Pub Date : 2024-11-05DOI: 10.1016/S2665-9913(24)00240-6
Karolina Lungova, Michael Putman
Chimeric antigen receptor (CAR) T cells have recently shown remarkable promise in treating rheumatic diseases, including systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies, and systemic sclerosis. Currently, there are 37 clinical trials registered for CAR T-cell therapy in rheumatic diseases and many more are being planned. Much of this enthusiasm is justifiable, but widespread adoption of CAR T-cell therapy in rheumatology faces several barriers. The trajectory of autoimmune diseases differs from malignancies and a surprisingly narrow population could be eligible for CAR T-cell therapy. Current CAR T-cell approaches rely on B-cell depletion, which has a mixed record of success for many diseases. The high cost of CAR T-cell therapy and potential safety concerns, such as cytokine release syndrome and long-term infection risks, also pose substantial challenges. Moving forward, more targeted CAR T-cell approaches, such as antigen-specific chimeric autoantibody receptors or chimeric autoantigen T-cell receptors, could offer greater efficacy and safety in treating rheumatic diseases.
嵌合抗原受体（CAR）T 细胞最近在治疗风湿性疾病（包括系统性红斑狼疮（SLE）、特发性炎症性肌病和系统性硬化症）方面显示出了显著的前景。目前，已有 37 项 CAR T 细胞疗法在风湿病领域的临床试验注册，还有更多的临床试验正在计划中。这种热情在很大程度上是合理的，但在风湿病学中广泛采用 CAR T 细胞疗法面临着一些障碍。自身免疫性疾病的发展轨迹不同于恶性肿瘤，有资格接受 CAR T 细胞疗法的人群少得惊人。目前的 CAR T 细胞疗法依赖于 B 细胞耗竭，而这种疗法在许多疾病上的成功率参差不齐。CAR T 细胞疗法的高成本和潜在的安全问题，如细胞因子释放综合征和长期感染风险，也构成了巨大的挑战。展望未来，更具针对性的 CAR T 细胞疗法，如抗原特异性嵌合自身抗体受体或嵌合自身抗原 T 细胞受体，可为治疗风湿性疾病提供更高的疗效和安全性。
{"title":"Barriers to CAR T-cell therapy in rheumatology.","authors":"Karolina Lungova, Michael Putman","doi":"10.1016/S2665-9913(24)00240-6","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00240-6","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cells have recently shown remarkable promise in treating rheumatic diseases, including systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies, and systemic sclerosis. Currently, there are 37 clinical trials registered for CAR T-cell therapy in rheumatic diseases and many more are being planned. Much of this enthusiasm is justifiable, but widespread adoption of CAR T-cell therapy in rheumatology faces several barriers. The trajectory of autoimmune diseases differs from malignancies and a surprisingly narrow population could be eligible for CAR T-cell therapy. Current CAR T-cell approaches rely on B-cell depletion, which has a mixed record of success for many diseases. The high cost of CAR T-cell therapy and potential safety concerns, such as cytokine release syndrome and long-term infection risks, also pose substantial challenges. Moving forward, more targeted CAR T-cell approaches, such as antigen-specific chimeric autoantibody receptors or chimeric autoantigen T-cell receptors, could offer greater efficacy and safety in treating rheumatic diseases.</p>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606839","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 : 2024-11-01DOI: 10.1016/S2665-9913(24)00229-7
Kasper Hermans MD , Casper Webers PhD , Prof Annelies Boonen MD , Prof Harald E Vonkeman MD , Prof Astrid van Tubergen MD
<div><h3>Background</h3><div>With rising health-care expenditures and workforce shortages, sustainable alternatives to traditional outpatient follow-up strategies are required to optimise care efficiency. We aimed to investigate the cost-effectiveness and clinical effectiveness of patient-initiated follow-up (PIFU) supported by asynchronous telemedicine for patients with spondyloarthritis compared with usual care in daily practice.</div></div><div><h3>Methods</h3><div>TeleSpA was a multicentre, pragmatic, open-label, randomised controlled trial. Patients with spondyloarthritis and stable disease were randomly assigned (1:1) to either the PIFU and asynchronous telemedicine group or usual care group. All patients received a scheduled outpatient visit at baseline and after 1 year. Patients were monitored remotely at 6 months (PIFU and asynchronous telemedicine) or at the discretion of the treating rheumatologist (usual care). The primary outcome was the number of rheumatology visits within a 1-year period. A trial-based 1-year health-economic evaluation from a Dutch health-care perspective (only including health-care costs) and societal perspective (also including travel costs and work productivity losses), per the Dutch guidelines was used to estimate cost-effectiveness. The safety analysis was done in the intention-to-treat population and was based on spontaneous reports of adverse events and serious adverse events or as observed by the research team. The primary analysis was in the intention-to-treat population. Individuals with relevant lived experience were involved in the study design. This trial was registered with the Dutch National Trial Register (NL71041.068.19) and <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (<span><span>NCT04673825</span><svg><path></path></svg></span>) and is completed.