Pub Date : 2025-02-27DOI: 10.1016/S2665-9913(25)00005-0
Qingping Yao
{"title":"The same genotype gives rise to a spectrum of disorders.","authors":"Qingping Yao","doi":"10.1016/S2665-9913(25)00005-0","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00005-0","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536982","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 : 2025-02-27DOI: 10.1016/S2665-9913(24)00348-5
Jerome Hadjadj, Anna Wolfers, Oleg Borisov, Derek Hazard, Ronan Leahy, Marie Jeanpierre, Alexandre Belot, Shahrzad Bakhtiar, Fabian Hauck, Pui Y Lee, Stephano Volpi, Serena Palmeri, Vincent Barlogis, Nathalie Aladjidi, Georg Ebetsberger-Dachs, Jerome Avouac, Fabienne Charbit-Henrion, Morgane Cheminant, Jean Donadieu, Sujal Ghosh, David P Hoytema van Konijnenburg, Julia Körholz, Jacinta Bustamante, Jeremie Rosain, Lisa Forbes Satter, Ingrid Selmeryd, Georgios Sogkas, Benedicte Neven, Frederic Rieux-Laucat, Stephan Ehl
<p><strong>Background: </strong>Suppressor of cytokine signalling 1 (SOCS1) insufficiency is an inborn error of immunity affecting the negative regulation of cytokine and growth factor signalling. We aimed to enhance the understanding of clinical manifestations, disease trajectories, disease penetrance, and the effect of Janus kinase (JAK) inhibition in individuals with SOCS1 insufficiency.</p><p><strong>Methods: </strong>This study used data from two independent cohorts: the European Society for Immunodeficiencies (ESID) registry and the UK Biobank. Participants from the ESID registry were from nine European countries (Austria, Belgium, France, Germany, Ireland, Italy, Portugal, Sweden, and Ukraine), China, Taiwan, and the USA. Participants from the ESID registry were eligible if they had heterozygous, functionally validated SOCS1 variants; participants from the UK Biobank were included if they had any SOCS1 variant detected in the ESID registry cohort or any other SOCS1 variant that was classed as high-impact. Clinical manifestations of the underlying SOCS1 insufficiency were documented and summarised into nine subgroups, with ICD-10 diagnosis codes collected for participants from the UK Biobank. Participants from the ESID registry were tested for relevant autoantibodies in their local laboratory. Responses to JAK inhibitor treatment in participants from the ESID registry were assessed by the treating physician using a visual analogue scale. Descriptive statistics were used for analysis. People with lived experience were not involved in the study design.</p><p><strong>Findings: </strong>We included 119 participants with SOCS1 insufficiency: 67 from the ESID registry, enrolled between Feb 15, 2021, and Dec 31, 2023, and 52 from the UK Biobank. Of the 67 participants from the ESID registry, 39 (58%) were female, 28 (42%) were male, and the median age was 28 years (IQR 15-44, range 2-85). 27 different monoallelic SOCS1 variants were identified in these participants. 62 (93%) of the 67 participants in the ESID registry cohort were symptomatic and five (7%) were asymptomatic family members; of the 62 participants with symptoms, allergy (33 [50%]), inflammatory gastrointestinal (22 [36%]) and skin (18 [29%]) manifestations, autoimmune cytopenia (24 [39%]), and lymphoproliferation (23 [37%]) were most frequent. Rheumatological manifestations (23 [37%]) included systemic lupus erythematosus, Sjögren's disease, and rheumatoid arthritis, with typical autoantibody profiles. 42 (68%) of the 62 symptomatic participants had at least three different manifestations. In the UK Biobank we found 52 participants carrying high-impact SOCS1 variants; 29 (56%) were female, 23 (44%) were male, and the median age was 72 years (65-78, 57-86). Only 30 (58%) of these participants had developed manifestations that were potentially related to SOCS1 insufficiency. Allergy and rheumatological manifestations were more common in participants from the UK Biobank than the ESID re
