Pub Date : 2024-10-30DOI: 10.1016/S2665-9913(24)00229-7
Kasper Hermans, Casper Webers, Annelies Boonen, Harald E Vonkeman, Astrid van Tubergen
Background: 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.
Methods: 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 ClinicalTrials.gov (NCT04673825) and is completed.
Findings: 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).
Interpretation: 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.
{"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, Casper Webers, Annelies Boonen, Harald E Vonkeman, Astrid van Tubergen","doi":"10.1016/S2665-9913(24)00229-7","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00229-7","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 ClinicalTrials.gov (NCT04673825) and is completed.</p><p><strong>Findings: </strong>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).</p><p><strong>Interpretation: </strong>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.</p><p><strong>Funding: </strong>Dutch Arthritis Society.</p>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-30","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 : 2024-10-30DOI: 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":"https://doi.org/10.1016/S2665-9913(24)00306-0","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-30","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 : 2024-10-30DOI: 10.1016/S2665-9913(24)00232-7
Mikkel Østergaard, Mikael Boesen, Walter P Maksymowych, Robert G Lambert, Michael R Bubb, Olga Kubassova, Guillermo Valenzuela, Jyotsna Reddy, Stephen Colgan, Yuri Klyachkin, Cynthia Deignan, Zhenwei Zhou, Hamid Amouzadeh, Philip J Mease
<p><strong>Background: </strong>The Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS) and MRI Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) have not been used together to assess treatment of psoriatic arthritis in a clinical trial. We aimed to assess the effect of apremilast treatment on inflammation, with outcomes measured by PsAMRIS and MRI-WIPE.</p><p><strong>Methods: </strong>MOSAIC was a phase 4, multicentre, single-arm, open-label study conducted at 29 sites across ten countries (Belgium, Canada, Denmark, Germany, Italy, Russia, Spain, Switzerland, the UK, and the USA). Adults aged 18 years or older with a documented diagnosis of psoriatic arthritis for a duration of 3 months to 5 years self-enrolled and were included if they met the classification criteria for active psoriatic arthritis at screening. Patients were required to have at least three swollen and three tender joints with hand involvement and at least one active enthesitis site according to the Spondyloarthritis Research Consortium of Canada enthesitis index or the Leeds enthesitis index. Patients were excluded if they had previous treatment with a biological disease-modifying antirheumatic drug or previous treatment with more than two conventional synthetic disease-modifying antirheumatic drugs. After a 5-day titration period, patients received apremilast 30 mg orally twice per day. Concomitant stable methotrexate up to 25 mg per week was permitted. The primary endpoint was change from baseline to week 24 in a composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis in the hand as assessed by PsAMRIS. The full analysis set and safety population included all enrolled patients who received at least one dose of apremilast. This completed study is registered with ClinicalTrials.gov (NCT03783026).</p><p><strong>Findings: </strong>Between Feb 6, 2019, and May 11, 2022, 123 patients were enrolled in the MOSAIC study. Of these 123 patients, 122 (99%) were treated with apremilast and included in the full analysis set and safety population. 67 (55%) of 122 patients were female, 55 (45%) were male, and 116 (95%) were White. 80 (66%) of 122 patients completed 48 weeks of treatment. The least squares mean change from baseline to week 24 in the composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis as assessed by PsAMRIS was -2·32 (95% CI -4·73 to 0·09). 95 (78%) of 122 patients had at least one treatment-emergent adverse event. Six (5%) patients had a severe treatment-emergent adverse event and six (5%) patients had a serious treatment-emergent adverse event. No serious treatment-emergent adverse events were considered to be related to apremilast.</p><p><strong>Interpretation: </strong>Apremilast improved inflammation in joints and entheses on assessment of MRI measures in the hand and the whole body. Our findings encourage the use of MRI, including whol
背景：银屑病关节炎磁共振成像评分系统（PsAMRIS银屑病关节炎磁共振成像评分系统（PsAMRIS）和炎症性关节炎外周关节和内膜炎症核磁共振成像全身评分系统（MRI-WIPE）尚未在临床试验中同时用于评估银屑病关节炎的治疗。我们旨在通过PsAMRIS和MRI-WIPE测量结果，评估阿普司特治疗对炎症的影响：MOSAIC是一项4期、多中心、单臂、开放标签研究，在10个国家（比利时、加拿大、丹麦、德国、意大利、俄罗斯、西班牙、瑞士、英国和美国）的29个地点进行。年龄在18岁或18岁以上、被确诊患有银屑病关节炎3个月至5年的成人自行报名参加，如果他们在筛查时符合活动性银屑病关节炎的分类标准，则被纳入研究范围。根据加拿大脊柱关节炎研究联合会（Spondyloarthritis Research Consortium of Canada）的关节炎指数或利兹关节炎指数，患者必须至少有三个关节肿胀和三个关节触痛，且手部受累，并至少有一个活动性关节炎部位。如果患者曾接受过生物改善病情抗风湿药物治疗，或曾接受过两种以上传统合成改善病情抗风湿药物治疗，则排除在外。经过 5 天的滴定期后，患者开始口服阿普司特 30 毫克，每天两次。允许同时服用稳定的甲氨蝶呤，每周不超过25毫克。主要终点是PsAMRIS评估的手部骨髓水肿、滑膜炎和腱鞘炎综合炎症评分从基线到第24周的变化。完整的分析集和安全性人群包括所有接受了至少一次阿普司特治疗的入组患者。这项已完成的研究已在ClinicalTrials.gov（NCT03783026）上注册：2019年2月6日至2022年5月11日期间，MOSAIC研究共招募了123名患者。在这123名患者中，有122人（99%）接受了阿普司特治疗，并纳入了完整的分析集和安全人群。122名患者中有67名（55%）为女性，55名（45%）为男性，116名（95%）为白人。122名患者中有80名（66%）完成了48周的治疗。PsAMRIS评估的骨髓水肿、滑膜炎和腱鞘炎综合炎症评分从基线到第24周的最小二乘法平均变化为-2-32（95% CI -4-73至0-09）。122 名患者中有 95 人（78%）至少出现过一次治疗突发不良事件。6名患者（5%）发生了严重的治疗突发不良事件，6名患者（5%）发生了严重的治疗突发不良事件。没有严重治疗突发不良事件被认为与阿普司特有关：阿普瑞米司特改善了手部和全身核磁共振成像评估中关节和内膜的炎症。我们的研究结果鼓励将核磁共振成像（包括全身核磁共振成像）作为银屑病关节炎患者试验的客观结果测量指标：安进公司。