</div></div><div><h3>Findings</h3><div>Between Dec 2, 2020, and June 20, 2022, 200 patients were randomly assigned to PIFU and asynchronous telemedicine (n=100) or usual care (n=100). 79 (40%) of 200 participants were women, 121 (60%) were men, and the mean age was 55·0 years (SD 11·9). After 1 year, the mean number of rheumatology visits was 1·9 (SD 1·5) for the PIFU and asynchronous telemedicine group and 2·6 (1·3) in the usual care group (mean difference –0·7 [95% CI –1·0 to –0·3]; 25·4% reduction; p<0·0001). PIFU and asynchronous telemedicine was cost-effective from a health-care perspective, saving health-care costs (–€180 [95% CI –921 to 560]) without a loss in quality-adjusted life-years (0·004 [95 % CI –0·022 to 0·030]). Seven non-trial-related adverse events occurred in the PIFU and asynchronous telemedicine group and eight in usual care group (including one death).</div></div><div><h3>Interpretation</h3><div>PIFU and asynchronous telemedicine resulted in significant and clinically meaningful reductions in rheumatology visits. This was not at the expense of health outcomes and saved health-care costs.</div></div><div><
{"title":"Patient-initiated follow-up supported by asynchronous telemedicine versus usual care in spondyloarthritis (TeleSpA-study): a randomised controlled trial of clinical and cost-effectiveness","authors":"Kasper Hermans MD , Casper Webers PhD , Prof Annelies Boonen MD , Prof Harald E Vonkeman MD , Prof Astrid van Tubergen MD","doi":"10.1016/S2665-9913(24)00229-7","DOIUrl":"10.1016/S2665-9913(24)00229-7","url":null,"abstract":"<div><h3>Background</h3><div>With rising health-care expenditures and workforce shortages, sustainable alternatives to traditional outpatient follow-up strategies are required to optimise care efficiency. We aimed to investigate the cost-effectiveness and clinical effectiveness of patient-initiated follow-up (PIFU) supported by asynchronous telemedicine for patients with spondyloarthritis compared with usual care in daily practice.</div></div><div><h3>Methods</h3><div>TeleSpA was a multicentre, pragmatic, open-label, randomised controlled trial. Patients with spondyloarthritis and stable disease were randomly assigned (1:1) to either the PIFU and asynchronous telemedicine group or usual care group. All patients received a scheduled outpatient visit at baseline and after 1 year. Patients were monitored remotely at 6 months (PIFU and asynchronous telemedicine) or at the discretion of the treating rheumatologist (usual care). The primary outcome was the number of rheumatology visits within a 1-year period. A trial-based 1-year health-economic evaluation from a Dutch health-care perspective (only including health-care costs) and societal perspective (also including travel costs and work productivity losses), per the Dutch guidelines was used to estimate cost-effectiveness. The safety analysis was done in the intention-to-treat population and was based on spontaneous reports of adverse events and serious adverse events or as observed by the research team. The primary analysis was in the intention-to-treat population. Individuals with relevant lived experience were involved in the study design. This trial was registered with the Dutch National Trial Register (NL71041.068.19) and <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (<span><span>NCT04673825</span><svg><path></path></svg></span>) and is completed.</div></div><div><h3>Findings</h3><div>Between Dec 2, 2020, and June 20, 2022, 200 patients were randomly assigned to PIFU and asynchronous telemedicine (n=100) or usual care (n=100). 79 (40%) of 200 participants were women, 121 (60%) were men, and the mean age was 55·0 years (SD 11·9). After 1 year, the mean number of rheumatology visits was 1·9 (SD 1·5) for the PIFU and asynchronous telemedicine group and 2·6 (1·3) in the usual care group (mean difference –0·7 [95% CI –1·0 to –0·3]; 25·4% reduction; p<0·0001). PIFU and asynchronous telemedicine was cost-effective from a health-care perspective, saving health-care costs (–€180 [95% CI –921 to 560]) without a loss in quality-adjusted life-years (0·004 [95 % CI –0·022 to 0·030]). Seven non-trial-related adverse events occurred in the PIFU and asynchronous telemedicine group and eight in usual care group (including one death).</div></div><div><h3>Interpretation</h3><div>PIFU and asynchronous telemedicine resulted in significant and clinically meaningful reductions in rheumatology visits. This was not at the expense of health outcomes and saved health-care costs.</div></div><div><","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 12","pages":"Pages e848-e859"},"PeriodicalIF":15.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570034","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 : 2024-11-01DOI: 10.1016/S2665-9913(24)00306-0