{"title":"Clinical manifestations, disease penetrance, and treatment in individuals with SOCS1 insufficiency: a registry-based and population-based study.","authors":"Jerome Hadjadj, Anna Wolfers, Oleg Borisov, Derek Hazard, Ronan Leahy, Marie Jeanpierre, Alexandre Belot, Shahrzad Bakhtiar, Fabian Hauck, Pui Y Lee, Stephano Volpi, Serena Palmeri, Vincent Barlogis, Nathalie Aladjidi, Georg Ebetsberger-Dachs, Jerome Avouac, Fabienne Charbit-Henrion, Morgane Cheminant, Jean Donadieu, Sujal Ghosh, David P Hoytema van Konijnenburg, Julia Körholz, Jacinta Bustamante, Jeremie Rosain, Lisa Forbes Satter, Ingrid Selmeryd, Georgios Sogkas, Benedicte Neven, Frederic Rieux-Laucat, Stephan Ehl","doi":"10.1016/S2665-9913(24)00348-5","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00348-5","url":null,"abstract":"<p><strong>Background: </strong>Suppressor of cytokine signalling 1 (SOCS1) insufficiency is an inborn error of immunity affecting the negative regulation of cytokine and growth factor signalling. We aimed to enhance the understanding of clinical manifestations, disease trajectories, disease penetrance, and the effect of Janus kinase (JAK) inhibition in individuals with SOCS1 insufficiency.</p><p><strong>Methods: </strong>This study used data from two independent cohorts: the European Society for Immunodeficiencies (ESID) registry and the UK Biobank. Participants from the ESID registry were from nine European countries (Austria, Belgium, France, Germany, Ireland, Italy, Portugal, Sweden, and Ukraine), China, Taiwan, and the USA. Participants from the ESID registry were eligible if they had heterozygous, functionally validated SOCS1 variants; participants from the UK Biobank were included if they had any SOCS1 variant detected in the ESID registry cohort or any other SOCS1 variant that was classed as high-impact. Clinical manifestations of the underlying SOCS1 insufficiency were documented and summarised into nine subgroups, with ICD-10 diagnosis codes collected for participants from the UK Biobank. Participants from the ESID registry were tested for relevant autoantibodies in their local laboratory. Responses to JAK inhibitor treatment in participants from the ESID registry were assessed by the treating physician using a visual analogue scale. Descriptive statistics were used for analysis. People with lived experience were not involved in the study design.</p><p><strong>Findings: </strong>We included 119 participants with SOCS1 insufficiency: 67 from the ESID registry, enrolled between Feb 15, 2021, and Dec 31, 2023, and 52 from the UK Biobank. Of the 67 participants from the ESID registry, 39 (58%) were female, 28 (42%) were male, and the median age was 28 years (IQR 15-44, range 2-85). 27 different monoallelic SOCS1 variants were identified in these participants. 62 (93%) of the 67 participants in the ESID registry cohort were symptomatic and five (7%) were asymptomatic family members; of the 62 participants with symptoms, allergy (33 [50%]), inflammatory gastrointestinal (22 [36%]) and skin (18 [29%]) manifestations, autoimmune cytopenia (24 [39%]), and lymphoproliferation (23 [37%]) were most frequent. Rheumatological manifestations (23 [37%]) included systemic lupus erythematosus, Sjögren's disease, and rheumatoid arthritis, with typical autoantibody profiles. 42 (68%) of the 62 symptomatic participants had at least three different manifestations. In the UK Biobank we found 52 participants carrying high-impact SOCS1 variants; 29 (56%) were female, 23 (44%) were male, and the median age was 72 years (65-78, 57-86). Only 30 (58%) of these participants had developed manifestations that were potentially related to SOCS1 insufficiency. Allergy and rheumatological manifestations were more common in participants from the UK Biobank than the ESID re","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536736","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 : 2025-02-24DOI: 10.1016/S2665-9913(25)00037-2
The Lancet Rheumatology Editors
