Laura C Coates, Nadia Corp, Danielle A van der Windt, Enrique R Soriano, Arthur Kavanaugh
Throughout 2020, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has been working to update the GRAPPA treatment recommendations for psoriasis and psoriatic arthritis (PsA). The planned methodology for this update was published previously, and herein we provide an update on progress so far, including details of the systematic literature searches undertaken. GRAPPA is committed to regular updates of its treatment recommendations to incorporate the many significant therapeutic advances that have taken place in the PsA literature since the previous recommendation publication in 2015. The development and updating of treatment recommendations for optimal treatment approaches for patients with PsA has been an important mission of the GRAPPA since its inception. GRAPPA is currently finalizing domain-specific recommendations with an aim to produce updated treatment recommendations for publication in 2021.
{"title":"GRAPPA Treatment Recommendations: An Update From the 2020 GRAPPA Annual Meeting.","authors":"Laura C Coates, Nadia Corp, Danielle A van der Windt, Enrique R Soriano, Arthur Kavanaugh","doi":"10.3899/jrheum.201681","DOIUrl":"https://doi.org/10.3899/jrheum.201681","url":null,"abstract":"<p><p>Throughout 2020, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has been working to update the GRAPPA treatment recommendations for psoriasis and psoriatic arthritis (PsA). The planned methodology for this update was published previously, and herein we provide an update on progress so far, including details of the systematic literature searches undertaken. GRAPPA is committed to regular updates of its treatment recommendations to incorporate the many significant therapeutic advances that have taken place in the PsA literature since the previous recommendation publication in 2015. The development and updating of treatment recommendations for optimal treatment approaches for patients with PsA has been an important mission of the GRAPPA since its inception. GRAPPA is currently finalizing domain-specific recommendations with an aim to produce updated treatment recommendations for publication in 2021.</p>","PeriodicalId":35278,"journal":{"name":"The Journal of rheumatology. Supplement","volume":"97 ","pages":"65-66"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39050097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
William Tillett, Oliver FitzGerald, Laura C Coates, Jon Packham, Deepak R Jadon, Marco Massarotti, Mel Brook, Suzanne Lane, Paul Creamer, Anna Antony, Eleanor Korendowych, Adwaye Rambojun, Neil J McHugh, Philip S Helliwell
Objective To test shortened versions of the psoriatic arthritis (PsA) composite measures for use in routine clinical practice. Methods Clinical and patient-reported outcome measures (PROMs) were assessed in patients with PsA at 3 consecutive follow-up visits in a UK multicenter observational study. Shortened versions of the Composite Psoriatic Arthritis Disease Activity Index (CPDAI) and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Composite Exercise (GRACE) measures were developed using PROMs and tested against the Disease Activity Score in 28 joints (DAS28), composite Disease Activity in Psoriatic Arthritis, and Routine Assessment of Patient Index Data (RAPID3). Discrimination between disease states and responsiveness were tested with the t-score, standardized response mean (SRM), and effect size (ES). Data were presented to members at the GRAPPA 2020 annual meeting and members voted on the recommended composite routine practice. Results The SRM for the GRACE, 3 visual analog scale (VAS), and 4VAS were 0.67, 0.77, and 0.63, respectively, and for CPDAI and shortened CPDAI (sCPDAI) were 0.54 and 0.55, respectively. Shortened versions of the GRACE increased the t-score from 7.8 to 8.7 (3VAS) and 9.0 (4VAS), but reduced the t-score in the CPDAI/sCPDAI from 6.8 and 6.1. The 3VAS and 4VAS had superior performance characteristics to the sCPDAI, DAS28, Disease Activity in Psoriatic Arthritis, and RAPID3 in all tests. Of the members, 60% agreed that the VAS scales contained enough information to assess disease and response to treatment, 53% recommended the 4VAS for use in routine care, and 26% the 3VAS, while leaving 21% undecided. Conclusion. Shortening the GRACE to VAS scores alone enhances the ability to detect status and responsiveness and has the best performance characteristics of the tested composite measures. GRAPPA members recommend further testing of the 3VAS and 4VAS in observational and trial datasets.
