor in development for the treatment of several immunologic diseases. The efficacy and safety of oral brepocitinib were assessed in participants with moderately-to-severely active psoriatic arthritis (PsA) for up to 52 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this placebo-controlled, dose-ranging, phase IIb study, participants were randomized to receive 10 mg, 30 mg, or 60 mg of brepocitinib once daily or placebo, advancing to 30 mg or 60 mg of brepocitinib once daily at week 16. The primary endpoint was the response rate according to the American College of Rheumatology criteria for 20% improvement (ACR20) in disease activity at week 16. Secondary endpoints included response rates according to the ACR50/ACR70 response criteria, 75% and 90% improvement in the Psoriasis Area and Severity Index (PASI75/PASI90) score, and minimal disease activity (MDA) at weeks 16 and 52. Adverse events were monitored throughout the study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 218 participants were randomized and treated. At week 16, the brepocitinib 30 mg and 60 mg once daily groups had significantly greater ACR20 response rates (66.7% [<i>P</i> = 0.0197] and 74.6% [<i>P</i> = 0.0006], respectively), versus the placebo group (43.3%), and significantly higher ACR50/ACR70, PASI75/PASI90, and MDA response rates. Response rates were maintained or improved through week 52. Adverse events were mostly mild/moderate; serious adverse events (15) in 12 participants (5.5%) included infections in 6 participants (2.8%) in the brepocitinib 30 mg and 60 mg once daily groups. No major adverse cardiovascular events or deaths occurred.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Treatment with brepocitinib at dosages of 30 mg and 60 mg once daily was superior to placebo at reducing signs and symptoms of PsA. Brepocitinib was generally well tolerated throughout the 52-week study, with a safety profile consistent with those found in other brepocitinib clinical trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"75 8","pages":"1370-1380"},"PeriodicalIF":13.3,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.42519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5905810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Biomarker Responses to BI 655064, an Antagonistic Anti-CD40 Antibody, in Patients With Active Lupus Nephritis: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial","authors":"David R. Jayne,&nbsp;Jürgen Steffgen,&nbsp;Juanita Romero-Diaz,&nbsp;Ingeborg Bajema,&nbsp;Dimitrios T. Boumpas,&nbsp;Kajohnsak Noppakun,&nbsp;Hirofumi Amano,&nbsp;Harold Michael Gomez,&nbsp;Bancha Satirapoj,&nbsp;Yingyos Avihingsanon,&nbsp;Ratana Chawanasuntorapoj,&nbsp;Magdalena Madero,&nbsp;Beata Naumnik,&nbsp;Rhona Recto,&nbsp;Nora Fagan,&nbsp;Ivette Revollo,&nbsp;Jing Wu,&nbsp;Sudha Visvanathan,&nbsp;Richard Furie","doi":"10.1002/art.42557","DOIUrl":"10.1002/art.42557","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To characterize its dose-response relationship, BI 655064 (an anti-CD40 monoclonal antibody) was tested as an add-on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 121 patients were randomized (2:1:1:2) to receive placebo or BI 655064 120, 180, or 240 mg and received a weekly loading dose for 3 weeks followed by dosing every 2 weeks for the 120 and 180 mg groups, and 120 mg weekly for the 240 mg group. The primary endpoint was complete renal response (CRR) at week 52. Secondary endpoints included CRR at week 26.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A dose-response relationship with CRR at week 52 was not shown (BI 655064 120 mg, 38.3%; 180 mg, 45.0%; 240 mg, 44.6%; placebo, 48.3%). At week 26, 28.6% (120 mg), 50.0% (180 mg), 35.0% (240 mg), and 37.5% (placebo) achieved CRR. The unexpected high placebo response prompted a post hoc analysis evaluating confirmed CRR (cCRR, at weeks 46 and 52). cCRR was achieved in 22.5% (120 mg), 44.3% (180 mg), 38.2% (240 mg), and 29.1% (placebo) of patients. Most patients reported ≥1 adverse event (BI 655064, 85.7–95.0%; placebo, 97.5%), most frequently infections and infestations (BI 655064 61.9–75.0%; placebo 60%). Compared with other groups, higher rates of serious (20% vs. 7.5–10%) and severe infections (10% vs. 4.8–5.0%) were reported with 240 mg BI 655064.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The trial failed to demonstrate a dose-response relationship for the primary CRR endpoint. Post hoc analyses suggest a potential benefit of BI 655064 180 mg in patients with active LN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"75 11","pages":"1983-1993"},"PeriodicalIF":13.3,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10019832","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":"Antibodies to Neutrophil Extracellular Traps: Novel Markers for the Antiphospholipid Syndrome","authors":"David S. Pisetsky","doi":"10.1002/art.42548","DOIUrl":"10.1002/art.42548","url":null,"abstract":"In this issue of Arthritis & Rheumatology , a provocative serologic analysis by Zuo et al provides a novel perspective on autoantibody expression in patients with antiphospholipid antibodies (aPL) (1). As the data from a large patient cohort indicate, patients whose serum is persistently positive for APL, including those with the antiphospholipid syndrome (APS), produce IgM and IgG antibodies to neutrophil extracellular traps (NETs), a large DNA-rich structure released