Pub Date : 2025-01-01DOI: 10.1016/S2665-9913(24)00235-2
Sherry Yang BS , Leah Santacroce MS , Jamie E Collins PhD , Candace H Feldman MD ScD
<div><h3>Background</h3><div>Structural racism lies at the root of inequities; however its impact on rheumatology care is understudied. Redlining was a US federal government-sponsored practice that mapped areas with high concentrations of Black and immigrant residents as hazardous for investment. We aimed to investigate the association of historical redlining and present-day racialised economic segregation, on health-care utilisation among individuals with rheumatic conditions in the US state of Massachusetts and surrounding areas.</div></div><div><h3>Methods</h3><div>This retrospective observational cohort study used multihospital data from the Mass General Brigham Research Patient Data Registry to identify individuals aged ≥ 18 years living in Massachusetts and surrounding areas, with two or more International Classification of Diseases codes for a rheumatic condition. Individuals were included if they received care between Jan 1, 2000, and May 1, 2023, at rheumatology practices affiliated with Mass General Brigham (Boston, MA, USA). Addresses were geocoded and overlaid with 1930s Home Owners' Loan Corporation (HOLC) redlining files. The Index of Concentration at the Extremes (ICE) for combined racial and income polarisation was constructed from US Census data. We used multilevel, multinomial logistic regression models to examine the odds of health-care utilisation separately by historical HOLC grade (A [best] to D [hazardous]) and ICE quintile (most deprived [1] to most privileged [5] race and income), adjusting for demographics, insurance, and comorbidities. People with lived experience of a rheumatic condition were not involved in the design or implementation of this study.</div></div><div><h3>Findings</h3><div>The cohort comprised 5597 individuals; 3944 (70·5%) of 5597 patients were female, 1653 (29·5%) were male, 657 (11·7%) were Black, 224 (4·0%) were Hispanic, and the median age was 63 (50–73) years. 1295 (23·1%) of 5597 individuals lived in the most historically redlined areas (HOLC D) and 1780 (31·8%) lived in areas with the most concentrated present-day racialised economic deprivation (ICE quintile 1). Individuals in historically redlined areas (HOLC D) had greater odds of having four or more missed appointments (odds ratio [OR] 1·78 [95% CI 1·21–2·61]; p=0·0033) and of three or more emergency department visits (2·69 [1·48–4·89]; p=0·0011) compared with those in the most desirable neighbourhoods (HOLC A). Individuals in areas with highly concentrated racial and economic deprivation (ICE quintile 1) had greater odds of four or more missed appointments (OR 2·11 [95% CI 1·65–2·71]; p<0·0001) and of three or more emergency department visits (2·97 [2·02–4·35]; p<0·0001) versus those in areas with highly concentrated privilege (ICE quintile 5).</div></div><div><h3>Interpretation</h3><div>Historical redlining could be a structural determinant of inequities in present-day health-care utilisation patterns. Policy interventions that disma
{"title":"Association of historical redlining and present-day racialised economic segregation with health-care utilisation among individuals with rheumatic conditions in Massachusetts and surrounding areas of the USA: a retrospective cohort study","authors":"Sherry Yang BS , Leah Santacroce MS , Jamie E Collins PhD , Candace H Feldman MD ScD","doi":"10.1016/S2665-9913(24)00235-2","DOIUrl":"10.1016/S2665-9913(24)00235-2","url":null,"abstract":"<div><h3>Background</h3><div>Structural racism lies at the root of inequities; however its impact on rheumatology care is understudied. Redlining was a US federal government-sponsored practice that mapped areas with high concentrations of Black and immigrant residents as hazardous for investment. We aimed to investigate the association of historical redlining and present-day racialised economic segregation, on health-care utilisation among individuals with rheumatic conditions in the US state of Massachusetts and surrounding areas.