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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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)00220-0
Alexandra Kachaner, Arthur Mageau, Tiphaine Goulenok, Chrystelle François, Nicole Delory, Marie-Paule Chauveheid, Cedric Louenan, Serge Doan, Caroline Halimi, Isabelle Klein, Thomas Papo, Karim Sacré
<p><strong>Background: </strong>Susac syndrome is a rare disease affecting mainly young women and is characterised by an occlusive microvessel disease limited to the brain, retina, and inner ear. No randomised controlled trial has been published or declared as ongoing to investigate treatments for Susac syndrome. We aimed to compare the effect of glucocorticoids given alone or in combination with immunosuppressive agents or intravenous immunoglobulin for the prevention of relapse in patients with Susac syndrome.</p><p><strong>Methods: </strong>The Phenotypic and Etiological Characterization of Susac Syndrome-National Clinical Research Hospital Program study is a prospective national cohort study that started enrolling on Nov 29, 2011, and included all consecutive patients aged 18 years or older with Susac syndrome who were referred to the French reference centre (Department of Internal Medicine, Bichat-Claude Bernard Hospital, Paris). Susac syndrome was defined by either the triad of encephalopathy with typical brain MRI abnormalities, cochleo-vestibular damage, and multiple occlusions of retinal central artery branches, or at least two of the three criteria without any alternative diagnosis. Collected data included fundoscopy, retinal angiography, audiometry, cerebrospinal fluid, brain MRI, and treatment received at diagnosis; months 1, 3, 6, and 12 after diagnosis; and then annually for 5 years or in the case of a relapse. The primary outcome was defined as the first relapse occurring within a 36-month follow-up period from the first day of treatment, characterised by new clinical symptoms or signs, and new abnormalities observed on retinal angiography, audiometry, or brain MRI, necessitating treatment intensification. There was no involvement of people with lived experience at any stage. The study is registered at ClinicalTrials.gov, NCT01481662.</p><p><strong>Findings: </strong>Between Nov 29, 2011, and Dec 2, 2022, 64 patients were included in the study, with a mean age at diagnosis of 35 years (SD 11); 41 (64%) were women and 23 (36%) were men. At diagnosis, 60 patients received glucocorticoids; 40 (63%) of 64 patients received glucocorticoids alone as a first-line therapy while 20 (31%) received glucocorticoids in combination with immunosuppressive agents or intravenous immunoglobulin. Overall, 46 (72%) of 64 patients had a first relapse with a median relapse-free survival time of 3·96 months (95% CI 2·24-16·07). Comparison of relapse-free survival showed no significant difference between the two treatment strategies (hazard ratio [HR] 1·11 [95% CI 0·56-2·17], p=0·76), compared with glucocorticoids alone as the reference group. In patients who first relapsed while treated with glucocorticoids alone, there was no significant difference in second relapse-free survival between those who did or did not receive immunosuppressive agents or intravenous immunoglobulin as a second-line therapy (HR 2·66 [95% CI 0·63-11·18], p=0·18).</p><p><strong>In
{"title":"Immunosuppressive agents or intravenous immunoglobulin in addition to glucocorticoids in the treatment of Susac syndrome: a French national cohort study.","authors":"Alexandra Kachaner, Arthur Mageau, Tiphaine Goulenok, Chrystelle François, Nicole Delory, Marie-Paule Chauveheid, Cedric Louenan, Serge Doan, Caroline Halimi, Isabelle Klein, Thomas Papo, Karim Sacré","doi":"10.1016/S2665-9913(24)00220-0","DOIUrl":"10.1016/S2665-9913(24)00220-0","url":null,"abstract":"<p><strong>Background: </strong>Susac syndrome is a rare disease affecting mainly young women and is characterised by an occlusive microvessel disease limited to the brain, retina, and inner ear. No randomised controlled trial has been published or declared as ongoing to investigate treatments for Susac syndrome. We aimed to compare the effect of glucocorticoids given alone or in combination with immunosuppressive agents or intravenous immunoglobulin for the prevention of relapse in patients with Susac syndrome.