{"title":"Composite Measures for Routine Clinical Practice in Psoriatic Arthritis: Testing of Shortened Versions in a UK Multicenter Study.","authors":"William Tillett, Oliver FitzGerald, Laura C Coates, Jon Packham, Deepak R Jadon, Marco Massarotti, Mel Brook, Suzanne Lane, Paul Creamer, Anna Antony, Eleanor Korendowych, Adwaye Rambojun, Neil J McHugh, Philip S Helliwell","doi":"10.3899/jrheum.201675","DOIUrl":"https://doi.org/10.3899/jrheum.201675","url":null,"abstract":"Objective To test shortened versions of the psoriatic arthritis (PsA) composite measures for use in routine clinical practice. Methods Clinical and patient-reported outcome measures (PROMs) were assessed in patients with PsA at 3 consecutive follow-up visits in a UK multicenter observational study. Shortened versions of the Composite Psoriatic Arthritis Disease Activity Index (CPDAI) and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Composite Exercise (GRACE) measures were developed using PROMs and tested against the Disease Activity Score in 28 joints (DAS28), composite Disease Activity in Psoriatic Arthritis, and Routine Assessment of Patient Index Data (RAPID3). Discrimination between disease states and responsiveness were tested with the t-score, standardized response mean (SRM), and effect size (ES). Data were presented to members at the GRAPPA 2020 annual meeting and members voted on the recommended composite routine practice. Results The SRM for the GRACE, 3 visual analog scale (VAS), and 4VAS were 0.67, 0.77, and 0.63, respectively, and for CPDAI and shortened CPDAI (sCPDAI) were 0.54 and 0.55, respectively. Shortened versions of the GRACE increased the t-score from 7.8 to 8.7 (3VAS) and 9.0 (4VAS), but reduced the t-score in the CPDAI/sCPDAI from 6.8 and 6.1. The 3VAS and 4VAS had superior performance characteristics to the sCPDAI, DAS28, Disease Activity in Psoriatic Arthritis, and RAPID3 in all tests. Of the members, 60% agreed that the VAS scales contained enough information to assess disease and response to treatment, 53% recommended the 4VAS for use in routine care, and 26% the 3VAS, while leaving 21% undecided. Conclusion. Shortening the GRACE to VAS scores alone enhances the ability to detect status and responsiveness and has the best performance characteristics of the tested composite measures. GRAPPA members recommend further testing of the 3VAS and 4VAS in observational and trial datasets.","PeriodicalId":35278,"journal":{"name":"The Journal of rheumatology. Supplement","volume":"97 ","pages":"45-49"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39050091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dafna D Gladman, Philip S Helliwell, Denis Poddubnyy, Philip J Mease
This article summarizes sessions that dealt with axial psoriatic arthritis (axPsA) at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2020 virtual meeting. The summary includes the symposium, which comprised a plenary presentation by Dr. Dafna Gladman from Toronto, Canada, as well as a panel discussion with Dr. Philip Helliwell, Dr. Denis Poddubnyy, and Dr. Gladman, moderated by Dr. Philip Mease. In addition, the paper also summarizes Dr. Mease's "Meet the Expert" session, which focused on axPsA.