by activated neutrophils (2,3). Furthermore, these patients can display antibodies to DNA and nucleosomes, both speci fi c markers of systemic lupus erythema-tosus (SLE). Demonstrating intriguing similarity in immunologic fi ndings between APS and SLE, the study supports the importance of anti-NETs in both autoimmunity and immunothrombosis, the critical junction where in fl ammation and thrombosis inter-sect (4).","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"75 8","pages":"1331-1333"},"PeriodicalIF":13.3,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5688701","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":"Weighing the Risks and Benefits of Pneumocystis Jirovecii Pneumonia Prophylaxis in Rituximab Users","authors":"Zachary S. Wallace,&nbsp;Michael Putman","doi":"10.1002/art.42562","DOIUrl":"10.1002/art.42562","url":null,"abstract":"Severe infections are a leading cause of morbidity, hospitalization, and mortality for patients with rheumatic diseases. In a recent clinical trial in antineutrophil cytoplasmic antibody (ANCA) – associated vasculitis (AAV), for instance, over 20% of participants had ≥ 1 serious infection over 44 months (1), and in a recent giant cell arteritis trial, up to 12% of participants had a serious infection over 12 months (2). Several factors in fl uence the risk of severe infection, including patient age, the immunologic target(s) of the treatment, the presence of end-organ damage related to the rheumatic disease (e.g., lung or kidney disease), and the patient ’ s comorbidities. Preventing Pneumocystis jirovecii pneumonia (PJP) is of particular interest for rheumatologists. PJP is often severe among patients with rheumatic diseases, with mortality rates exceeding 40% (3). Prophylaxis with trimethoprim/sulfamethoxazole (TMP/SMX) has been associated with reduced mortality in this population (4,5). Acknowledging this, the recent American College of Rheumatology (ACR)/Vasculitis Foundation (VF) guideline for the management of AAV conditionally recommends prophylaxis to prevent PJP in patients receiving rituximab or cyclophosphamide treatment (6).","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"75 11","pages":"1904-1906"},"PeriodicalIF":13.3,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10046224","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":"Rheumatoid Arthritis–Specific Autoimmunity in the Lung Before and at the Onset of Disease","authors":"Vijay Joshua,&nbsp;Malena Loberg Haarhaus,&nbsp;Aase Hensvold,&nbsp;Heidi Wähämaa,&nbsp;Christina Gerstner,&nbsp;Monika Hansson,&nbsp;Lena Israelsson,&nbsp;Ragnhild Stålesen,&nbsp;Magnus Sköld,&nbsp;Johan Grunewald,&nbsp;Lars Klareskog,&nbsp;Caroline Grönwall,&nbsp;Bence Réthi,&nbsp;Anca Catrina,&nbsp;Vivianne Malmström","doi":"10.1002/art.42549","DOIUrl":"10.1002/art.42549","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The lung is implicated as a site for breach of tolerance prior to onset of seropositive rheumatoid arthritis (RA). To substantiate this, we investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from untreated early RA patients and anti–citrullinated protein antibody (ACPA)–positive individuals at risk for developing RA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single B cells (n = 7,680) were phenotyped and isolated from BAL samples from individuals at risk of RA (n = 3) and at RA diagnosis (n = 9). The immunoglobulin variable region transcripts were sequenced and selected for expression as monoclonal antibodies (n = 141). Monoclonal ACPAs were tested for reactivity patterns and binding to neutrophils.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Using our single-cell approach, we found significantly increased proportions of B lymphocytes in ACPA+ compared to ACPA– individuals. Memory and double-negative B cells were prominent in all subgroups. Upon antibody re-expression, 7 highly mutated citrulline-autoreactive clones originating from different memory B cell subsets were identified, both in individuals at risk of RA and early RA patients. Lung IgG variable gene transcripts from ACPA+ individuals carried frequent mutation-induced <i>N</i>-linked Fab glycosylation sites (<i>P</i> &lt; 0.001), often in the framework 3 of the variable region. Two of the lung ACPAs bound to activated neutrophils, 1 from an individual at risk of RA and 1 from an early RA patient.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>T cell–driven B cell differentiation resulting in local class switching and somatic hypermutation are evident in lungs before as well as in early stages of ACPA+ RA. Our findings add to the notion of lung mucosa being a site for initiation of citrulline autoimmunity preceding seropositive RA.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"75 11","pages":"1910-1922"},"PeriodicalIF":13.3,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9933149","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":"Immediate Open Access: The Good, the Bad, and the Impact on Academic Society Publishing","authors":"Amr H. Sawalha,&nbsp;Daniel H. Solomon,&nbsp;Kelli D. Allen,&nbsp;Patricia Katz,&nbsp;Ed Yelin","doi":"10.1002/art.42522","DOIUrl":"10.1002/art.42522","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"75 7","pages":"1083-1084"},"PeriodicalIF":13.3,"publicationDate":"2023-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6095156","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}