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}
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}
Pub Date : 2024-09-18DOI: 10.1016/S2665-9913(24)00193-0
Sebastian E Sattui MD , Bohang Jiang MPH , Xiaoqing Fu MS , Claire Cook MPH , Shruthi Srivatsan BS , Zachary K Williams BS , Guy Katz MD , Prof Yuqing Zhang DSc , Zachary S Wallace MD
<div><h3>Background</h3><div>Frailty, a measure of biological age, might predict poor outcomes in older adults better than chronological age. We aimed to compare the effect of age and frailty on end-stage renal disease, death, and severe infection within 2 years of diagnosis in older adults with incident antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included individuals aged 65 years or older from the Mass General Brigham ANCA-associated vasculitis cohort in the USA who were treated between Jan 1, 2002, and Dec 31, 2019. Individuals with a diagnosis of eosinophilic granulomatosis with polyangiitis were excluded from the analysis. Baseline frailty was measured with a claims-based frailty index using data collected in the year before the date of treatment initiation in individuals with at least one health-care encounter before baseline; individuals who did not have an encounter within the 12 months before baseline were classified as pre-frail. Incidence rates of end-stage renal disease or death and severe infections (ie, infections leading to hospital admission or death) at 2 years were estimated, and multivariable analyses were performed to compare the association of age and frailty with these outcomes. Cumulative incidence rates and an additive interaction analysis were used to assess the interaction of age and frailty groupings.</div></div><div><h3>Findings</h3><div>Of the 234 individuals included, 136 (58%) were women, 98 (42%) were men, 198 (85%) were White, and 198 (85%) were positive for myeloperoxidase-specific ANCA. Frailty was present in 25 (22%) of 116 individuals aged 65–74 years and 44 (37%) of 118 aged 75 years or older. In the multivariable analysis, an age of 75 years or older was associated with an increased risk of end-stage renal disease or death (hazard ratio [HR] 4·50 [95% CI 1·83–11·09]), however, frailty was not (1·08 [0·50–2·36]). Both an age of 75 years or older (HR 2·52 [95% CI 1·26–5·04]) and frailty (8·46 [3·95–18·14]) were independent risk factors for severe infections. The effect of frailty on the incidence of end-stage renal disease or death was greater in individuals aged 65–74 years (frail <em>vs</em> non-frail or pre-frail incidence rate 7·5 cases <em>vs</em> 2·0 cases per 100 person-years) than in those aged 75 years or older (13·5 cases <em>vs</em> 16·0 cases per 100 person-years). The effect of frailty on the incidence of serious infections varied by age, with large differences observed among both individuals aged 65–74 years (frail <em>vs</em> non-frail or pre-frail incidence rate 38·9 cases <em>vs</em> 0·8 cases per 100 person-years) and individuals aged 75 years or older (61·9 cases <em>vs</em> 12·3 cases per 100 person-years). Despite the observed differences between the age groups, the additive interaction terms were not statistically significant for either frailty and end-stage renal disease or death (p for interaction
{"title":"The effects of age and frailty on the risks of end-stage renal disease, death, and severe infection in older adults with antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study","authors":"Sebastian E Sattui MD , Bohang Jiang MPH , Xiaoqing Fu MS , Claire Cook MPH , Shruthi Srivatsan BS , Zachary K Williams BS , Guy Katz MD , Prof Yuqing Zhang DSc , Zachary S Wallace MD","doi":"10.1016/S2665-9913(24)00193-0","DOIUrl":"10.1016/S2665-9913(24)00193-0","url":null,"abstract":"<div><h3>Background</h3><div>Frailty, a measure of biological age, might predict poor outcomes in older adults better than chronological age. We aimed to compare the effect of age and frailty on end-stage renal disease, death, and severe infection within 2 years of diagnosis in older adults with incident antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included individuals aged 65 years or older from the Mass General Brigham ANCA-associated vasculitis cohort in the USA who were treated between Jan 1, 2002, and Dec 31, 2019. Individuals with a diagnosis of eosinophilic granulomatosis with polyangiitis were excluded from the analysis. Baseline frailty was measured with a claims-based frailty index using data collected in the year before the date of treatment initiation in individuals with at least one health-care encounter before baseline; individuals who did not have an encounter within the 12 months before baseline were classified as pre-frail. Incidence rates of end-stage renal disease or death and severe infections (ie, infections leading to hospital admission or death) at 2 years were estimated, and multivariable analyses were performed to compare the association of age and frailty with these outcomes. Cumulative incidence rates and an additive interaction analysis were used to assess the interaction of age and frailty groupings.</div></div><div><h3>Findings</h3><div>Of the 234 individuals included, 136 (58%) were women, 98 (42%) were men, 198 (85%) were White, and 198 (85%) were positive for myeloperoxidase-specific ANCA. Frailty was present in 25 (22%) of 116 individuals aged 65–74 years and 44 (37%) of 118 aged 75 years or older. In the multivariable analysis, an age of 75 years or older was associated with an increased risk of end-stage renal disease or death (hazard ratio [HR] 4·50 [95% CI 1·83–11·09]), however, frailty was not (1·08 [0·50–2·36]). Both an age of 75 years or older (HR 2·52 [95% CI 1·26–5·04]) and frailty (8·46 [3·95–18·14]) were independent risk factors for severe infections. The effect of frailty on the incidence of end-stage renal disease or death was greater in individuals aged 65–74 years (frail <em>vs</em> non-frail or pre-frail incidence rate 7·5 cases <em>vs</em> 2·0 cases per 100 person-years) than in those aged 75 years or older (13·5 cases <em>vs</em> 16·0 cases per 100 person-years). The effect of frailty on the incidence of serious infections varied by age, with large differences observed among both individuals aged 65–74 years (frail <em>vs</em> non-frail or pre-frail incidence rate 38·9 cases <em>vs</em> 0·8 cases per 100 person-years) and individuals aged 75 years or older (61·9 cases <em>vs</em> 12·3 cases per 100 person-years). Despite the observed differences between the age groups, the additive interaction terms were not statistically significant for either frailty and end-stage renal disease or death (p for interaction","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 11","pages":"Pages e771-e779"},"PeriodicalIF":15.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298937","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}