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":" ","pages":""},"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":" ","pages":""},"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":"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}
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":" ","pages":""},"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}
Pub Date : 2024-09-17DOI: 10.1016/S2665-9913(24)00226-1
Serena Bugatti, Georg Schett
{"title":"Prevention of seronegative rheumatoid arthritis: an entity of its own.","authors":"Serena Bugatti, Georg Schett","doi":"10.1016/S2665-9913(24)00226-1","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00226-1","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298935","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 : 2024-09-10DOI: 10.1016/S2665-9913(24)00249-2
Begonya Alcacer-Pitarch , Francesco Del Galdo , Helena Marzo-Ortega
{"title":"Clinical hypnosis and pain management in sharp debridement of skin ulcers in immune-mediated inflammatory diseases","authors":"Begonya Alcacer-Pitarch , Francesco Del Galdo , Helena Marzo-Ortega","doi":"10.1016/S2665-9913(24)00249-2","DOIUrl":"10.1016/S2665-9913(24)00249-2","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 10","pages":"Pages e664-e665"},"PeriodicalIF":15.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142262180","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 : 2024-09-02DOI: 10.1016/S2665-9913(24)00194-2
Zhenyu Zhong MD , Prof Dan Deng PhD , Yu Gao MD , Qingqing Bu MAS , Lingyu Dai MD , Xiaojie Feng MD , Chong Tang MD , Xiang Luo BS , Yao Wang BS , Chunjiang Zhou MPA , Guannan Su PhD , Prof Peizeng Yang MD
<div><h3>Background</h3><div>Data from head-to-head trials of immunomodulatory therapies for Behçet's disease are scarce. We aimed to compare the efficacy and safety of ciclosporin, interferon alfa-2a, and adalimumab, each combined with corticosteroids, in preventing uveitis relapse in patients with severe Behçet's disease.</div></div><div><h3>Methods</h3><div>We did a randomised, open-label, assessor-masked, head-to-head trial at a large, specialised uveitis centre in Chongqing, China. Patients aged 18 years or older with severe Behçet's disease uveitis on corticosteroids and naive to anti-TNF therapy were eligible. Patients were randomly assigned in a 1:1:1 ratio to ciclosporin (2–5 mg/kg per day orally), interferon alfa-2a (3 million IU per day subcutaneously), or adalimumab (40 mg every 2 weeks subcutaneously), each combined with a tapering dose of corticosteroids with subsequent dose adjustments. The primary outcome was the annualised relapse rate of uveitis, assessed in the full analysis set (all randomly assigned patients with at least one post-baseline assessment). The non-inferiority margin of difference between the interferon alfa-2a and adalimumab groups was set to 1·0 for the primary outcome. Safety was assessed in all patients who received at least one dose of trial drugs. Individuals with lived experience of Behçet's disease uveitis were involved in the trial design and implementation. This study is registered with Chinese Clinical Trial Registry, ChiCTR2000031637. The trial is ongoing, but is closed to new participants.</div></div><div><h3>Findings</h3><div>Between May 12, 2020, and Feb 22, 2022, a total of 270 patients (mean age 38·1 years [SD 9·8]; 213 [79%] men, 57 [21%] women; 270 [100%] east Asian ethnicity) were randomly assigned to ciclosporin, interferon alfa-2a, or adalimumab (n=90 in each group); 261 patients were included in the full analysis set. For the primary outcome, the least-squares mean was 1·84 (95% CI 1·40 to 2·44) with ciclosporin, 1·44 (1·10 to 1·89) with interferon alfa-2a, and 0·95 (0·64 to 1·40) with adalimumab. The annualised relapse rate was significantly higher in patients receiving ciclosporin than in those receiving adalimumab (least-squares mean difference 0·90 [95% CI 