</div></div><div><h3>Methods</h3><div>This retrospective observational cohort study used multihospital data from the Mass General Brigham Research Patient Data Registry to identify individuals aged ≥ 18 years living in Massachusetts and surrounding areas, with two or more International Classification of Diseases codes for a rheumatic condition. Individuals were included if they received care between Jan 1, 2000, and May 1, 2023, at rheumatology practices affiliated with Mass General Brigham (Boston, MA, USA). Addresses were geocoded and overlaid with 1930s Home Owners' Loan Corporation (HOLC) redlining files. The Index of Concentration at the Extremes (ICE) for combined racial and income polarisation was constructed from US Census data. We used multilevel, multinomial logistic regression models to examine the odds of health-care utilisation separately by historical HOLC grade (A [best] to D [hazardous]) and ICE quintile (most deprived [1] to most privileged [5] race and income), adjusting for demographics, insurance, and comorbidities. People with lived experience of a rheumatic condition were not involved in the design or implementation of this study.</div></div><div><h3>Findings</h3><div>The cohort comprised 5597 individuals; 3944 (70·5%) of 5597 patients were female, 1653 (29·5%) were male, 657 (11·7%) were Black, 224 (4·0%) were Hispanic, and the median age was 63 (50–73) years. 1295 (23·1%) of 5597 individuals lived in the most historically redlined areas (HOLC D) and 1780 (31·8%) lived in areas with the most concentrated present-day racialised economic deprivation (ICE quintile 1). Individuals in historically redlined areas (HOLC D) had greater odds of having four or more missed appointments (odds ratio [OR] 1·78 [95% CI 1·21–2·61]; p=0·0033) and of three or more emergency department visits (2·69 [1·48–4·89]; p=0·0011) compared with those in the most desirable neighbourhoods (HOLC A). Individuals in areas with highly concentrated racial and economic deprivation (ICE quintile 1) had greater odds of four or more missed appointments (OR 2·11 [95% CI 1·65–2·71]; p<0·0001) and of three or more emergency department visits (2·97 [2·02–4·35]; p<0·0001) versus those in areas with highly concentrated privilege (ICE quintile 5).</div></div><div><h3>Interpretation</h3><div>Historical redlining could be a structural determinant of inequities in present-day health-care utilisation patterns. Policy interventions that disma","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 1","pages":"Pages e33-e43"},"PeriodicalIF":15.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693678","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}
Pub Date : 2024-12-20DOI: 10.1016/S2665-9913(24)00336-9
Paul Studenic
{"title":"Heading for remission and its continuation in rheumatoid arthritis.","authors":"Paul Studenic","doi":"10.1016/S2665-9913(24)00336-9","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00336-9","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883382","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}
Pub Date : 2024-12-20DOI: 10.1016/S2665-9913(24)00234-0
Judith W Heutz, Pascal H P de Jong, Marloes Verstappen, Annette H M van der Helm-van Mil, Elise van Mulligen
<p><strong>Background: </strong>About 20% of patients with rheumatoid arthritis on disease-modifying antirheumatic drugs (DMARDs) can reach sustained DMARD-free remission. Nonetheless, the 2022 EULAR recommendations discourage complete cessation of DMARDs due to flare risk. The evidence behind this recommendation is obtained from trial populations using biological DMARDs, representing only a subgroup of the total population of patients with rheumatoid arthritis. We hypothesised that patients requiring biological DMARDs represent a subgroup that is less capable of reaching sustained DMARD-free remission compared with patients not requiring a biological DMARD.</p><p><strong>Methods: </strong>In this study we used data from two prospectively followed up populations of patients with early rheumatoid arthritis, the Leiden Early Arthritis Clinic (EAC) and the treatment in the Rotterdam Early Arthritis Cohort (tREACH), a treat-to-target steered trial in which biological DMARDs were started when patients had inadequate response to triple DMARD-therapy (methotrexate, sulfasalazine, and hydroxychloroquine). Patient partners were involved in the design of both the EAC and tREACH. The primary outcome was sustained DMARD-free remission, which was defined as absence of clinical synovitis after discontinuation of DMARDs for at least 1 year. Patients who did or did not receive biological DMARDs in 5 years (EAC) or 3 years (tREACH) were compared using Kaplan-Meier curves.