{"title":"Effect of apremilast on hand and whole-body MRI assessments of inflammation in patients with psoriatic arthritis (MOSAIC): a phase 4, multicentre, single-arm, open-label study.","authors":"Mikkel Østergaard, Mikael Boesen, Walter P Maksymowych, Robert G Lambert, Michael R Bubb, Olga Kubassova, Guillermo Valenzuela, Jyotsna Reddy, Stephen Colgan, Yuri Klyachkin, Cynthia Deignan, Zhenwei Zhou, Hamid Amouzadeh, Philip J Mease","doi":"10.1016/S2665-9913(24)00232-7","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00232-7","url":null,"abstract":"<p><strong>Background: </strong>The Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS) and MRI Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) have not been used together to assess treatment of psoriatic arthritis in a clinical trial. We aimed to assess the effect of apremilast treatment on inflammation, with outcomes measured by PsAMRIS and MRI-WIPE.</p><p><strong>Methods: </strong>MOSAIC was a phase 4, multicentre, single-arm, open-label study conducted at 29 sites across ten countries (Belgium, Canada, Denmark, Germany, Italy, Russia, Spain, Switzerland, the UK, and the USA). Adults aged 18 years or older with a documented diagnosis of psoriatic arthritis for a duration of 3 months to 5 years self-enrolled and were included if they met the classification criteria for active psoriatic arthritis at screening. Patients were required to have at least three swollen and three tender joints with hand involvement and at least one active enthesitis site according to the Spondyloarthritis Research Consortium of Canada enthesitis index or the Leeds enthesitis index. Patients were excluded if they had previous treatment with a biological disease-modifying antirheumatic drug or previous treatment with more than two conventional synthetic disease-modifying antirheumatic drugs. After a 5-day titration period, patients received apremilast 30 mg orally twice per day. Concomitant stable methotrexate up to 25 mg per week was permitted. The primary endpoint was change from baseline to week 24 in a composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis in the hand as assessed by PsAMRIS. The full analysis set and safety population included all enrolled patients who received at least one dose of apremilast. This completed study is registered with ClinicalTrials.gov (NCT03783026).</p><p><strong>Findings: </strong>Between Feb 6, 2019, and May 11, 2022, 123 patients were enrolled in the MOSAIC study. Of these 123 patients, 122 (99%) were treated with apremilast and included in the full analysis set and safety population. 67 (55%) of 122 patients were female, 55 (45%) were male, and 116 (95%) were White. 80 (66%) of 122 patients completed 48 weeks of treatment. The least squares mean change from baseline to week 24 in the composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis as assessed by PsAMRIS was -2·32 (95% CI -4·73 to 0·09). 95 (78%) of 122 patients had at least one treatment-emergent adverse event. Six (5%) patients had a severe treatment-emergent adverse event and six (5%) patients had a serious treatment-emergent adverse event. No serious treatment-emergent adverse events were considered to be related to apremilast.</p><p><strong>Interpretation: </strong>Apremilast improved inflammation in joints and entheses on assessment of MRI measures in the hand and the whole body. Our findings encourage the use of MRI, including whol","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564720","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 : 2024-10-29DOI: 10.1016/S2665-9913(24)00192-9
Emanuel Della-Torre, Rosaria Talarico, Jose Ballarin, Emanuele Bozzalla-Cassione, Chiara Cardamone, Cosimo Cigolini, Francesco Ferro, Tomas Fonseca, George E Fragoulis, Ilaria Galetti, Maria Gerosa, José Hernández-Rodríguez, Marco Lanzillotta, Diana Marinello, Thierry Martin, Fernando Martinez-Valle, Maria Maślińska, Michele Moretti, Marta Mosca, Ulf Müller-Ladner, Cecilia Nalli, Giovanni Orsolini, Cristina Pamfil, Guillermo Perez-Garcia, Roberta Priori, Giacomo Quattrocchio, Andreas Ramming, Francesca Regola, Vasco C Romão, Augusto Silva, Jan A M van Laar, Maria Jose Vicente-Edo, Shlomo Vinker, Tobias Alexander
IgG4-related disease is a rare fibroinflammatory condition. Prompt recognition is fundamental to initiate treatment and to prevent organ damage. Diagnostic and classification criteria are primarily intended for use by clinicians with established expertise in IgG4-related disease. Absence of disease awareness among primary care physicians and specialists without expertise in IgG4-related disease remains the main cause of diagnostic delay. We aimed to identify red flags that might increase the suspicion of IgG4-related disease in primary and secondary care settings. A task force of experts in IgG4-related disease from the European Reference Network for Rare Connective Tissue Diseases (ERN-ReCONNET), patient representatives, and primary care physicians derived potential red flags for IgG4-related disease through a systematic literature search and a level of agreement exercise. Five red flags reached 100% agreement among experts: swelling in one or more organ system; pancreatic and biliary tree involvement; increased serum IgG4; IgG4+ plasma cell tissue infiltration; and obliterative phlebitis. Red flags for IgG4-related disease are intended for use in primary and secondary care to improve referral to centres of expertise and prompt early diagnosis.