本文总结了2020年银屑病和银屑病关节炎研究和评估小组(GRAPPA)虚拟会议上处理轴性银屑病关节炎(axPsA)的会议。摘要包括研讨会，其中包括来自加拿大多伦多的Dafna Gladman博士的全体报告，以及由Philip Mease博士主持的与Philip Helliwell博士、Denis Poddubnyy博士和Gladman博士的小组讨论。此外，本文还总结了Mease博士的“Meet the Expert”会议，重点讨论了axPsA。
{"title":"Updates on Axial Psoriatic Arthritis From the 2020 GRAPPA Annual Meeting.","authors":"Dafna D Gladman, Philip S Helliwell, Denis Poddubnyy, Philip J Mease","doi":"10.3899/jrheum.201672","DOIUrl":"https://doi.org/10.3899/jrheum.201672","url":null,"abstract":"<p><p>This article summarizes sessions that dealt with axial psoriatic arthritis (axPsA) at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2020 virtual meeting. The summary includes the symposium, which comprised a plenary presentation by Dr. Dafna Gladman from Toronto, Canada, as well as a panel discussion with Dr. Philip Helliwell, Dr. Denis Poddubnyy, and Dr. Gladman, moderated by Dr. Philip Mease. In addition, the paper also summarizes Dr. Mease's \"Meet the Expert\" session, which focused on axPsA.</p>","PeriodicalId":35278,"journal":{"name":"The Journal of rheumatology. Supplement","volume":"97 ","pages":"30-33"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38983290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristina Callis Duffin, Hervé Bachelez, Philip J Mease, Cheryl Rosen, Amit Garg, Eric Zudak, Ori Elkayam, Joseph F Merola, Jeffrey Chau, Mitsumasa Kishimoto, Victoria Furer, Philip S Helliwell
Pustular psoriasis (PsO) is an uncommon variant of PsO that may present in a generalized or localized fashion with or without musculoskeletal or systemic inflammatory involvement.Generalized pustular PsO (GPP) presents as a widespread acute or subacute pustular eruption that may be familial and is often associated with severe flares and systemic inflammation. The palmoplantar pustulosis variant is localized to palms and soles, whereas acrodermatitis continua of Hallopeau is localized to the nail apparatus. Patients with pustular PsO may have overlapping plaque PsO and may develop psoriatic arthritis (PsA). Pustulosis is also a feature of both synovitis, acne, pustulosis, hyperostosis, osteomyelitis (SAPHO) syndrome and chronic non-bacterial osteomyelitis. At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, members were given an overview of the cutaneous features of pustular PsO, SAPHO, and recent insights into the genetics of GPP, leading to new targeted drug therapies and the development of validated endpoints.
{"title":"Pustular Psoriasis and Associated Musculoskeletal Disorders.","authors":"Kristina Callis Duffin, Hervé Bachelez, Philip J Mease, Cheryl Rosen, Amit Garg, Eric Zudak, Ori Elkayam, Joseph F Merola, Jeffrey Chau, Mitsumasa Kishimoto, Victoria Furer, Philip S Helliwell","doi":"10.3899/jrheum.201673","DOIUrl":"https://doi.org/10.3899/jrheum.201673","url":null,"abstract":"<p><p>Pustular psoriasis (PsO) is an uncommon variant of PsO that may present in a generalized or localized fashion with or without musculoskeletal or systemic inflammatory involvement.Generalized pustular PsO (GPP) presents as a widespread acute or subacute pustular eruption that may be familial and is often associated with severe flares and systemic inflammation. The palmoplantar pustulosis variant is localized to palms and soles, whereas acrodermatitis continua of Hallopeau is localized to the nail apparatus. Patients with pustular PsO may have overlapping plaque PsO and may develop psoriatic arthritis (PsA). Pustulosis is also a feature of both synovitis, acne, pustulosis, hyperostosis, osteomyelitis (SAPHO) syndrome and chronic non-bacterial osteomyelitis. At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, members were given an overview of the cutaneous features of pustular PsO, SAPHO, and recent insights into the genetics of GPP, leading to new targeted drug therapies and the development of validated endpoints.</p>","PeriodicalId":35278,"journal":{"name":"The Journal of rheumatology. Supplement","volume":"97 ","pages":"34-38"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38983291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arthur Kavanaugh, Alla Ishchenko, Rik J Lories, Kurt de Vlam, Zhenrui Shi, Siba P Raychaudhuri, Sam T Hwang
A summary of the research conducted by the recipients of the 2019 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Research Awards is presented. Dr. Alla Ishchenko's project was "Role of Metabolomics in Diagnosis, Disease Severity, and Progression in Psoriasis and Psoriatic Arthritis: A 2-year Prospective Pilot Study" and Dr. Zhenrui Shi's project was "Preclinical Analysis of CCR6 and CCL20 in Mouse and Human Joints, Respectively, as Targets of Therapeutic Intervention in Psoriatic Arthritis."
