ACR open rheumatology最新文献

{"title":"Burden of Emergency Department Visits and Their Outcomes Among Patients With Rheumatoid Arthritis: Insights From the Nationwide Emergency Department Sample.","authors":"Vishwesh Bharadiya, Parul Berry, Aman Dev Singh, Dominique Feterman, Grant Hughes, Alison Bays, Rachael Stovall, Rashmi Dhital, Namrata Singh","doi":"10.1002/acr2.70043","DOIUrl":"https://doi.org/10.1002/acr2.70043","url":null,"abstract":"<p><strong>Objective: </strong>Patients with rheumatoid arthritis (RA) frequently visit emergency departments (EDs), but their clinical characteristics and admission factors are poorly understood. Our study investigates the epidemiology and outcomes of ED visits among patients with RA using the Nationwide Emergency Department Sample (NEDS).</p><p><strong>Methods: </strong>This cross-sectional study used the 2019 NEDS data to identify RA-related ED visits using International Classification of Disease, Tenth Revision codes M05.X or M06.X. RA-related ED visits were defined as encounters in which RA was recorded in any diagnostic position. Demographics, clinical features, and comorbidities were compared between RA and non-RA ED visits. Racial variations were assessed, and multivariable logistic regression identified factors associated with inpatient admission.</p><p><strong>Results: </strong>We identified 905,811 (0.8%) ED visits for adults aged ≥18 years with RA. Compared to non-RA visits, RA ED visits had a higher proportion of patients aged ≥65 years, women, White patients, and Medicare-insured individuals with a greater comorbidity burden. Admission rates were 46% for RA visits versus 16% for non-RA visits. Black and Hispanic patients with RA were younger than White patients and more likely to belong to the lowest income quartile. Older age, male sex, and comorbidities were associated with higher admission odds, whereas Black race, lowest income quartile, and Medicaid coverage correlated with lower odds of admission. Septicemia was the most common primary ED diagnosis in patients with RA.</p><p><strong>Conclusion: </strong>Patients with RA visiting the ED were older, had a higher comorbidity burden, and were three times more likely to be admitted than patients without RA. Black patients and those in the lowest income quartile had lower odds of admission, highlighting potential disparities and the need for targeted interventions to improve health equity.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":"7 5","pages":"e70043"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the Impact of Tofacitinib Treatment on Weight and Body Mass Index in Patients With Rheumatoid Arthritis.","authors":"Jürgen Wollenhaupt, Jacques Morel, Claire Daien, Adeline Ruyssen-Witrand, Cédric Lukas, Christophe Richez, Andrea Shapiro, Douglass S Chapman, Magali Cros, Jose L Rivas, Gustavo Citera","doi":"10.1002/acr2.70040","DOIUrl":"https://doi.org/10.1002/acr2.70040","url":null,"abstract":"<p><strong>Objectives: </strong>This post hoc analysis evaluated change from baseline (Δ) in weight/body mass index (BMI) and association with disease activity or lipid changes in tofacitinib-treated patients with rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>Data up to month 12 were pooled from eight phase 3 and 3b/4 studies of patients with RA receiving tofacitinib 5 or 10 mg twice daily or tofacitinib 11 mg modified-release once daily (alone or combined with conventional synthetic disease-modifying antirheumatic drugs), or placebo. Assessments included Δweight/BMI and the proportion of patients with weight gain ≥5%, at months 3, 6, and 12. Correlations between ∆weight/∆BMI and baseline/∆Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]), baseline C-reactive protein (CRP), and ∆lipids were assessed. Statistical analysis included a longitudinal linear mixed model for repeated measures.</p><p><strong>Results: </strong>The analysis included 5,335 patients (tofacitinib 5 mg twice daily [n = 2,349], 10 mg twice daily [n = 1,611], 11 mg once daily [n = 694], and placebo [n = 681]). Increases in least squares mean Δweight and ΔBMI were significantly greater (P < 0.05) at months 3 and 6 with all tofacitinib doses versus placebo; increases continued to month 12. Significantly greater (at least P < 0.05) proportions of tofacitinib-treated patients (all doses) had weight gain ≥5% at months 3 and 6 versus placebo. There were weak correlations between weight/BMI changes with tofacitinib and DAS28-4(ESR), baseline CRP, or lipid changes.