Sean P Gavan
{"title":"Digital remote monitoring in rheumatology: using health economics to support wider adoption","authors":"Sean P Gavan","doi":"10.1016/S2665-9913(24)00306-0","DOIUrl":"10.1016/S2665-9913(24)00306-0","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 12","pages":"Pages e815-e816"},"PeriodicalIF":15.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570018","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 : 2024-10-22DOI: 10.1016/S2665-9913(24)00237-6
Chao Liang
{"title":"Proximod as a potential therapy for rheumatoid arthritis","authors":"Chao Liang","doi":"10.1016/S2665-9913(24)00237-6","DOIUrl":"10.1016/S2665-9913(24)00237-6","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 12","pages":"Pages e814-e815"},"PeriodicalIF":15.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510632","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 : 2024-10-22DOI: 10.1016/S2665-9913(24)00199-1
Hong Zhang MD , Qianqian Li MSc , Cuiyun Li MSc , Min Wu MSc , Hong Chen MSc , Yang Li MSc , Feng You PhD , Yanshi Zhao BS , Jing Jin PhD , Xiaoguang Chen PhD , Prof Yanhua Ding MD
<div><h3>Background</h3><div>Proximod is a selective agonist of sphingosine-1-phosphate receptor-1 (S1PR1). It acts by redirecting lymphocytes from the circulation to secondary lymph nodes, and is under development as an immunomodulator for rheumatoid arthritis. We aimed to evaluate the safety, pharmacokinetics, and preliminary efficacy of proximod in healthy volunteers and patients with rheumatoid arthritis.</div></div><div><h3>Methods</h3><div>We did a two part, phase 1, double-blind, randomised, placebo-controlled, ascending dose trial at a single centre in China. Eligible participants were adults aged 18–50 years with a BMI of 18–28 kg/m<sup>2</sup> for healthy volunteers and aged 18–70 years with a BMI of 18–30 kg/m<sup>2</sup> for patients with rheumatoid arthritis. In part 1, healthy volunteers were randomly assigned within ten cohorts to receive a single oral dose of proximod (0·125 mg, 0·25 mg, 0·5 mg, 1 mg, 1·5 mg, 2 mg, 3 mg, 5 mg, 10 mg, or 15 mg in cohorts 1–10) or placebo. In part 2, healthy volunteers were randomly assigned to receive once-daily doses of proximod 5 mg or placebo, and patients with rheumatoid arthritis were randomly assigned to receive once-daily doses of proximod 5 mg, proximod 10 mg, or placebo, for 28 days. Patients and investigators were masked to treatment assignment. The primary outcomes were safety, tolerability, and pharmacokinetic profile of proximod for 72 days in healthy volunteers and for 48 days in patients with rhematoid arthritis, assessed in all treated participants. This trial is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (<span><span>NCT06361199</span><svg><path></path></svg></span>, <span><span>NCT06361186</span><svg><path></path></svg></span>), and is complete.</div></div><div><h3>Findings</h3><div>Between Nov 1, 2017, and June 22, 2021, 124 healthy volunteers were randomly assigned in part 1 of the study and 124 were included in the analyses (mean age 34·3 years [SD 6·9], 62 [50%] of 124 participants were women and 62 [50%] were men, and 116 [94%] were Han Chinese ethnicity). Between Feb 16, 2022, and Oct 8, 2023, 113 participants were screened for inclusion in part 2 (80 healthy volunteers and 33 patients with rheumatoid arthritis). 79 participants were excluded and 34 were randomly assigned (10 healthy participants and 24 patients with rheumatoid arthritis), 34 of whom were included in the analyses. Ten (100%) of ten healthy participants were Han Chinese ethnicity, with a mean age of 39·9 years (SD 7·3). Five (50%) of ten healthy volunteers were women and five (50%) were men). 22 (92%) of 24 participants with rheumatoid arthritis were Han Chinese ethnicity, with a mean age of 52·7 years (SD 6·8). 22 (92%) of 24 patients with rheumatoid arthritis were women and two (8%) were men. In part 1, all doses of proximod were well tolerated, with no dose-related adverse reactions or serious adverse events observed. In part 2, 74 adverse reactions were reported i
