Pub Date : 2024-10-11DOI: 10.1016/S2665-9913(24)00223-6
Amanda Malone, Mark M Kowalski, James Helliwell, Sidsel Lynggaard Boll, Helene Rovsing, Kathrine Moriat, Alejandro Castillo Mondragón, Yanqi Li, Claire Prener Miller, Asger Reinstrup Bihlet, Christine Dobek, Vik Peck, Mike Wilmink, Lee S Simon, Philip G Conaghan
<p><strong>Background: </strong>Corticosteroids are among the few effective treatments for knee osteoarthritis, but short duration of action limits their utility. EP-104IAR, a long-acting formulation of fluticasone propionate for intra-articular injection, optimises the action of fluticasone propionate through novel diffusion-based extended-release technology. The SPRINGBOARD trial assessed the efficacy, safety, and pharmacokinetics of EP-104IAR in people with knee osteoarthritis.</p><p><strong>Methods: </strong>SPRINGBOARD was a randomised, vehicle-controlled, double-blind, phase 2 trial done at 12 research sites in Denmark, Poland, and Czech Republic. We recruited adults aged 40 years or older with primary knee osteoarthritis (Kellgren-Lawrence grade 2-3) who reported Western Ontario and McMaster Universities Osteoarthritis Arthritis Index (WOMAC) pain scores of at least 4 and no more than 9 out of 10. Participants were randomly assigned (1:1) to receive one intra-articular dose of 25 mg EP-104IAR or vehicle control. Randomisation was done via interactive web-based access to a central predefined computer-generated list with block size of six (allocated by clinical site). Participants and assessors were masked to treatment allocation. Participants were followed up for 24 weeks. The primary outcome was the difference between groups in change in WOMAC pain score from baseline to week 12, analysed in all participants who were randomly assigned and received treatment. Safety, including laboratory analyses, and pharmacokinetics from quantification of fluticasone propionate in peripheral blood were assessed in all participants who received a dose of randomly assigned treatment. A person with lived experience of knee osteoarthritis was involved in study interpretation and writing of the report. This trial is registered with ClinicalTrials.gov, NCT04120402, and the EU Clinical Trials Register, EudraCT 2021-000859-39, and is complete.</p><p><strong>Findings: </strong>Between Sept 10, 2021, and Nov 16, 2022, 1294 people were screened for eligibility, and 319 were randomly assigned to EP-104IAR (n=164) or vehicle control (n=155). One participant in the EP-104IAR group was excluded from all analyses because treatment was not administered due to an adverse event. 318 participants (135 [42%] male and 183 [58%] female, 315 [99%] White) received randomly assigned treatment and were included in the primary analysis and safety analysis (EP-104IAR, n=163; vehicle control, n=155). At week 12, least squares mean change in WOMAC pain score from baseline was -2·89 (95% CI -3·22 to -2·56) in the EP-104IAR group and -2·23 (-2·56 to -1·89) in the vehicle control group, with a between-group difference of -0·66 (-1·11 to -0·21; p=0·0044); a significant between-group difference persisted to week 14. 106 (65%) of 163 participants in the EP-104IAR group had one or more treatment-emergent adverse event compared with 89 (57%) of 155 participants in the vehicle control group. Ef
{"title":"Efficacy and safety of a diffusion-based extended-release fluticasone propionate intra-articular injection (EP-104IAR) in knee osteoarthritis (SPRINGBOARD): a 24-week, multicentre, randomised, double-blind, vehicle-controlled, phase 2 trial.","authors":"Amanda Malone, Mark M Kowalski, James Helliwell, Sidsel Lynggaard Boll, Helene Rovsing, Kathrine Moriat, Alejandro Castillo Mondragón, Yanqi Li, Claire Prener Miller, Asger Reinstrup Bihlet, Christine Dobek, Vik Peck, Mike Wilmink, Lee S Simon, Philip G Conaghan","doi":"10.1016/S2665-9913(24)00223-6","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00223-6","url":null,"abstract":"<p><strong>Background: </strong>Corticosteroids are among the few effective treatments for knee osteoarthritis, but short duration of action limits their utility. EP-104IAR, a long-acting formulation of fluticasone propionate for intra-articular injection, optimises the action of fluticasone propionate through novel diffusion-based extended-release technology. The SPRINGBOARD trial assessed the efficacy, safety, and pharmacokinetics of EP-104IAR in people with knee osteoarthritis.</p><p><strong>Methods: </strong>SPRINGBOARD was a randomised, vehicle-controlled, double-blind, phase 2 trial done at 12 research sites in Denmark, Poland, and Czech Republic. We recruited adults aged 40 years or older with primary knee osteoarthritis (Kellgren-Lawrence grade 2-3) who reported Western Ontario and McMaster Universities Osteoarthritis Arthritis Index (WOMAC) pain scores of at least 4 and no more than 9 out of 10. Participants were randomly assigned (1:1) to receive one intra-articular dose of 25 mg EP-104IAR or vehicle control. Randomisation was done via interactive web-based access to a central predefined computer-generated list with block size of six (allocated by clinical site). Participants and assessors were masked to treatment allocation. Participants were followed up for 24 weeks. The primary outcome was the difference between groups in change in WOMAC pain score from baseline to week 12, analysed in all participants who were randomly assigned and received treatment. Safety, including laboratory analyses, and pharmacokinetics from quantification of fluticasone propionate in peripheral blood were assessed in all participants who received a dose of randomly assigned treatment. A person with lived experience of knee osteoarthritis was involved in study interpretation and writing of the report. This trial is registered with ClinicalTrials.gov, NCT04120402, and the EU Clinical Trials Register, EudraCT 2021-000859-39, and is complete.</p><p><strong>Findings: </strong>Between Sept 10, 2021, and Nov 16, 2022, 1294 people were screened for eligibility, and 319 were randomly assigned to EP-104IAR (n=164) or vehicle control (n=155). One participant in the EP-104IAR group was excluded from all analyses because treatment was not administered due to an adverse event. 318 participants (135 [42%] male and 183 [58%] female, 315 [99%] White) received randomly assigned treatment and were included in the primary analysis and safety analysis (EP-104IAR, n=163; vehicle control, n=155). At week 12, least squares mean change in WOMAC pain score from baseline was -2·89 (95% CI -3·22 to -2·56) in the EP-104IAR group and -2·23 (-2·56 to -1·89) in the vehicle control group, with a between-group difference of -0·66 (-1·11 to -0·21; p=0·0044); a significant between-group difference persisted to week 14. 106 (65%) of 163 participants in the EP-104IAR group had one or more treatment-emergent adverse event compared with 89 (57%) of 155 participants in the vehicle control group. Ef","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478080","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 : 2024-10-03DOI: 10.1016/S2665-9913(24)00276-5