</p><p><strong>Conclusion: </strong>Patients receiving tofacitinib experienced weight and BMI changes (primarily increases) over time, with weak correlations with disease activity or lipids.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":"7 5","pages":"e70040"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrovascular Involvement in Systemic Sclerosis.","authors":"Maurizio Cutolo, Tamara Vojinovic, Sabrina Paolino, Rosanna Campitiello, Vanessa Smith","doi":"10.1002/acr2.70032","DOIUrl":"https://doi.org/10.1002/acr2.70032","url":null,"abstract":"<p><p>Systemic sclerosis (SSc) is a chronic autoimmune rheumatic disease characterized by vascular damage, immune system dysregulation and fibrosis. The hallmark features include microvascular alterations and progressive tissue fibrosis, affecting skin, internal organs as well central and peripheral nervous system, adding to the disease's complexity and influencing overall outcomes. Of note, SSc has also been linked to macrovascular and cardiovascular involvement, including cerebrovascular damage as observed in stroke. Indeed, advanced neuroimaging is highly recommended for assessing cerebrovascular status in overt SSc to evaluate the complex interactions between cerebrovascular dysfunction and brain tissue damage and/or inflammation. Cerebral vasospasm detected by angiography, as well as an increase in subclinical cerebrovascular atherosclerosis observed by ultrasonography (carotid intimal medial thickness), are predictive for elevated stroke risk. Furthermore, a significant brain hypoperfusion detected by magnetic resonance imaging, along with white matter focal and/or diffuse signal abnormalities in SSc, have been found associated with concomitant peripheral microvascular damage detectable by \"Active\" and \"Late\" nail fold video capillaroscopy scleroderma patterns. Finally, the presence of calcifications in small arteries and arterioles found postmortem in the brain of SSc patients reinforces the hypothesis that SSc is associated with brain vascular remodeling. Furthermore, the current state of art shows an increased risk of cerebrovascular events in the SSc, confirmed by neuroimaging. Given the lack of updated comprehensive reviews on cerebrovascular involvement in SSc, we gathered the most relevant evidence on central nervous system damage, highlighting the underlying mechanisms, clinical implications, and potential advantages that neuroimaging may provide for its early detection.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":"7 4","pages":"e70032"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methotrexate osteopathy: Old description, but still important to know.","authors":"François Robin, Alexia Leloix, Pascal Guggenbuhl, Virginie Gandemer, Jacinthe Bonneau-Lagacherie","doi":"10.1002/acr2.70039","DOIUrl":"https://doi.org/10.1002/acr2.70039","url":null,"abstract":"","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":"7 4","pages":"e70039"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass-Forming Variants in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Diagnostic Complexities in Granulomatous Disease. A Case Report.","authors":"Benedetta Fazzi, Elena Treppo, Simone Longhino, Maria Pillon, Luca Quartuccio","doi":"10.1002/acr2.70038","DOIUrl":"10.1002/acr2.70038","url":null,"abstract":"<p><p>A middle-aged woman presented with a granulomatous breast lesion in 2018. By 2021, antibiotic-resistant pneumonia led to the discovery of granulomatous inflammation in the lung and thyroid. Initially misdiagnosed as Erdheim-Chester disease (ECD), she was treated with interferon without success. Histopathology later ruled out ECD, suggesting an unspecified granulomatous disease, with granulomatosis with polyangiitis (GPA) initially excluded due to negative antineutrophil cytoplasmic antibodies (ANCAs) and foamy histiocytes. In 2023, repeated lung biopsy and PR3-ANCA positivity led to a revised diagnosis of mass-forming GPA. Rituximab therapy resulted in remission. This case highlights the diagnostic complexity of GPA with atypical histopathological features.