0·27 to 1·53]; p=0·0054 for superiority). The least-squares mean difference between interferon alfa-2a and adalimumab was 0·50 (–0·04 to 1·04), which did not meet non-inferiority criteria (p=0·034 for non-inferiority). The primary outcome did not differ substantially between interferon alfa-2a and ciclosporin (least-squares mean difference –0·40 [–1·05 to 0·25]; p=0·23 for superiority). Serious adverse events were reported in 12 (13%) of 90 patients on ciclosporin plus corticosteroids, eight (9%) of 90 patients on interferon alfa-2a plus corticosteroids, and seven (8%) of 90 patients on adalimumab plus corticosteroids. There were no treatment-related deaths.</div></div><div><h3>Interpretation</h3><div>Adalimumab plus corticosteroids wa
{"title":"Combinations of immunomodulatory agents for prevention of uveitis relapse in patients with severe Behçet's disease already on corticosteroid therapy: a randomised, open-label, head-to-head trial","authors":"Zhenyu Zhong MD , Prof Dan Deng PhD , Yu Gao MD , Qingqing Bu MAS , Lingyu Dai MD , Xiaojie Feng MD , Chong Tang MD , Xiang Luo BS , Yao Wang BS , Chunjiang Zhou MPA , Guannan Su PhD , Prof Peizeng Yang MD","doi":"10.1016/S2665-9913(24)00194-2","DOIUrl":"10.1016/S2665-9913(24)00194-2","url":null,"abstract":"<div><h3>Background</h3><div>Data from head-to-head trials of immunomodulatory therapies for Behçet's disease are scarce. We aimed to compare the efficacy and safety of ciclosporin, interferon alfa-2a, and adalimumab, each combined with corticosteroids, in preventing uveitis relapse in patients with severe Behçet's disease.</div></div><div><h3>Methods</h3><div>We did a randomised, open-label, assessor-masked, head-to-head trial at a large, specialised uveitis centre in Chongqing, China. Patients aged 18 years or older with severe Behçet's disease uveitis on corticosteroids and naive to anti-TNF therapy were eligible. Patients were randomly assigned in a 1:1:1 ratio to ciclosporin (2–5 mg/kg per day orally), interferon alfa-2a (3 million IU per day subcutaneously), or adalimumab (40 mg every 2 weeks subcutaneously), each combined with a tapering dose of corticosteroids with subsequent dose adjustments. The primary outcome was the annualised relapse rate of uveitis, assessed in the full analysis set (all randomly assigned patients with at least one post-baseline assessment). The non-inferiority margin of difference between the interferon alfa-2a and adalimumab groups was set to 1·0 for the primary outcome. Safety was assessed in all patients who received at least one dose of trial drugs. Individuals with lived experience of Behçet's disease uveitis were involved in the trial design and implementation. This study is registered with Chinese Clinical Trial Registry, ChiCTR2000031637. The trial is ongoing, but is closed to new participants.</div></div><div><h3>Findings</h3><div>Between May 12, 2020, and Feb 22, 2022, a total of 270 patients (mean age 38·1 years [SD 9·8]; 213 [79%] men, 57 [21%] women; 270 [100%] east Asian ethnicity) were randomly assigned to ciclosporin, interferon alfa-2a, or adalimumab (n=90 in each group); 261 patients were included in the full analysis set. For the primary outcome, the least-squares mean was 1·84 (95% CI 1·40 to 2·44) with ciclosporin, 1·44 (1·10 to 1·89) with interferon alfa-2a, and 0·95 (0·64 to 1·40) with adalimumab. The annualised relapse rate was significantly higher in patients receiving ciclosporin than in those receiving adalimumab (least-squares mean difference 0·90 [95% CI 0·27 to 1·53]; p=0·0054 for superiority). The least-squares mean difference between interferon alfa-2a and adalimumab was 0·50 (–0·04 to 1·04), which did not meet non-inferiority criteria (p=0·034 for non-inferiority). The primary outcome did not differ substantially between interferon alfa-2a and ciclosporin (least-squares mean difference –0·40 [–1·05 to 0·25]; p=0·23 for superiority). Serious adverse events were reported in 12 (13%) of 90 patients on ciclosporin plus corticosteroids, eight (9%) of 90 patients on interferon alfa-2a plus corticosteroids, and seven (8%) of 90 patients on adalimumab plus corticosteroids. There were no treatment-related deaths.