{"title":"Identification of red flags for IgG4-related disease: an international European Reference Network for Rare Connective Tissue Diseases framework.","authors":"Emanuel Della-Torre, Rosaria Talarico, Jose Ballarin, Emanuele Bozzalla-Cassione, Chiara Cardamone, Cosimo Cigolini, Francesco Ferro, Tomas Fonseca, George E Fragoulis, Ilaria Galetti, Maria Gerosa, José Hernández-Rodríguez, Marco Lanzillotta, Diana Marinello, Thierry Martin, Fernando Martinez-Valle, Maria Maślińska, Michele Moretti, Marta Mosca, Ulf Müller-Ladner, Cecilia Nalli, Giovanni Orsolini, Cristina Pamfil, Guillermo Perez-Garcia, Roberta Priori, Giacomo Quattrocchio, Andreas Ramming, Francesca Regola, Vasco C Romão, Augusto Silva, Jan A M van Laar, Maria Jose Vicente-Edo, Shlomo Vinker, Tobias Alexander","doi":"10.1016/S2665-9913(24)00192-9","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00192-9","url":null,"abstract":"<p><p>IgG4-related disease is a rare fibroinflammatory condition. Prompt recognition is fundamental to initiate treatment and to prevent organ damage. Diagnostic and classification criteria are primarily intended for use by clinicians with established expertise in IgG4-related disease. Absence of disease awareness among primary care physicians and specialists without expertise in IgG4-related disease remains the main cause of diagnostic delay. We aimed to identify red flags that might increase the suspicion of IgG4-related disease in primary and secondary care settings. A task force of experts in IgG4-related disease from the European Reference Network for Rare Connective Tissue Diseases (ERN-ReCONNET), patient representatives, and primary care physicians derived potential red flags for IgG4-related disease through a systematic literature search and a level of agreement exercise. Five red flags reached 100% agreement among experts: swelling in one or more organ system; pancreatic and biliary tree involvement; increased serum IgG4; IgG4<sup>+</sup> plasma cell tissue infiltration; and obliterative phlebitis. Red flags for IgG4-related disease are intended for use in primary and secondary care to improve referral to centres of expertise and prompt early diagnosis.</p>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564656","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":"https://doi.org/10.1016/S2665-9913(24)00237-6","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"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, Qianqian Li, Cuiyun Li, Min Wu, Hong Chen, Yang Li, Feng You, Yanshi Zhao, Jing Jin, Xiaoguang Chen, Yanhua Ding
<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 ClinicalTrials.gov (NCT06361199, NCT06361186), and is complete.</p><p><strong>Findings: </strong>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 in eight (80%) of ten healthy volunteers and 22 (92%) of 24 patients with rheumatoid arthritis. Adverse events associated with proximod were predominantly mil
{"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, Qianqian Li, Cuiyun Li, Min Wu, Hong Chen, Yang Li, Feng You, Yanshi Zhao, Jing Jin, Xiaoguang Chen, Yanhua Ding","doi":"10.1016/S2665-9913(24)00199-1","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00199-1","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 ClinicalTrials.gov (NCT06361199, NCT06361186), and is complete.</p><p><strong>Findings: </strong>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 in eight (80%) of ten healthy volunteers and 22 (92%) of 24 patients with rheumatoid arthritis. Adverse events associated with proximod were predominantly mil","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"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
{"title":"The 2024 US election—voting for equitable health care","authors":"","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":null,"pages":null},"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
{"title":"Gout in central Asia: a few things make a big difference – Authors' reply","authors":"","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":null,"pages":null},"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
{"title":"Gout in central Asia: a few things make a big difference","authors":"","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":null,"pages":null},"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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