{"title":"GRAPPA 2019 Research Recipient Awards Report.","authors":"Arthur Kavanaugh, Alla Ishchenko, Rik J Lories, Kurt de Vlam, Zhenrui Shi, Siba P Raychaudhuri, Sam T Hwang","doi":"10.3899/jrheum.201682","DOIUrl":"https://doi.org/10.3899/jrheum.201682","url":null,"abstract":"<p><p>A summary of the research conducted by the recipients of the 2019 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Research Awards is presented. Dr. Alla Ishchenko's project was \"Role of Metabolomics in Diagnosis, Disease Severity, and Progression in Psoriasis and Psoriatic Arthritis: A 2-year Prospective Pilot Study\" and Dr. Zhenrui Shi's project was \"Preclinical Analysis of CCR6 and CCL20 in Mouse and Human Joints, Respectively, as Targets of Therapeutic Intervention in Psoriatic Arthritis.\"</p>","PeriodicalId":35278,"journal":{"name":"The Journal of rheumatology. Supplement","volume":"97 ","pages":"67-68"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39050098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
William Tillett, Oliver FitzGerald, Laura C Coates, Jon Packham, Deepak R Jadon, Marco Massarotti, Mel Brook, Suzanne Lane, Paul Creamer, Anna Antony, Eleanor Korendowych, Adwaye Rambojun, Neil J McHugh, Philip S Helliwell
Objective: To test the addition of pain and fatigue to the Composite Psoriatic Arthritis Disease Activity (CPDAI) and the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) Composite Exercise (GRACE) composite measures of psoriatic arthritis (PsA).
Methods: Clinical and patient-reported outcome measures were assessed in patients with PsA at 3 consecutive follow-up visits over 6 months in a UK multicenter observational study. A pain visual analog scale and Functional Assessment of Chronic Illness Therapy Fatigue scale were added as modifications to the CPDAI and GRACE composite measures. Original and modified versions were tested against the PsA Disease Activity Score (PASDAS) and the Disease Activity Index for PsA (DAPSA). Discrimination between disease states and responsiveness were tested with t-scores, standardized response means (SRMs), and effect sizes. Data were presented to members at the 2020 annual meeting who then voted on the GRAPPA-recommended composite and treatment targets for clinical trials.
Results: One hundred forty-one patients were recruited with a mean PsA disease duration of 6.1 years (range 0-41 yrs). The SRMs for the GRACE and modified GRACE (mGRACE) were 0.67 and 0.64, respectively, and 0.54 and 0.46, respectively, for the CPDAI and modified CPDAI (mCPDAI). The t-scores for the GRACE and mGRACE were unchanged at 7.8 for both, and 6.8 and 7.0 for the CPDAI and mCPDAI, respectively. The PASDAS demonstrated the best responsiveness (SRM 0.84) and discrimination (t-scores 8.3). Most members (82%) agreed the composites should not be modified and 77% voted for the PASDAS as the GRAPPA-recommended composite for clinical trials, with 90% minimal disease activity (MDA) as the target.
Conclusion: Modifying the CPDAI and GRACE with the addition of pain and fatigue does not enhance responsiveness nor the measures' ability to detect disease status in terms of requiring treatment escalation. GRAPPA members voted for the PASDAS as the composite measure in clinical trials and MDA as the target.