</p><p><strong>Findings: </strong>627 patients from the EAC were included, of whom 391 (62%) were female and 236 (38%) were male. The mean age was 60 years (SD 14) and 502 (95%) of 529 patients were White. 89 (14%) of 627 patients had ever used a biological DMARD and 538 (86%) had never used a biological DMARD. None of the patients that used a biological DMARD reached sustained DMARD-free remission, whereas 37% of the patients who never used a biological DMARD reached sustained DMARD-free remission at 5 years (hazard ratio [HR] 0·02, 95% CI 0·00-0·10; p<0·0001). From the tREACH population, 425 patients were included in the study. 286 (67%) patients were female, 139 (33%) were male, and the mean age was 54 years (SD 14); ethnicity data not recorded. 154 (36%) of 425 patients had ever used a biological DMARD and 271 (64%) had never used a biological DMARD during follow-up. None of the patients that used a biological DMARD reached sustained DMARD-free remission, whereas 15% of patients who never used a biological DMARD reached sustained DMARD-free remission at 3 years (HR 0·03, 95% CI 0·00-0·21; p<0·0001).</p><p><strong>Interpretation: </strong>For the subgroup of patients with rheumatoid arthritis who require biological DMARDs, sustained DMARD-free remission does not seem attainable. In contrast, in patients with rheumatoid arthritis who do not require biological DMARDs, DMARD-free remission is attainable. These data suggest that the current EULAR recommendation to not stop DMARD use might suffer f
研究背景:大约20%的类风湿关节炎患者使用改善疾病的抗风湿药物(DMARDs)可以达到持续的无dmard缓解。尽管如此,2022年EULAR建议不鼓励完全停止使用dmard,因为有耀斑风险。这一建议背后的证据来自使用生物dmard的试验人群,仅代表类风湿关节炎患者总人群中的一个亚组。我们假设需要生物DMARD的患者代表一个亚组,与不需要生物DMARD的患者相比,他们达到持续无DMARD缓解的能力较差。方法:在这项研究中,我们使用了来自两个前瞻性随访的早期类风湿关节炎患者群体的数据,莱顿早期关节炎诊所(EAC)和鹿特丹早期关节炎队列(tREACH)的治疗,这是一项治疗-靶点导向试验,当患者对三联dmard治疗(甲氨蝶呤,磺胺嘧啶和羟氯喹)反应不足时开始使用生物dmard。患者伴侣参与了EAC和tREACH的设计。主要结局是持续无dmard缓解,定义为停用dmard至少1年后无临床滑膜炎。使用Kaplan-Meier曲线对5年(EAC)或3年(tREACH)接受或未接受生物dmard的患者进行比较。结果:纳入EAC的627例患者,其中391例(62%)为女性,236例(38%)为男性。平均年龄为60岁(SD 14), 529例患者中502例(95%)为白种人,627例患者中89例(14%)曾使用过生物DMARD, 538例(86%)从未使用过生物DMARD。使用生物DMARD的患者均未达到持续无DMARD缓解,而从未使用生物DMARD的患者中有37%在5年时达到持续无DMARD缓解(风险比[HR] 0.02, 95% CI 0.00 - 0.10;结论:对于需要生物dmard的类风湿关节炎患者亚组,持续无dmard缓解似乎无法实现。相比之下,在不需要生物dmard的类风湿性关节炎患者中,可以实现无dmard缓解。这些数据表明,目前EULAR关于不停止使用DMARD的建议可能存在确定偏差。今后关于停用DMARD的建议应加以修订。资助:荷兰关节炎基金会和欧洲研究委员会。
{"title":"Sustained DMARD-free remission in subgroups of patients with rheumatoid arthritis: an analysis of two prospective cohorts with early arthritis.","authors":"Judith W Heutz, Pascal H P de Jong, Marloes Verstappen, Annette H M van der Helm-van Mil, Elise van Mulligen","doi":"10.1016/S2665-9913(24)00234-0","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00234-0","url":null,"abstract":"<p><strong>Background: </strong>About 20% of patients with rheumatoid arthritis on disease-modifying antirheumatic drugs (DMARDs) can reach sustained DMARD-free remission. Nonetheless, the 2022 EULAR recommendations discourage complete cessation of DMARDs due to flare risk. The evidence behind this recommendation is obtained from trial populations using biological DMARDs, representing only a subgroup of the total population of patients with rheumatoid arthritis. We hypothesised that patients requiring biological DMARDs represent a subgroup that is less capable of reaching sustained DMARD-free remission compared with patients not requiring a biological DMARD.</p><p><strong>Methods: </strong>In this study we used data from two prospectively followed up populations of patients with early rheumatoid arthritis, the Leiden Early Arthritis Clinic (EAC) and the treatment in the Rotterdam Early Arthritis Cohort (tREACH), a treat-to-target steered trial in which biological DMARDs were started when patients had inadequate response to triple DMARD-therapy (methotrexate, sulfasalazine, and hydroxychloroquine). Patient partners were involved in the design of both the EAC and tREACH. The primary outcome was sustained DMARD-free remission, which was defined as absence of clinical synovitis after discontinuation of DMARDs for at least 1 year. Patients who did or did not receive biological DMARDs in 5 years (EAC) or 3 years (tREACH) were compared using Kaplan-Meier curves.</p><p><strong>Findings: </strong>627 patients from the EAC were included, of whom 391 (62%) were female and 236 (38%) were male. The mean age was 60 years (SD 14) and 502 (95%) of 529 patients were White. 