{"title":"Evaluation of proximod, a selective agonist of sphingosine-1-phosphate receptor-1, in healthy volunteers and patients with rheumatoid arthritis: a phase 1, double-blind, randomised, placebo-controlled, ascending dose trial","authors":"Hong Zhang MD , Qianqian Li MSc , Cuiyun Li MSc , Min Wu MSc , Hong Chen MSc , Yang Li MSc , Feng You PhD , Yanshi Zhao BS , Jing Jin PhD , Xiaoguang Chen PhD , Prof Yanhua Ding MD","doi":"10.1016/S2665-9913(24)00199-1","DOIUrl":"10.1016/S2665-9913(24)00199-1","url":null,"abstract":"<div><h3>Background</h3><div>Proximod is a selective agonist of sphingosine-1-phosphate receptor-1 (S1PR1). It acts by redirecting lymphocytes from the circulation to secondary lymph nodes, and is under development as an immunomodulator for rheumatoid arthritis. We aimed to evaluate the safety, pharmacokinetics, and preliminary efficacy of proximod in healthy volunteers and patients with rheumatoid arthritis.</div></div><div><h3>Methods</h3><div>We did a two part, phase 1, double-blind, randomised, placebo-controlled, ascending dose trial at a single centre in China. Eligible participants were adults aged 18–50 years with a BMI of 18–28 kg/m<sup>2</sup> for healthy volunteers and aged 18–70 years with a BMI of 18–30 kg/m<sup>2</sup> for patients with rheumatoid arthritis. In part 1, healthy volunteers were randomly assigned within ten cohorts to receive a single oral dose of proximod (0·125 mg, 0·25 mg, 0·5 mg, 1 mg, 1·5 mg, 2 mg, 3 mg, 5 mg, 10 mg, or 15 mg in cohorts 1–10) or placebo. In part 2, healthy volunteers were randomly assigned to receive once-daily doses of proximod 5 mg or placebo, and patients with rheumatoid arthritis were randomly assigned to receive once-daily doses of proximod 5 mg, proximod 10 mg, or placebo, for 28 days. Patients and investigators were masked to treatment assignment. The primary outcomes were safety, tolerability, and pharmacokinetic profile of proximod for 72 days in healthy volunteers and for 48 days in patients with rhematoid arthritis, assessed in all treated participants. This trial is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (<span><span>NCT06361199</span><svg><path></path></svg></span>, <span><span>NCT06361186</span><svg><path></path></svg></span>), and is complete.</div></div><div><h3>Findings</h3><div>Between Nov 1, 2017, and June 22, 2021, 124 healthy volunteers were randomly assigned in part 1 of the study and 124 were included in the analyses (mean age 34·3 years [SD 6·9], 62 [50%] of 124 participants were women and 62 [50%] were men, and 116 [94%] were Han Chinese ethnicity). Between Feb 16, 2022, and Oct 8, 2023, 113 participants were screened for inclusion in part 2 (80 healthy volunteers and 33 patients with rheumatoid arthritis). 79 participants were excluded and 34 were randomly assigned (10 healthy participants and 24 patients with rheumatoid arthritis), 34 of whom were included in the analyses. Ten (100%) of ten healthy participants were Han Chinese ethnicity, with a mean age of 39·9 years (SD 7·3). Five (50%) of ten healthy volunteers were women and five (50%) were men). 22 (92%) of 24 participants with rheumatoid arthritis were Han Chinese ethnicity, with a mean age of 52·7 years (SD 6·8). 22 (92%) of 24 patients with rheumatoid arthritis were women and two (8%) were men. In part 1, all doses of proximod were well tolerated, with no dose-related adverse reactions or serious adverse events observed. In part 2, 74 adverse reactions were reported i","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 12","pages":"Pages e837-e847"},"PeriodicalIF":15.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510631","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 : 2024-10-21DOI: 10.1016/S2665-9913(24)00308-4
The Lancet Rheumatology
{"title":"The 2024 US election—voting for equitable health care","authors":"The Lancet Rheumatology","doi":"10.1016/S2665-9913(24)00308-4","DOIUrl":"10.1016/S2665-9913(24)00308-4","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 11","pages":"Page e733"},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510637","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 : 2024-10-21DOI: 10.1016/S2665-9913(24)00281-9
Marita Cross , Kanyin Liane Ong , Hailey Hagins , Ewerton Cousin , Lyn March , Anthony Woolf
{"title":"Gout in central Asia: a few things make a big difference – Authors' reply","authors":"Marita Cross , Kanyin Liane Ong , Hailey Hagins , Ewerton Cousin , Lyn March , Anthony Woolf","doi":"10.1016/S2665-9913(24)00281-9","DOIUrl":"10.1016/S2665-9913(24)00281-9","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 11","pages":"Page e748"},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510635","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 : 2024-10-21DOI: 10.1016/S2665-9913(24)00280-7
Chokan Baimukhamedov , Galymzhan Togizbayev
{"title":"Gout in central Asia: a few things make a big difference","authors":"Chokan Baimukhamedov , Galymzhan Togizbayev","doi":"10.1016/S2665-9913(24)00280-7","DOIUrl":"10.1016/S2665-9913(24)00280-7","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 11","pages":"Pages e747-e748"},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510636","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}
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