Xiaoyan Chen , Huifeng Shi , Barbara Wilkinson , Yuanfang Zhu
{"title":"Inclusion of pregnant populations in clinical trials in China: the ethical considerations","authors":"Xiaoyan Chen , Huifeng Shi , Barbara Wilkinson , Yuanfang Zhu","doi":"10.1016/S2665-9913(24)00276-5","DOIUrl":"10.1016/S2665-9913(24)00276-5","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 11","pages":"Pages e746-e747"},"PeriodicalIF":15.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382044","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 : 2024-10-01DOI: 10.1016/S2665-9913(24)00271-6
Ameenat Lola Solebo , Salomey Kellett
{"title":"Inclusive study design to better serve the needs of children and young people with rheumatological conditions","authors":"Ameenat Lola Solebo , Salomey Kellett","doi":"10.1016/S2665-9913(24)00271-6","DOIUrl":"10.1016/S2665-9913(24)00271-6","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 11","pages":"Page e746"},"PeriodicalIF":15.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376156","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 : 2024-09-25DOI: 10.1016/S2665-9913(24)00227-3
Elizabeth Nettleton, Kylie Carlson, Michael Putman
Overdiagnosis occurs when patients are diagnosed with a disease that would otherwise never have affected the quality or duration of their lives. This often happens unintentionally through well-meaning screening programmes that aim to detect diseases during so-called subclinical stages. Recently, it has been suggested that patients with polymyalgia rheumatica should be screened for giant cell arteritis to identify those at higher risk of relapse or vascular complications. Screening for interstitial lung disease for patients with rheumatoid arthritis has also been recommended to identify patients who could benefit from pulmonary interventions. These potential benefits must be weighed against foreseeable harms. Such harms include the uncovering of incidental findings that necessitate additional medical follow-up, the financial costs associated with screening initiatives, the risk of overtreatment through increased immunosuppression in patients who might not have otherwise required it, and the psychosocial burden of a new diagnosis. Randomised clinical trials and prospective cohort studies of screening interventions should be conducted to establish the risks and benefits and identify patients most likely to benefit from them. This Viewpoint covers risks that overdiagnosis presents to the field of rheumatology, with focus on rheumatoid arthritis and polymyalgia rheumatica.
{"title":"The emerging risk of overdiagnosis in rheumatoid arthritis and polymyalgia rheumatica.","authors":"Elizabeth Nettleton, Kylie Carlson, Michael Putman","doi":"10.1016/S2665-9913(24)00227-3","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00227-3","url":null,"abstract":"<p><p>Overdiagnosis occurs when patients are diagnosed with a disease that would otherwise never have affected the quality or duration of their lives. This often happens unintentionally through well-meaning screening programmes that aim to detect diseases during so-called subclinical stages. Recently, it has been suggested that patients with polymyalgia rheumatica should be screened for giant cell arteritis to identify those at higher risk of relapse or vascular complications. Screening for interstitial lung disease for patients with rheumatoid arthritis has also been recommended to identify patients who could benefit from pulmonary interventions. These potential benefits must be weighed against foreseeable harms. Such harms include the uncovering of incidental findings that necessitate additional medical follow-up, the financial costs associated with screening initiatives, the risk of overtreatment through increased immunosuppression in patients who might not have otherwise required it, and the psychosocial burden of a new diagnosis. Randomised clinical trials and prospective cohort studies of screening interventions should be conducted to establish the risks and benefits and identify patients most likely to benefit from them. This Viewpoint covers risks that overdiagnosis presents to the field of rheumatology, with focus on rheumatoid arthritis and polymyalgia rheumatica.</p>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356154","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 : 2024-09-24DOI: 10.1016/S2665-9913(24)00274-1
Elizabeth R Volkmann , John Varga , Bruce R Blazar , Steven Z Pavletic
{"title":"Challenges and solutions for cellular therapy development in autoimmune diseases","authors":"Elizabeth R Volkmann , John Varga , Bruce R Blazar , Steven Z Pavletic","doi":"10.1016/S2665-9913(24)00274-1","DOIUrl":"10.1016/S2665-9913(24)00274-1","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 11","pages":"Pages e740-e743"},"PeriodicalIF":15.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356151","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 : 2024-09-23DOI: 10.1016/S2665-9913(24)00279-0
The Lancet Rheumatology
{"title":"Trials and tribulations for children with rheumatic diseases","authors":"The Lancet Rheumatology","doi":"10.1016/S2665-9913(24)00279-0","DOIUrl":"10.1016/S2665-9913(24)00279-0","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 10","pages":"Page e653"},"PeriodicalIF":15.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310570","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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