89 (14%) of 627 patients had ever used a biological DMARD and 538 (86%) had never used a biological DMARD. None of the patients that used a biological DMARD reached sustained DMARD-free remission, whereas 37% of the patients who never used a biological DMARD reached sustained DMARD-free remission at 5 years (hazard ratio [HR] 0·02, 95% CI 0·00-0·10; p<0·0001). From the tREACH population, 425 patients were included in the study. 286 (67%) patients were female, 139 (33%) were male, and the mean age was 54 years (SD 14); ethnicity data not recorded. 154 (36%) of 425 patients had ever used a biological DMARD and 271 (64%) had never used a biological DMARD during follow-up. None of the patients that used a biological DMARD reached sustained DMARD-free remission, whereas 15% of patients who never used a biological DMARD reached sustained DMARD-free remission at 3 years (HR 0·03, 95% CI 0·00-0·21; p<0·0001).</p><p><strong>Interpretation: </strong>For the subgroup of patients with rheumatoid arthritis who require biological DMARDs, sustained DMARD-free remission does not seem attainable. In contrast, in patients with rheumatoid arthritis who do not require biological DMARDs, DMARD-free remission is attainable. These data suggest that the current EULAR recommendation to not stop DMARD use might suffer f","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883388","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}
Pub Date : 2024-12-20DOI: 10.1016/S2665-9913(24)00275-3
Michael G Matt, Daniel Drozdov, Elisabeth Bendstrup, Mia Glerup, Ellen-Margrethe Hauge, Tania Masmas, Elvira Cannizzaro Schneider, Ulrike B Zeilhofer, Rolla F Abu-Arja, Kyla D Driest, Joseph H Oved, Karen Onel, Christen L Ebens, Deepakbabu Chellapandian, Shanmuganathan Chandrakasan, Sampath Prahalad, Johannes Roth, Susan E Prockop, Juliana Silva, Andrew H Schapiro, Christopher Towe, Sharat Chandra, Alexei Grom, Grant S Schulert, Rebecca A Marsh
Background: Systemic juvenile idiopathic arthritis-related lung disease (sJIA-LD) is a severe complication in patients with treatment-refractory systemic juvenile idiopathic arthritis (sJIA). The objective of this study was to evaluate the effect of allogeneic haematopoietic stem-cell transplantation (HSCT) in a cohort of children with sJIA-LD.
Methods: This international, retrospective cohort study was performed in nine hospitals across the USA and Europe in children with sJIA-LD who had received allogeneic HSCT. Patients' medical charts were reviewed and their data extracted using a standardised form. The outcomes assessed were allogeneic HSCT outcomes (eg, engraftment and donor chimerism, and transplant-related complications), pulmonary outcomes (eg, oxygen dependence, chest CT findings, and pulmonary function test results), and overall outcomes (eg, death, complete response, or partial response). A complete response was defined as resolution of signs of sJIA without the need for systemic immunomodulatory therapy, in addition to discontinuation of supplemental oxygen.
Findings: Between Jan 18, 2018, and Oct 17, 2022, 13 patients with sJIA-LD, who were refractory to immunosuppressive treatment and who had received an average of six different treatment agents, underwent allogeneic HSCT. Ten (77%) of 13 patients were female and three (23%) were male. The median age at diagnosis of sJIA-LD was 4·8 years (IQR 2·9-14·8) and the median age at transplantation was 9·0 years (5·0-19·0). Pre-HSCT chest CT revealed characteristic sJIA-LD. Five patients required supplemental oxygen before transplantation. Patients received various reduced toxicity or intensity conditioning regimens. Grafts were from 10/10 HLA-matched (n=6) or 9/10 HLA-mismatched (n=5) unrelated donors, a 7/10 related donor (n=1), and a matched sibling (n=1). All patients engrafted. One patient had secondary graft failure and received a second transplant from a different donor. Post-transplantation complications included acute graft-versus-host disease (n=5), bacteraemia (n=8), cytomegalovirus reactivation (n=6), and post-transplantation macrophage activation syndrome (n=3). Four patients died; two from cytomegalovirus pneumonitis, one from intracranial haemorrhage, and one from progressive sJIA-LD. At a median follow-up of 16 months (IQR 6-24), all nine surviving patients had a complete response, with no active features of sJIA, no biological therapy or corticosteroid use, and no supplemental oxygen dependence.