</div></div><div><h3>Interpretation</h3><div>Adalimumab plus corticosteroids wa","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 11","pages":"Pages e780-e790"},"PeriodicalIF":15.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141389","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 : 2024-09-02DOI: 10.1016/S2665-9913(24)00222-4
Jian-long Guan , Jun Zou
{"title":"Uveitis relapse in Behçet's disease: a more nuanced approach is needed","authors":"Jian-long Guan , Jun Zou","doi":"10.1016/S2665-9913(24)00222-4","DOIUrl":"10.1016/S2665-9913(24)00222-4","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 11","pages":"Pages e739-e740"},"PeriodicalIF":15.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141390","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 : 2024-08-28DOI: 10.1016/S2665-9913(24)00189-9
Gabrielle Virgili-Gervais MSc , Bianca Matthews BSc , Elsa-Lynn Nassar MSc , Marie-Eve Carrier MSc , Linda Kwakkenbos PhD , John D Pauling MD , Prof Susan J Bartlett PhD , Amy Gietzen , Karen Gottesman BA , Geneviève Guillot PDt , Marie Hudson MD , Laura K Hummers MD , Amanda Lawrie-Jones , Prof Vanessa L Malcarne PhD , Prof Maureen D Mayes MD , Michelle Richard DSW , Maureen Sauvé BA , Robyn K Wojeck PhD , Prof Luc Mouthon MD , Andrea Benedetti PhD , Sabrina Provencher
Background
Raynaud's phenomenon is the earliest and most common systemic sclerosis manifestation. Episodes can be triggered by cold exposure and ambient temperature changes. Small studies have found that Raynaud's phenomenon outcomes were associated with season. We aimed to map the degree that differences in ambient temperature are associated with Raynaud's phenomenon outcomes across the temperature spectrum.
Methods
People with Raynaud's phenomenon secondary to systemic sclerosis in the Scleroderma Patient-centered Intervention Network Cohort completed past-week Raynaud's phenomenon severity assessments (0–10 numerical rating scale) at enrolment and longitudinally at 3-month intervals. Mean daily temperature and feels like temperature, which incorporates wind chill and humidity, for the week before each assessment were extracted for each participant from a weather site close to the participant's recruiting centre via the Iowa Environmental Mesonet. We used linear mixed models with basis splines to flexibly model non-linear changes in Raynaud's phenomenon severity across the temperature spectrum. People with lived experience of systemic sclerosis contributed to the study design and interpretation.
Findings
Between April 15, 2014 and Aug 1, 2023, we included data on 20 233 Raynaud's phenomenon severity assessments from 2243 participants. 1964 (88%) of 2243 participants were women, 279 (12%) were men, and 1813 (82%) were White. Mean age was 54·8 (SD 12·7) years. The maximum predicted Raynaud's phenomenon severity score was 6·8 points (95% CI 5·6–8·1), which occurred at –25°C. Severity scores decreased minimally from –15°C to 5°C (0·05–0·21 points per 5°C difference), then decreased in larger steps between 5°C and 25°C (0·37–0·54 points per 5°C difference). The minimum predicted score was at 25°C (2·6 points [95% CI 2·5–2·7]). Scores increased at temperatures above 25°C to 3·5 points (3·0–4·1) at 35°C and 5·6 points (4·5–6·8) at 40°C. Results were similar for feels like temperature.
Interpretation
Raynaud's phenomenon severity is worst at very cold temperatures but also increases with very warm temperatures, presumably due to air conditioning. Clinical management and Raynaud's phenomenon intervention trial designs should consider temperature patterns.
Funding
Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University.