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":"7 4","pages":"e70038"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Prognostic and Functional Impact of Multimorbidity in Systemic Sclerosis.","authors":"Jessica L Fairley, Dylan Hansen, Susanna Proudman, Joanne Sahhar, Gene-Siew Ngian, Diane Apostolopoulos, Jennifer Walker, Lauren V Host, Wendy Stevens, Mandana Nikpour, Laura Ross","doi":"10.1002/acr2.70034","DOIUrl":"10.1002/acr2.70034","url":null,"abstract":"<p><strong>Objective: </strong>Our objective was to define the frequency and impact of multimorbidity in systemic sclerosis (SSc).</p><p><strong>Method: </strong>Australian Scleroderma Cohort Study participants meeting American College of Rheumatology/EULAR criteria were included. Charlson Comorbidity Index scores were calculated at each visit, with multimorbidity defined as scores ≥4. Generalized estimating equations were used to model longitudinal data in multivariable models including age, sex, subclass, interstitial lung disease, and pulmonary arterial hypertension status. Survival was analyzed using Cox hazard modeling.</p><p><strong>Results: </strong>Of 2,000 participants, 85% were female, 27% had diffuse SSc, and 20% had multimorbidity. Among those with multimorbidity, key comorbidities were hypertension (81%), dyslipidemia (67%), obstructive lung disease (50%), malignancy (49%), and ischemic heart disease (IHD) (40%). Multimorbidity was associated with worse survival (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.30-1.91, P < 0.01). Renal disease had the largest impact (HR 2.41, 95% CI 1.46-3.98, P < 0.01), followed by left ventricular dysfunction (HR 1.76, 95% CI 1.21-2.57, P < 0.01), anticoagulation (HR 1.64, 95% CI 1.28-2.08, P < 0.01), and IHD (HR 1.45, 95% CI 1.16-1.80, P < 0.01). In multivariable modeling, multimorbidity was associated with poorer physical function (regression coefficient [RC] +0.17 units, 95% CI 0.13-0.21, P < 0.01). Peripheral vascular disease had the largest impact on physical function (RC +0.26 units, 95% CI 0.18-0.34, P < 0.01), followed by left ventricular dysfunction (RC +0.23 units, 95% CI 0.14-0.33, P = 0.01), IHD (RC +0.22 units, 95% CI 0.17-0.28, P < 0.01), and obstructive lung disease (RC +0.19 units, 95% CI 0.14-0.24, P < 0.01).</p><p><strong>Conclusion: </strong>Multimorbidity occurred in 20% of patients in a large SSc cohort and was an important determinant of both prognosis and physical function. Effective treatment of non-SSc morbidity may improve outcomes for patients with SSc. Graphical Abstract. *p-value <0.05. Multimorbidity defined as Charlson Comorbidity Index scores ≥4.</p><p><strong>Abbreviations: </strong>CI (confidence interval), CKD (chronic kidney disease), COPD (chronic obstructive pulmonary disease), HAQ-DI (health assessment questionnaire disability index), HR (hazard ratio), LVEF (left ventricular ejection fraction), IHD (ischaemic heart disease), HR (hazard ratio), IQR (interquartile range), PVD (peripheral vascular disease), SSc (systemic sclerosis).</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":"7 4","pages":"e70034"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoclastogenesis in Patients With Systemic Sclerosis With and Without Calcinosis Cutis.","authors":"Antonia Valenzuela, Guillermo Pérez, Lorinda Chung, Felipe Sánchez, Carolina Iturriaga, Rebeca Montalva, Arturo Borzutzky","doi":"10.1002/acr2.70029","DOIUrl":"10.1002/acr2.70029","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to assess whether the presence of radiographically confirmed calcinosis of the hands in patients with systemic sclerosis (SSc) is associated with increased osteoclastogenesis.</p><p><strong>Methods: </strong>We recruited 20 patients with SSc (10 with calcinosis and 10 without calcinosis) and 10 age- and gender-matched healthy controls. Hand radiographs were scored using the validated Scleroderma Clinical Trials Consortium (SCTC) radiographic severity score for calcinosis. To evaluate osteoclastogenesis, peripheral blood mononuclear cells (PBMCs) were cultured with RANKL and macrophage colony-stimulating factor; osteoclasts were identified using tartrate-resistant acid phosphatase staining. Measures of bone resorption (RANKL, osteoprotegerin [OPG]) and ischemia or endothelial function (vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 [Ang-2]) were also evaluated.