Interpretation: Allogeneic HSCT might be a valuable treatment option for patients with refractory sJIA and sJIA-LD and should be considered for children with worsening oxygen dependence or severe treatment-related morbidity.
Funding: National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR079525).
{"title":"Allogeneic haematopoietic stem-cell transplantation for children with refractory systemic juvenile idiopathic arthritis and associated lung disease: outcomes from an international, retrospective cohort study.","authors":"Michael G Matt, Daniel Drozdov, Elisabeth Bendstrup, Mia Glerup, Ellen-Margrethe Hauge, Tania Masmas, Elvira Cannizzaro Schneider, Ulrike B Zeilhofer, Rolla F Abu-Arja, Kyla D Driest, Joseph H Oved, Karen Onel, Christen L Ebens, Deepakbabu Chellapandian, Shanmuganathan Chandrakasan, Sampath Prahalad, Johannes Roth, Susan E Prockop, Juliana Silva, Andrew H Schapiro, Christopher Towe, Sharat Chandra, Alexei Grom, Grant S Schulert, Rebecca A Marsh","doi":"10.1016/S2665-9913(24)00275-3","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00275-3","url":null,"abstract":"<p><strong>Background: </strong>Systemic juvenile idiopathic arthritis-related lung disease (sJIA-LD) is a severe complication in patients with treatment-refractory systemic juvenile idiopathic arthritis (sJIA). The objective of this study was to evaluate the effect of allogeneic haematopoietic stem-cell transplantation (HSCT) in a cohort of children with sJIA-LD.</p><p><strong>Methods: </strong>This international, retrospective cohort study was performed in nine hospitals across the USA and Europe in children with sJIA-LD who had received allogeneic HSCT. Patients' medical charts were reviewed and their data extracted using a standardised form. The outcomes assessed were allogeneic HSCT outcomes (eg, engraftment and donor chimerism, and transplant-related complications), pulmonary outcomes (eg, oxygen dependence, chest CT findings, and pulmonary function test results), and overall outcomes (eg, death, complete response, or partial response). A complete response was defined as resolution of signs of sJIA without the need for systemic immunomodulatory therapy, in addition to discontinuation of supplemental oxygen.</p><p><strong>Findings: </strong>Between Jan 18, 2018, and Oct 17, 2022, 13 patients with sJIA-LD, who were refractory to immunosuppressive treatment and who had received an average of six different treatment agents, underwent allogeneic HSCT. Ten (77%) of 13 patients were female and three (23%) were male. The median age at diagnosis of sJIA-LD was 4·8 years (IQR 2·9-14·8) and the median age at transplantation was 9·0 years (5·0-19·0). Pre-HSCT chest CT revealed characteristic sJIA-LD. Five patients required supplemental oxygen before transplantation. Patients received various reduced toxicity or intensity conditioning regimens. Grafts were from 10/10 HLA-matched (n=6) or 9/10 HLA-mismatched (n=5) unrelated donors, a 7/10 related donor (n=1), and a matched sibling (n=1). All patients engrafted. One patient had secondary graft failure and received a second transplant from a different donor. Post-transplantation complications included acute graft-versus-host disease (n=5), bacteraemia (n=8), cytomegalovirus reactivation (n=6), and post-transplantation macrophage activation syndrome (n=3). Four patients died; two from cytomegalovirus pneumonitis, one from intracranial haemorrhage, and one from progressive sJIA-LD. At a median follow-up of 16 months (IQR 6-24), all nine surviving patients had a complete response, with no active features of sJIA, no biological therapy or corticosteroid use, and no supplemental oxygen dependence.</p><p><strong>Interpretation: </strong>Allogeneic HSCT might be a valuable treatment option for patients with refractory sJIA and sJIA-LD and should be considered for children with worsening oxygen dependence or severe treatment-related morbidity.</p><p><strong>Funding: </strong>National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR079525).</p>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883416","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}
Pub Date : 2024-12-18DOI: 10.1016/S2665-9913(24)00248-0
Edoardo Cipolletta, Georgina Nakafero, Natalie McCormick, Chio Yokose, Anthony J Avery, Mamas A Mamas, Hyon K Choi, Laila J Tata, Abhishek Abhishek