</p><p><strong>Methods: </strong>The Phenotypic and Etiological Characterization of Susac Syndrome-National Clinical Research Hospital Program study is a prospective national cohort study that started enrolling on Nov 29, 2011, and included all consecutive patients aged 18 years or older with Susac syndrome who were referred to the French reference centre (Department of Internal Medicine, Bichat-Claude Bernard Hospital, Paris). Susac syndrome was defined by either the triad of encephalopathy with typical brain MRI abnormalities, cochleo-vestibular damage, and multiple occlusions of retinal central artery branches, or at least two of the three criteria without any alternative diagnosis. Collected data included fundoscopy, retinal angiography, audiometry, cerebrospinal fluid, brain MRI, and treatment received at diagnosis; months 1, 3, 6, and 12 after diagnosis; and then annually for 5 years or in the case of a relapse. The primary outcome was defined as the first relapse occurring within a 36-month follow-up period from the first day of treatment, characterised by new clinical symptoms or signs, and new abnormalities observed on retinal angiography, audiometry, or brain MRI, necessitating treatment intensification. There was no involvement of people with lived experience at any stage. The study is registered at ClinicalTrials.gov, NCT01481662.</p><p><strong>Findings: </strong>Between Nov 29, 2011, and Dec 2, 2022, 64 patients were included in the study, with a mean age at diagnosis of 35 years (SD 11); 41 (64%) were women and 23 (36%) were men. At diagnosis, 60 patients received glucocorticoids; 40 (63%) of 64 patients received glucocorticoids alone as a first-line therapy while 20 (31%) received glucocorticoids in combination with immunosuppressive agents or intravenous immunoglobulin. Overall, 46 (72%) of 64 patients had a first relapse with a median relapse-free survival time of 3·96 months (95% CI 2·24-16·07). Comparison of relapse-free survival showed no significant difference between the two treatment strategies (hazard ratio [HR] 1·11 [95% CI 0·56-2·17], p=0·76), compared with glucocorticoids alone as the reference group. In patients who first relapsed while treated with glucocorticoids alone, there was no significant difference in second relapse-free survival between those who did or did not receive immunosuppressive agents or intravenous immunoglobulin as a second-line therapy (HR 2·66 [95% CI 0·63-11·18], p=0·18).</p><p><strong>In","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298934","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)00267-4
Todd A Hardy
{"title":"Susac syndrome: challenges of interpreting treatment data in a rare disease.","authors":"Todd A Hardy","doi":"10.1016/S2665-9913(24)00267-4","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00267-4","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298936","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":null,"pages":null},"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}
Pub Date : 2024-09-17DOI: 10.1016/S2665-9913(24)00196-6
Quirine A Dumoulin, Doortje I Krijbolder, Karen Visser, Leroy R Lard, Annette H M van der Helm-van Mil
<p><strong>Background: </strong>Prevention of rheumatoid arthritis has become a definitive target. However, whether prevention of anti-citrullinated protein antibody (ACPA)-negative rheumatoid arthritis is possible is still unknown. We aimed to assess the efficacy of a 1-year course of methotrexate on the development of rheumatoid arthritis in ACPA-negative people with clinically suspect arthralgia and predicted increased risk of rheumatoid arthritis.</p><p><strong>Methods: </strong>For this follow-up analysis, we used 4-year data from the TREAT EARLIER trial, a randomised, double-blind, placebo-controlled, proof-of-concept trial conducted in the southwest region of the Netherlands from which we analysed data collected between April 16, 2015, and Sept 11, 2023. ACPA-positive and ACPA-negative adults aged 18 years or older with arthralgia and subclinical joint inflammation who were at risk of developing rheumatoid arthritis were eligible for enrolment. For TREAT EARLIER, participants were randomly assigned (1:1) to active treatment or placebo. Active treatment consisted of a single intramuscular glucocorticoid injection (120 mg of methylprednisolone) upon inclusion, then a 1-year course of methotrexate. Placebo consisted of a single placebo injection followed by a 1-year course of placebo tablets. Trial visits occurred every 4 months during the first 2 years, at which clinical and questionnaire data were collected. Total follow-up was 4 years. For this analysis, participants were stratified via a prediction model into low risk, increased risk, and high risk of developing persistent, clinically apparent inflammatory arthritis. The primary outcome was development of rheumatoid arthritis, defined as the presence of clinically apparent inflammatory arthritis and clinical diagnosis of rheumatoid arthritis, and was assessed in all TREAT EARLIER participants. Severity of subclinical joint inflammation, physical functioning, and grip strength in ACPA-negative participants was studied in each risk group over a period of 2 years.