{"title":"Composite Measures for Clinical Trials in Psoriatic Arthritis: Testing Pain and Fatigue Modifications in a UK Multicenter Study.","authors":"William Tillett, Oliver FitzGerald, Laura C Coates, Jon Packham, Deepak R Jadon, Marco Massarotti, Mel Brook, Suzanne Lane, Paul Creamer, Anna Antony, Eleanor Korendowych, Adwaye Rambojun, Neil J McHugh, Philip S Helliwell","doi":"10.3899/jrheum.201674","DOIUrl":"https://doi.org/10.3899/jrheum.201674","url":null,"abstract":"<p><strong>Objective: </strong>To test the addition of pain and fatigue to the Composite Psoriatic Arthritis Disease Activity (CPDAI) and the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) Composite Exercise (GRACE) composite measures of psoriatic arthritis (PsA).</p><p><strong>Methods: </strong>Clinical and patient-reported outcome measures were assessed in patients with PsA at 3 consecutive follow-up visits over 6 months in a UK multicenter observational study. A pain visual analog scale and Functional Assessment of Chronic Illness Therapy Fatigue scale were added as modifications to the CPDAI and GRACE composite measures. Original and modified versions were tested against the PsA Disease Activity Score (PASDAS) and the Disease Activity Index for PsA (DAPSA). Discrimination between disease states and responsiveness were tested with <i>t</i>-scores, standardized response means (SRMs), and effect sizes. Data were presented to members at the 2020 annual meeting who then voted on the GRAPPA-recommended composite and treatment targets for clinical trials.</p><p><strong>Results: </strong>One hundred forty-one patients were recruited with a mean PsA disease duration of 6.1 years (range 0-41 yrs). The SRMs for the GRACE and modified GRACE (mGRACE) were 0.67 and 0.64, respectively, and 0.54 and 0.46, respectively, for the CPDAI and modified CPDAI (mCPDAI). The <i>t</i>-scores for the GRACE and mGRACE were unchanged at 7.8 for both, and 6.8 and 7.0 for the CPDAI and mCPDAI, respectively. The PASDAS demonstrated the best responsiveness (SRM 0.84) and discrimination (<i>t</i>-scores 8.3). Most members (82%) agreed the composites should not be modified and 77% voted for the PASDAS as the GRAPPA-recommended composite for clinical trials, with 90% minimal disease activity (MDA) as the target.</p><p><strong>Conclusion: </strong>Modifying the CPDAI and GRACE with the addition of pain and fatigue does not enhance responsiveness nor the measures' ability to detect disease status in terms of requiring treatment escalation. GRAPPA members voted for the PASDAS as the composite measure in clinical trials and MDA as the target.</p>","PeriodicalId":35278,"journal":{"name":"The Journal of rheumatology. Supplement","volume":"97 ","pages":"39-44"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38983292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. Anaparti, P. Agarwal, I. Smolik, N. Mookherjee, H. El-Gabalawy
Objective. Polymorphisms in human major histocompatibility complex (MHC) are the strongest genetic associations with rheumatoid arthritis (RA). Epigenome-wide methylation studies suggest DNA methylation changes within MHC may contribute to disease susceptibility. We profiled MHC-specific methylated CpG (5′–C–phosphate–G–3′) in autoantibody-positive patients with RA and matched unaffected anticitrullinated protein antibodies–negative first-degree relatives (ACPA−/FDR) from an indigenous North American (INA) population that is known to have prevalent RA. Methods. DNA was isolated from whole blood and targeted bisulfite sequencing was used to profile methylated CpG in patients with RA and ACPA−/FDR. Differentially methylated CpG loci (DML) were mapped and gene annotated. Ingenuity pathway analysis (IPA) was used for curating biomolecular networks of mapped genes. Transcript abundance was determined by quantitative (q)PCR. Results. We identified 74 uniquely methylated CpG sites within the MHC region that were differentially methylated in patients with RA (p < 0.05), compared to ACPA−/FDR. Of these, 32 DML were located on 22 genes. IPA showed these genes are involved in regulating the nuclear factor–κB complex and processes involved in antigen presentation, and immune cell crosstalk in autoimmunity. Pearson correlation analysis demonstrated a negative association between differentially methylated CpG in the C6ORF10 gene and risk factors associated with RA. Analysis by qPCR confirmed differential abundance of C6ORF10, TNXB, and HCG18 mRNA in patients with RA compared to ACPA−/FDR. Conclusion. Our results confirm the presence of differential methylation at specific gene loci within the MHC region of INA patients with RA. These epigenetic signatures may precede disease onset, or alternatively, may be a result of developing RA.