</p><p><strong>Results: </strong>Patients with SSc were all women and Hispanic, and the majority (n = 12, 60%) had limited SSc skin type. Mean ± SD age was 55.2 ± 14.8 years; mean ± SD disease duration was 9.5 ± 6.5 years from first non-Raynaud phenomenon symptom. Patients with SSc with calcinosis had more digital ischemia than patients without calcinosis. Median SCTC score in patients with SSc with calcinosis was 11.1 (range 0.7-286). After 9 days in culture, PBMCs from patients with calcinosis originated a significantly higher number of osteoclasts (33.0 ± 20.3 cells/well) than patients without calcinosis (15.3 ± 6.9 cells/well) and healthy individuals (11.2 ± 2.6 cells/well) (P = 0.001). The severity of calcinosis was not correlated with the number of osteoclasts per well (r = 0.27, P = 0.5); however, it was correlated with RANKL (r = 0.82, P = 0.004), RANKL/OPG ratio (r = 0.86, P = 0.002), and Ang-2 levels (r = 0.86, P = 0.002).</p><p><strong>Conclusion: </strong>Calcinosis in patients with SSc is associated with an increased propensity of peripheral blood cells to form osteoclasts. Targeted inhibition of osteoclastogenesis may provide a specific therapeutic option for patients with SSc-associated calcinosis.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":"7 4","pages":"e70029"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac Magnetic Resonance Imaging Findings in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitides: A Systematic Review.","authors":"Ioannis Karageorgiou, Unnati Bhatia, Hazem Alakhras, Berk Celik, Alexandra Halalau","doi":"10.1002/acr2.70026","DOIUrl":"https://doi.org/10.1002/acr2.70026","url":null,"abstract":"<p><strong>Objective: </strong>Our objective was to review the available literature on cardiac magnetic resonance imaging (cMRI) findings in patients with antineutrophil cytoplasmic antibody-associated vasculitides (AAV), evaluate its diagnostic utility, and assess its potential as a screening tool.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, Scopus, and Web of Science from inception to March 29, 2023, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. English-language studies involving adult patients diagnosed with AAV-eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA)-using recognized classification criteria were included. Studies had to report specific cMRI parameters in at least three patients. Three independent reviewers conducted study selection, data extraction, and quality assessment.</p><p><strong>Results: </strong>Of 2,251 studies, 30 met the inclusion criteria, encompassing 1,149 patients with AAV (87% with EGPA, 13% with GPA, and 0.3% with MPA). The mean patient age was 52 ± 5 years, with 50.4% being female. The mean left ventricular ejection fraction (LVEF) was 55.6% ± 11.3%, and 29% of patients had an LVEF less than 50%. Myocardial fibrosis, indicated by late gadolinium enhancement (LGE), was present in 49% of patients, with predominantly subendocardial or endocardial (23%), intramyocardial (14%), and subepicardial (10%) patterns. Patients in remission (26%), when compared to those not in remission (74%), exhibited higher proportions of LGE (55% vs 47%) and glucocorticoid use (77% vs 68%), despite similar rates of abnormal electrocardiograms (44% vs 42%).</p><p><strong>Conclusion: </strong>This systematic review reveals a high prevalence of myocardial fibrosis detected by cMRI in patients with AAV, even during remission. Significant subclinical cardiac involvement may be missed by conventional diagnostic methods, underscoring the utility of cMRI during routine evaluation.