</p><p><strong>Findings: </strong>901 people with clinically suspect arthralgia were assessed for eligibility and 236 were enrolled in TREAT EARLIER. All 236 participants were included in the intention-to-treat analysis and 217 (92%) completed 4-year follow-up. 154 (65%) of 236 participants were women and 82 (35%) were men, 182 (77%) were ACPA-negative and 54 (23%) were ACPA-positive. Of the 182 randomly assigned ACPA-negative participants, none were predicted to be at high risk of developing persistent, clinically apparent inflammatory arthritis, 66 (36%) at increased risk, and 116 (64%) at low risk. Of the 54 ACPA-positive participants, 24 (44%) were predicted to be at high risk, 30 (56%) at increased risk, and none at low risk. After 4 years, 52 (22%) of 236 participants had developed the primary outcome of rheumatoid arthritis (25 [21%] of 119 in the treatment group and 27 [23%] of 117 in the placebo group). Of the 66 ACPA-negat
{"title":"Development of rheumatoid arthritis after methotrexate in anticitrullinated protein antibody-negative people with clinically suspect arthralgia at risk of rheumatoid arthritis: 4-year data from the TREAT EARLIER trial.","authors":"Quirine A Dumoulin, Doortje I Krijbolder, Karen Visser, Leroy R Lard, Annette H M van der Helm-van Mil","doi":"10.1016/S2665-9913(24)00196-6","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00196-6","url":null,"abstract":"<p><strong>Background: </strong>Prevention of rheumatoid arthritis has become a definitive target. However, whether prevention of anti-citrullinated protein antibody (ACPA)-negative rheumatoid arthritis is possible is still unknown. We aimed to assess the efficacy of a 1-year course of methotrexate on the development of rheumatoid arthritis in ACPA-negative people with clinically suspect arthralgia and predicted increased risk of rheumatoid arthritis.</p><p><strong>Methods: </strong>For this follow-up analysis, we used 4-year data from the TREAT EARLIER trial, a randomised, double-blind, placebo-controlled, proof-of-concept trial conducted in the southwest region of the Netherlands from which we analysed data collected between April 16, 2015, and Sept 11, 2023. ACPA-positive and ACPA-negative adults aged 18 years or older with arthralgia and subclinical joint inflammation who were at risk of developing rheumatoid arthritis were eligible for enrolment. For TREAT EARLIER, participants were randomly assigned (1:1) to active treatment or placebo. Active treatment consisted of a single intramuscular glucocorticoid injection (120 mg of methylprednisolone) upon inclusion, then a 1-year course of methotrexate. Placebo consisted of a single placebo injection followed by a 1-year course of placebo tablets. Trial visits occurred every 4 months during the first 2 years, at which clinical and questionnaire data were collected. Total follow-up was 4 years. For this analysis, participants were stratified via a prediction model into low risk, increased risk, and high risk of developing persistent, clinically apparent inflammatory arthritis. The primary outcome was development of rheumatoid arthritis, defined as the presence of clinically apparent inflammatory arthritis and clinical diagnosis of rheumatoid arthritis, and was assessed in all TREAT EARLIER participants. Severity of subclinical joint inflammation, physical functioning, and grip strength in ACPA-negative participants was studied in each risk group over a period of 2 years.</p><p><strong>Findings: </strong>901 people with clinically suspect arthralgia were assessed for eligibility and 236 were enrolled in TREAT EARLIER. All 236 participants were included in the intention-to-treat analysis and 217 (92%) completed 4-year follow-up. 154 (65%) of 236 participants were women and 82 (35%) were men, 182 (77%) were ACPA-negative and 54 (23%) were ACPA-positive. Of the 182 randomly assigned ACPA-negative participants, none were predicted to be at high risk of developing persistent, clinically apparent inflammatory arthritis, 66 (36%) at increased risk, and 116 (64%) at low risk. Of the 54 ACPA-positive participants, 24 (44%) were predicted to be at high risk, 30 (56%) at increased risk, and none at low risk. After 4 years, 52 (22%) of 236 participants had developed the primary outcome of rheumatoid arthritis (25 [21%] of 119 in the treatment group and 27 [23%] of 117 in the placebo group). Of the 66 ACPA-negat","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298933","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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