Pub Date : 2024-10-11DOI: 10.1016/S2665-9913(24)00223-6
Amanda Malone PhD , Mark M Kowalski MD , James Helliwell MD , Sidsel Lynggaard Boll MD , Helene Rovsing MD , Kathrine Moriat MD , Alejandro Castillo Mondragón MD , Yanqi Li PhD , Claire Prener Miller MD , Asger Reinstrup Bihlet PhD , Christine Dobek MSc , Vik Peck BSc , Mike Wilmink MD , Lee S Simon MD , Prof Philip G Conaghan MBBS
<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT04120402</span><svg><path></path></svg></span>, and the EU Clinical Trials Register, EudraCT 2021-000859-39, and is complete.</div></div><div><h3>Findings</h3><div>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 t
{"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 PhD , Mark M Kowalski MD , James Helliwell MD , Sidsel Lynggaard Boll MD , Helene Rovsing MD , Kathrine Moriat MD , Alejandro Castillo Mondragón MD , Yanqi Li PhD , Claire Prener Miller MD , Asger Reinstrup Bihlet PhD , Christine Dobek MSc , Vik Peck BSc , Mike Wilmink MD , Lee S Simon MD , Prof Philip G Conaghan MBBS","doi":"10.1016/S2665-9913(24)00223-6","DOIUrl":"10.1016/S2665-9913(24)00223-6","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT04120402</span><svg><path></path></svg></span>, and the EU Clinical Trials Register, EudraCT 2021-000859-39, and is complete.</div></div><div><h3>Findings</h3><div>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 t","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 12","pages":"Pages e860-e870"},"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":"OA","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 : 2024-09-24DOI: 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}
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