<p><strong>Background: </strong>Initiating urate-lowering therapy can trigger gout flares. Gout flares have been associated with a temporally increased risk of cardiovascular events. Therefore, we aimed to estimate the risk of cardiovascular events in patients with gout initiating urate-lowering therapy with flare prophylaxis using colchicine (the drug recommended for gout flare prohphylaxis by many international societies) compared with no prophylaxis.</p><p><strong>Methods: </strong>We did a retrospective new-user cohort study using data from the Clinical Practice Research Datalink Aurum, an English primary-care database linked to hospitalisation and mortality records. People with gout initiating urate-lowering therapy for the first time were eligible for inclusion. We compared people prescribed flare prophylaxis with colchicine with those not prescribed any gout flare prophylaxis. Colchicine prophylaxis (defined as prescription for ≥21 days) prescribed on the same date as urate-lowering therapy was the exposure of interest. A composite of fatal and non-fatal myocardial infarction or stroke within 180 days after urate-lowering therapy initiation regardless of any previous cardiovascular event was the primary outcome. Propensity score overlap weighting was used to balance covariates across study groups. We used Cox regression and performed intention-to-treat and per-protocol analyses, the latter with an inverse probability of censoring weighting. The association was measured using hazard ratio and risk difference with 95% CIs. Members of The UK Gout Society were involved in prioritising the research question.</p><p><strong>Findings: </strong>Of the 111 460 patients eligible for the study, 99 800 patients with gout initiating urate-lowering therapy were included. 25 511 (25·6%) of 99 800 patients were female, 74 289 (74·4%) were male, 84 928 (85·1%) patients were White and the mean age was 62·8 years (SD 15·5). 4063 (4·1%) patients had previous cardiovascular events and 16 028 (16·1%) patients were prescribed colchicine prophylaxis. Patients with colchicine prophylaxis had significantly lower risk of cardiovascular events compared with those without prophylaxis. The weighted rates of cardiovascular events were 28·8 per 1000 person-years (95% CI 25·2 to 33·2) in patients with colchicine prophylaxis and 35·3 per 1000 person-years (33·0 to 37·9) in those without prophylaxis (weighted rate difference -6·5 [95% CI -9·4 to -3·6] per 1000 person-years and weighted hazard ratio 0·82 [0·69-0·94]) in the intention-to-treat analysis. Findings were similar across analytical approaches, stratified analyses, and for secondary outcomes.</p><p><strong>Interpretation: </strong>In patients with gout initiating urate-lowering therapy, the risk of cardiovascular events was reduced in those prescribed colchicine prophylaxis compared with no prophylaxis. These findings provide an additional argument for using colchicine for gout flare prophylaxis.</p><p><strong>Fundin
{"title":"Cardiovascular events in patients with gout initiating urate-lowering therapy with or without colchicine for flare prophylaxis: a retrospective new-user cohort study using linked primary care, hospitalisation, and mortality data.","authors":"Edoardo Cipolletta, Georgina Nakafero, Natalie McCormick, Chio Yokose, Anthony J Avery, Mamas A Mamas, Hyon K Choi, Laila J Tata, Abhishek Abhishek","doi":"10.1016/S2665-9913(24)00248-0","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00248-0","url":null,"abstract":"<p><strong>Background: </strong>Initiating urate-lowering therapy can trigger gout flares. Gout flares have been associated with a temporally increased risk of cardiovascular events. Therefore, we aimed to estimate the risk of cardiovascular events in patients with gout initiating urate-lowering therapy with flare prophylaxis using colchicine (the drug recommended for gout flare prohphylaxis by many international societies) compared with no prophylaxis.</p><p><strong>Methods: </strong>We did a retrospective new-user cohort study using data from the Clinical Practice Research Datalink Aurum, an English primary-care database linked to hospitalisation and mortality records. People with gout initiating urate-lowering therapy for the first time were eligible for inclusion. We compared people prescribed flare prophylaxis with colchicine with those not prescribed any gout flare prophylaxis. Colchicine prophylaxis (defined as prescription for ≥21 days) prescribed on the same date as urate-lowering therapy was the exposure of interest. A composite of fatal and non-fatal myocardial infarction or stroke within 180 days after urate-lowering therapy initiation regardless of any previous cardiovascular event was the primary outcome. Propensity score overlap weighting was used to balance covariates across study groups. We used Cox regression and performed intention-to-treat and per-protocol analyses, the latter with an inverse probability of censoring weighting. The association was measured using hazard ratio and risk difference with 95% CIs. Members of The UK Gout Society were involved in prioritising the research question.