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":"7 4","pages":"e70026"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Reported Factors Influencing Clinical Trial Participation: An In-depth Analysis of Patients With Lupus and Rheumatoid Arthritis.","authors":"Aliza Bloostein, Roberto Caricchio","doi":"10.1002/acr2.70035","DOIUrl":"https://doi.org/10.1002/acr2.70035","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE), a chronic systemic autoimmune disease, has only three approved therapies, despite a rapidly expanding number of clinical trials. Trials in SLE struggle to recruit patients and fail to fully enroll. Rheumatoid arthritis (RA), another chronic autoimmune disease, has had more success in clinical trial enrollment. This article's goal is to analyze literature to compare patient perspectives on factors determining clinical trial participation in SLE and RA populations. A literature review regarding patient attitudes, perceptions, perspectives about, and barriers toward clinical trials was conducted. RA literature used more quantitative methods, whereas SLE literature used more qualitative methods. Literature revealed that patients with SLE and patients with RA reported similar factors motivating trial participation, such as altruism, personal benefit, and trust in physician, but patients with SLE were uniquely motivated by strong social networks. In terms of disadvantages to trial participation, patients with SLE and RA similarly reported fear of unknown interventions, complications, and side effects; only in the population of patients with SLE were fears of a disease flare and of not qualifying reported. SLE literature had a specific emphasis on factors influencing Black patient participation. This review informs steps for future research to better evaluate perceptions of clinical trials in patients with SLE and provides a framework for methods to increase SLE trial participation, including recognizing fear of changing treatment regimen as an explanation for the paucity of SLE trial participation, incorporating clinical trials as usual care for patients with SLE, and using less stringent inclusion and exclusion criteria for trials.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":"7 4","pages":"e70035"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and Safety of Oral Pyrophosphate in Systemic Sclerosis Patients-A Pilot Study.","authors":"Gergely Bodor, Márta Bocskai, Ágnes Dura, László Kovács, András Váradi, Eszter Kozák","doi":"10.1002/acr2.70036","DOIUrl":"https://doi.org/10.1002/acr2.70036","url":null,"abstract":"<p><strong>Objective: </strong>Calcinosis is a manifestation of systemic sclerosis with a severe negative impact on quality of life. Efforts to find a treatment for calcinosis have been hindered by our limited understanding of the underlying pathomechanism. We propose that extracellular pyrophosphate deficiency may have a causal role in the formation of these mineralized deposits, because pyrophosphate inhibits the deposition of hydroxyapatite-the major constituent of calcinosis-and supplementing pyrophosphate may have therapeutic potential in the treatment of calcinosis.</p><p><strong>Methods: </strong>Systemic sclerosis patients were treated with a single dose of 50 mg/kg disodium pyrophosphate (cohort 1, n = 10), or a daily dose of 25 mg/kg disodium pyrophosphate for seven consecutive days (cohort 2, n = 10). Safety of oral pyrophosphate treatment was assessed with special focus on gastrointestinal tolerance, serum phosphate and calcium levels, and potential electrocardiography abnormalities. Absorption kinetics and peak plasma pyrophosphate concentrations were measured by the adenosine triphosphate sulfurylase method.</p><p><strong>Results: </strong>Gastrointestinal adverse effects associated with oral pyrophosphate treatment were rare and mild. The only consistent abnormality among the serum parameters studied was a transient elevation of serum phosphate levels (change: 0.2 to 0.62 and 0.15 to 0.44 mmol/L in cohorts 1 and 2, respectively). Based on electrocardiography results, both doses can be regarded as safe in terms of corrected QT interval prolongation in short-term treatment. Serum pyrophosphate levels increased significantly in both cohorts.</p><p><strong>Conclusion: </strong>Oral pyrophosphate treatment was found to be safe in patients with systemic sclerosis and resulted in elevated plasma concentrations comparable to results obtained in healthy volunteers. This provides rationale to test the therapeutic potential of pyrophosphate against calcinosis.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":"7 4","pages":"e70036"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}