{"title":"Thank you to our contributors and peer reviewers in 2024","authors":"The Lancet Rheumatology Editors","doi":"10.1016/S2665-9913(25)00037-2","DOIUrl":"10.1016/S2665-9913(25)00037-2","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 3","pages":"Pages e154-e155"},"PeriodicalIF":15.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478521","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 : 2025-02-24DOI: 10.1016/S2665-9913(25)00035-9
The Lancet Rheumatology
{"title":"A new era of non-opioid analgesics?","authors":"The Lancet Rheumatology","doi":"10.1016/S2665-9913(25)00035-9","DOIUrl":"10.1016/S2665-9913(25)00035-9","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 3","pages":"Page e145"},"PeriodicalIF":15.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478523","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 : 2025-02-24DOI: 10.1016/S2665-9913(25)00038-4
The Lancet Rheumatology Editors
{"title":"Thank you to The Lancet Rheumatology's peer reviewers in 2024","authors":"The Lancet Rheumatology Editors","doi":"10.1016/S2665-9913(25)00038-4","DOIUrl":"10.1016/S2665-9913(25)00038-4","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 3","pages":"Pages e155-e158"},"PeriodicalIF":15.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478522","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 : 2025-02-18DOI: 10.1016/S2665-9913(24)00312-6
Walter P Maksymowych, Robert G W Lambert, Rebecca J Bolce, Natalia Bello, Baojin Zhu, Jeffrey R Lisse, Mikkel Østergaard
<p><strong>Background: </strong>The effect of biological disease-modifying antirheumatic drugs (DMARDs) on sacroiliac joint lesions over 52 weeks in biological DMARD-naive patients with radiographic axial spondyloarthritis is unknown. This post-hoc analysis evaluated the effect of ixekizumab and adalimumab versus placebo on structural lesions in sacroiliac joints assessed by MRI in patients naive to biological DMARDs with radiographic axial spondyloarthritis from the COAST-V study.</p><p><strong>Methods: </strong>COAST-V was a phase 3, multicentre, randomised, double-blind, placebo-controlled trial with an active reference arm done over 52 weeks at 84 sites in 12 countries. Eligible patients were adults (aged ≥18 years) naive to biological DMARDs with active radiographic axial spondyloarthritis, radiographic evidence of sacroiliitis, and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs. Patients were randomly assigned (1:1:1:1) to 80 mg ixekizumab every 2 weeks (Q2W) or every 4 weeks (Q4W), 40 mg adalimumab Q2W, or placebo. At week 16, patients receiving placebo or adalimumab were randomly assigned (1:1) again to ixekizumab Q2W or ixekizumab Q4W. Post-hoc analyses of patients with MRI available at baseline, 16 weeks, and 52 weeks are reported. MRIs were scored using the Spondyloarthritis Research Consortium of Canada sacroiliac joint structural scores for erosion, backfill, fat lesions, and ankylosis. ANCOVA was used for treatment comparisons in observed cases adjusting for baseline values, bone marrow oedema, and stratification factors. Subgroup analyses by sex, HLA-B27, and baseline bone marrow oedema were done.</p><p><strong>Findings: </strong>Between June 20, 2016, and Aug 22, 2017, 341 patients were enrolled in the COAST-V study. MRI scans were available for 325 (95%) of 341 patients at baseline and week 16, and for 301 (88%) patients at week 52. 264 (81%) of 325 patients were male and 61 (19%) were female, and the mean age was 41·5 years (SD 11·6). At week 16, erosion significantly decreased versus placebo in the ixekizumab Q2W group (least squares mean -0·91 [SE 0·19] vs 0·10 [0·18]; p<0·0001) and the ixekizumab Q4W group (-0·57 [SE 0·19]; p=0·0086]); the effect of adalimumab was similar. Backfill significantly increased from baseline to week 16 in ixekizumab Q2W versus placebo (0·52 [0·12] vs 0·04 [0·12]; p=0·0042). At week 16, decreases in erosion differed significantly between the placebo group and ixekizumab Q2W or Q4W groups, and differences were seen by sex, HLA-B27 status, and baseline bone marrow oedema score. At week 52, at both ixekizumab doses, further changes were observed in erosion and backfill, which were greatest with continuous ixekizumab Q2W (mean erosion -1·50 [SD 2·70], mean backfill 0·76 [SD 2·09]). A decrease in erosion was also noted in patients switching from adalimumab to ixekizumab at week 16. COAST-V was registered with ClinicalTrials.gov (NCT02696785).</p><p><strong>Interpretation:
{"title":"The effect of ixekizumab treatment on MRI sacroiliac joint structural lesions in patients with radiographic axial spondyloarthritis: post-hoc analysis of a 52-week, randomised, placebo-controlled trial with an active reference arm.","authors":"Walter P Maksymowych, Robert G W Lambert, Rebecca J Bolce, Natalia Bello, Baojin Zhu, Jeffrey R Lisse, Mikkel Østergaard","doi":"10.1016/S2665-9913(24)00312-6","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00312-6","url":null,"abstract":"<p><strong>Background: </strong>The effect of biological disease-modifying antirheumatic drugs (DMARDs) on sacroiliac joint lesions over 52 weeks in biological DMARD-naive patients with radiographic axial spondyloarthritis is unknown. This post-hoc analysis evaluated the effect of ixekizumab and adalimumab versus placebo on structural lesions in sacroiliac joints assessed by MRI in patients naive to biological DMARDs with radiographic axial spondyloarthritis from the COAST-V study.</p><p><strong>Methods: </strong>COAST-V was a phase 3, multicentre, randomised, double-blind, placebo-controlled trial with an active reference arm done over 52 weeks at 84 sites in 12 countries. Eligible patients were adults (aged ≥18 years) naive to biological DMARDs with active radiographic axial spondyloarthritis, radiographic evidence of sacroiliitis, and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs. Patients were randomly assigned (1:1:1:1) to 80 mg ixekizumab every 2 weeks (Q2W) or every 4 weeks (Q4W), 40 mg adalimumab Q2W, or placebo. At week 16, patients receiving placebo or adalimumab were randomly assigned (1:1) again to ixekizumab Q2W or ixekizumab Q4W. Post-hoc analyses of patients with MRI available at baseline, 16 weeks, and 52 weeks are reported. MRIs were scored using the Spondyloarthritis Research Consortium of Canada sacroiliac joint structural scores for erosion, backfill, fat lesions, and ankylosis. ANCOVA was used for treatment comparisons in observed cases adjusting for baseline values, bone marrow oedema, and stratification factors. Subgroup analyses by sex, HLA-B27, and baseline bone marrow oedema were done.</p><p><strong>Findings: </strong>Between June 20, 2016, and Aug 22, 2017, 341 patients were enrolled in the COAST-V study. MRI scans were available for 325 (95%) of 341 patients at baseline and week 16, and for 301 (88%) patients at week 52. 264 (81%) of 325 patients were male and 61 (19%) were female, and the mean age was 41·5 years (SD 11·6). At week 16, erosion significantly decreased versus placebo in the ixekizumab Q2W group (least squares mean -0·91 [SE 0·19] vs 0·10 [0·18]; p<0·0001) and the ixekizumab Q4W group (-0·57 [SE 0·19]; p=0·0086]); the effect of adalimumab was similar. Backfill significantly increased from baseline to week 16 in ixekizumab Q2W versus placebo (0·52 [0·12] vs 0·04 [0·12]; p=0·0042). At week 16, decreases in erosion differed significantly between the placebo group and ixekizumab Q2W or Q4W groups, and differences were seen by sex, HLA-B27 status, and baseline bone marrow oedema score. At week 52, at both ixekizumab doses, further changes were observed in erosion and backfill, which were greatest with continuous ixekizumab Q2W (mean erosion -1·50 [SD 2·70], mean backfill 0·76 [SD 2·09]). A decrease in erosion was also noted in patients switching from adalimumab to ixekizumab at week 16. COAST-V was registered with ClinicalTrials.gov (NCT02696785).</p><p><strong>Interpretation: ","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473360","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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