</p><p><strong>Findings: </strong>Of the 111 460 patients eligible for the study, 99 800 patients with gout initiating urate-lowering therapy were included. 25 511 (25·6%) of 99 800 patients were female, 74 289 (74·4%) were male, 84 928 (85·1%) patients were White and the mean age was 62·8 years (SD 15·5). 4063 (4·1%) patients had previous cardiovascular events and 16 028 (16·1%) patients were prescribed colchicine prophylaxis. Patients with colchicine prophylaxis had significantly lower risk of cardiovascular events compared with those without prophylaxis. The weighted rates of cardiovascular events were 28·8 per 1000 person-years (95% CI 25·2 to 33·2) in patients with colchicine prophylaxis and 35·3 per 1000 person-years (33·0 to 37·9) in those without prophylaxis (weighted rate difference -6·5 [95% CI -9·4 to -3·6] per 1000 person-years and weighted hazard ratio 0·82 [0·69-0·94]) in the intention-to-treat analysis. Findings were similar across analytical approaches, stratified analyses, and for secondary outcomes.</p><p><strong>Interpretation: </strong>In patients with gout initiating urate-lowering therapy, the risk of cardiovascular events was reduced in those prescribed colchicine prophylaxis compared with no prophylaxis. These findings provide an additional argument for using colchicine for gout flare prophylaxis.</p><p><strong>Fundin","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873239","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}
Pub Date : 2024-12-18DOI: 10.1016/S2665-9913(24)00332-1
Hein Janssens, Matthijs Janssen
{"title":"Beneficial side-effects of colchicine for patients with gout.","authors":"Hein Janssens, Matthijs Janssen","doi":"10.1016/S2665-9913(24)00332-1","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00332-1","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873203","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}
Pub Date : 2024-12-17DOI: 10.1016/S2665-9913(24)00351-5
Ioannis Parodis
{"title":"Promise and challenges of mesenchymal stromal cell therapy in severe SLE.","authors":"Ioannis Parodis","doi":"10.1016/S2665-9913(24)00351-5","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00351-5","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873240","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}
Pub Date : 2024-12-17DOI: 10.1016/S2665-9913(24)00298-4
Dominique Farge, Lucie Biard, Ben Weil, Virginie Girault, Pauline Lansiaux, Ingrid Munia, Séverine Loisel, Catney Charles, Judikael Saout, Matthieu Resche-Rigon, Anne Sophie Korganow, Clément Beuvon, Grégory Pugnet, Carlotta Cacciatore, Noémie Abisror, Jean Luc Taupin, Audrey Cras, Mark W Lowdell, Karin Tarte
<p><strong>Background: </strong>Patients with systemic lupus erythematosus (SLE) with inadequate responses to standard therapies have unmet therapeutic needs. The immunomodulatory, proangiogenic, and antifibrotic properties of mesenchymal stromal cells support their use in treating patients with SLE. We aimed to assess the safety of a single intravenous infusion of allogeneic umbilical cord-derived mesenchymal stromal cells in patients with severe SLE.</p><p><strong>Methods: </strong>This prospective, single-centre, open-label, dose-escalation, Bayesian phase 1 study was done at the Saint-Louis University Hospital (Paris, France). Eligible patients were aged 18-70 years, were diagnosed with SLE according to American College of Rheumatology criteria with positive antinuclear antibodies, had a baseline Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score of 6 or more, and had disease that was refractory to first and second line SLE therapies. Patients were to receive a single intravenous infusion of 1 × 10<sup>6</sup>, 2 × 10<sup>6</sup>, or 4 × 10<sup>6</sup> umbilical cord-derived mesenchymal stromal cells per kg (manufactured from a single umbilical cord) in cohorts of five patients per dose, starting at 2 × 10<sup>6</sup> cells per kg. The primary endpoint was the rate of treatment-related severe adverse events (grade ≥3) in the first 10 days after infusion of umbilical cord-derived mesenchymal stromal cells. People with lived experience were involved in study design, patient enrolment, and dissemination of the study findings. This study is registered with ClinicalTrials.gov, NCT03562065, and the EU Clinical Trials Register, EudraCT2017-001400-29.