{"title":"The association of outdoor temperature and self-reported Raynaud's phenomenon severity among people with systemic sclerosis: a Scleroderma Patient-centered Intervention Network Cohort study","authors":"Gabrielle Virgili-Gervais MSc , Bianca Matthews BSc , Elsa-Lynn Nassar MSc , Marie-Eve Carrier MSc , Linda Kwakkenbos PhD , John D Pauling MD , Prof Susan J Bartlett PhD , Amy Gietzen , Karen Gottesman BA , Geneviève Guillot PDt , Marie Hudson MD , Laura K Hummers MD , Amanda Lawrie-Jones , Prof Vanessa L Malcarne PhD , Prof Maureen D Mayes MD , Michelle Richard DSW , Maureen Sauvé BA , Robyn K Wojeck PhD , Prof Luc Mouthon MD , Andrea Benedetti PhD , Sabrina Provencher","doi":"10.1016/S2665-9913(24)00189-9","DOIUrl":"10.1016/S2665-9913(24)00189-9","url":null,"abstract":"<div><h3>Background</h3><div>Raynaud's phenomenon is the earliest and most common systemic sclerosis manifestation. Episodes can be triggered by cold exposure and ambient temperature changes. Small studies have found that Raynaud's phenomenon outcomes were associated with season. We aimed to map the degree that differences in ambient temperature are associated with Raynaud's phenomenon outcomes across the temperature spectrum.</div></div><div><h3>Methods</h3><div>People with Raynaud's phenomenon secondary to systemic sclerosis in the Scleroderma Patient-centered Intervention Network Cohort completed past-week Raynaud's phenomenon severity assessments (0–10 numerical rating scale) at enrolment and longitudinally at 3-month intervals. Mean daily temperature and feels like temperature, which incorporates wind chill and humidity, for the week before each assessment were extracted for each participant from a weather site close to the participant's recruiting centre via the Iowa Environmental Mesonet. We used linear mixed models with basis splines to flexibly model non-linear changes in Raynaud's phenomenon severity across the temperature spectrum. People with lived experience of systemic sclerosis contributed to the study design and interpretation.</div></div><div><h3>Findings</h3><div>Between April 15, 2014 and Aug 1, 2023, we included data on 20 233 Raynaud's phenomenon severity assessments from 2243 participants. 1964 (88%) of 2243 participants were women, 279 (12%) were men, and 1813 (82%) were White. Mean age was 54·8 (SD 12·7) years. The maximum predicted Raynaud's phenomenon severity score was 6·8 points (95% CI 5·6–8·1), which occurred at –25°C. Severity scores decreased minimally from –15°C to 5°C (0·05–0·21 points per 5°C difference), then decreased in larger steps between 5°C and 25°C (0·37–0·54 points per 5°C difference). The minimum predicted score was at 25°C (2·6 points [95% CI 2·5–2·7]). Scores increased at temperatures above 25°C to 3·5 points (3·0–4·1) at 35°C and 5·6 points (4·5–6·8) at 40°C. Results were similar for feels like temperature.</div></div><div><h3>Interpretation</h3><div>Raynaud's phenomenon severity is worst at very cold temperatures but also increases with very warm temperatures, presumably due to air conditioning. Clinical management and Raynaud's phenomenon intervention trial designs should consider temperature patterns.</div></div><div><h3>Funding</h3><div>Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University.</div></div>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 10","pages":"Pages e684-e692"},"PeriodicalIF":15.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113579","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 : 2024-08-28DOI: 10.1016/S2665-9913(24)00243-1
Maurizio Cutolo , Vanessa Smith , Elvis Hysa
{"title":"Outdoor temperatures and Raynaud's phenomenon in patients with systemic sclerosis","authors":"Maurizio Cutolo , Vanessa Smith , Elvis Hysa","doi":"10.1016/S2665-9913(24)00243-1","DOIUrl":"10.1016/S2665-9913(24)00243-1","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 10","pages":"Pages e655-e657"},"PeriodicalIF":15.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113578","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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