</p><p><strong>Findings: </strong>From May 14, 2019, to March 6, 2023, 29 patients were screened for eligibility, eight of whom were enrolled in the study. Enrolment was terminated early after inclusion of eight patients and no patients received the 1 × 10<sup>6</sup> dose of umbilical cord-derived mesenchymal stromal cells. Seven (88%) of eight participants were cisgender women and one (13%) was a cisgender man. The median age was 35 years (range 26-57) and the median SLE disease duration was 12 years (5-19). All patients received at least 2 × 10<sup>6</sup> cells per kg (range 2 × 10<sup>6</sup> to 4 × 10<sup>6</sup>). No severe adverse events and three infusion-related adverse events (two grade 1 and one grade 2) occurred in two patients in the first 10 days after infusion. After 12·4 months (range 12-13) of follow-up, no treatment-related severe adverse events and three non-treatment-related severe adverse events occurred in one patient after relapse.</p><p><strong>Interpretation: </strong>Our results suggest that a single infusion of 2 × 10<sup>6</sup> cells per kg or 4 × 10<sup>6</sup> cells per kg of allogeneic umbilical cord-derived mesenchymal stromal cells was safe in patients with severe SLE. Placebo-controlled trials are needed to c
{"title":"Allogeneic umbilical cord-derived mesenchymal stromal cells as treatment for systemic lupus erythematosus: a single-centre, open-label, dose-escalation, phase 1 study.","authors":"Dominique Farge, Lucie Biard, Ben Weil, Virginie Girault, Pauline Lansiaux, Ingrid Munia, Séverine Loisel, Catney Charles, Judikael Saout, Matthieu Resche-Rigon, Anne Sophie Korganow, Clément Beuvon, Grégory Pugnet, Carlotta Cacciatore, Noémie Abisror, Jean Luc Taupin, Audrey Cras, Mark W Lowdell, Karin Tarte","doi":"10.1016/S2665-9913(24)00298-4","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00298-4","url":null,"abstract":"<p><strong>Background: </strong>Patients with systemic lupus erythematosus (SLE) with inadequate responses to standard therapies have unmet therapeutic needs. The immunomodulatory, proangiogenic, and antifibrotic properties of mesenchymal stromal cells support their use in treating patients with SLE. We aimed to assess the safety of a single intravenous infusion of allogeneic umbilical cord-derived mesenchymal stromal cells in patients with severe SLE.</p><p><strong>Methods: </strong>This prospective, single-centre, open-label, dose-escalation, Bayesian phase 1 study was done at the Saint-Louis University Hospital (Paris, France). Eligible patients were aged 18-70 years, were diagnosed with SLE according to American College of Rheumatology criteria with positive antinuclear antibodies, had a baseline Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score of 6 or more, and had disease that was refractory to first and second line SLE therapies. Patients were to receive a single intravenous infusion of 1 × 10<sup>6</sup>, 2 × 10<sup>6</sup>, or 4 × 10<sup>6</sup> umbilical cord-derived mesenchymal stromal cells per kg (manufactured from a single umbilical cord) in cohorts of five patients per dose, starting at 2 × 10<sup>6</sup> cells per kg. The primary endpoint was the rate of treatment-related severe adverse events (grade ≥3) in the first 10 days after infusion of umbilical cord-derived mesenchymal stromal cells. People with lived experience were involved in study design, patient enrolment, and dissemination of the study findings. This study is registered with ClinicalTrials.gov, NCT03562065, and the EU Clinical Trials Register, EudraCT2017-001400-29.</p><p><strong>Findings: </strong>From May 14, 2019, to March 6, 2023, 29 patients were screened for eligibility, eight of whom were enrolled in the study. Enrolment was terminated early after inclusion of eight patients and no patients received the 1 × 10<sup>6</sup> dose of umbilical cord-derived mesenchymal stromal cells. Seven (88%) of eight participants were cisgender women and one (13%) was a cisgender man. The median age was 35 years (range 26-57) and the median SLE disease duration was 12 years (5-19). All patients received at least 2 × 10<sup>6</sup> cells per kg (range 2 × 10<sup>6</sup> to 4 × 10<sup>6</sup>). No severe adverse events and three infusion-related adverse events (two grade 1 and one grade 2) occurred in two patients in the first 10 days after infusion. After 12·4 months (range 12-13) of follow-up, no treatment-related severe adverse events and three non-treatment-related severe adverse events occurred in one patient after relapse.</p><p><strong>Interpretation: </strong>Our results suggest that a single infusion of 2 × 10<sup>6</sup> cells per kg or 4 × 10<sup>6</sup> cells per kg of allogeneic umbilical cord-derived mesenchymal stromal cells was safe in patients with severe SLE. Placebo-controlled trials are needed to c","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873192","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}