{"title":"Whole Blood Targeted Bisulfite Sequencing and Differential Methylation in the C6ORF10 Gene of Patients with Rheumatoid Arthritis","authors":"V. Anaparti, P. Agarwal, I. Smolik, N. Mookherjee, H. El-Gabalawy","doi":"10.3899/jrheum.190376","DOIUrl":"https://doi.org/10.3899/jrheum.190376","url":null,"abstract":"Objective. Polymorphisms in human major histocompatibility complex (MHC) are the strongest genetic associations with rheumatoid arthritis (RA). Epigenome-wide methylation studies suggest DNA methylation changes within MHC may contribute to disease susceptibility. We profiled MHC-specific methylated CpG (5′–C–phosphate–G–3′) in autoantibody-positive patients with RA and matched unaffected anticitrullinated protein antibodies–negative first-degree relatives (ACPA−/FDR) from an indigenous North American (INA) population that is known to have prevalent RA. Methods. DNA was isolated from whole blood and targeted bisulfite sequencing was used to profile methylated CpG in patients with RA and ACPA−/FDR. Differentially methylated CpG loci (DML) were mapped and gene annotated. Ingenuity pathway analysis (IPA) was used for curating biomolecular networks of mapped genes. Transcript abundance was determined by quantitative (q)PCR. Results. We identified 74 uniquely methylated CpG sites within the MHC region that were differentially methylated in patients with RA (p < 0.05), compared to ACPA−/FDR. Of these, 32 DML were located on 22 genes. IPA showed these genes are involved in regulating the nuclear factor–κB complex and processes involved in antigen presentation, and immune cell crosstalk in autoimmunity. Pearson correlation analysis demonstrated a negative association between differentially methylated CpG in the C6ORF10 gene and risk factors associated with RA. Analysis by qPCR confirmed differential abundance of C6ORF10, TNXB, and HCG18 mRNA in patients with RA compared to ACPA−/FDR. Conclusion. Our results confirm the presence of differential methylation at specific gene loci within the MHC region of INA patients with RA. These epigenetic signatures may precede disease onset, or alternatively, may be a result of developing RA.","PeriodicalId":35278,"journal":{"name":"The Journal of rheumatology. Supplement","volume":"8 1","pages":"1614 - 1623"},"PeriodicalIF":0.0,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88383699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junyu Liang, Danyi Xu, Chuanyin Sun, Weiqian Chen, H. Cao, Jin Lin
OBJECTIVE To clarify the prevalence, risk factors, outcome and outcome-related factors of hemophagocytic lymphohistiocytosis (HLH) in patients with dermatomyositis (DM), polymyositis (PM) or clinically amyopathic dermatomyositis (CADM). METHODS Data of patients with DM, PM or CADM who were admitted to the First Affiliated Hospital of Zhejiang University (FAHZJU) from February 2011 to February 2019 were retrospectively collected. Patients diagnosed with HLH constituted the case group. A 1:4 casecontrol study was performed to identify risk factors for HLH in patients with DM, PM or CADM through comparison, univariate and multivariate logistic regression analysis. Intragroup comparison was made within HLH patients to identify factors influencing unfavorable short-term outcome. RESULTS HLH was a rare (4.2%) but fatal (77.8%) complication in patients with DM, PM or CADM. The retrospective case-control study revealed that higher on-admission disease activity (P=0.008), acute exacerbation of interstitial lung disease (AE-ILD, P=0.002) and infection (P=0.002) were risk factors for complication of HLH in patients with DM, PM or CADM. The following intragroup comparison showed that higher on-admission disease activity (P=0.035) and diagnosis of CADM (P=0.039) might influence the short-term outcome of HLH patients. However, no risk factor was identified after false discovery rate correction. CONCLUSION In this study, secondary HLH was a fatal complication with higher on-admission disease activity, AE-ILD and infection working as risk factors. The underlying role of infection and autoimmune abnormality in HLH in connective tissue disease (CTD) was subsequently brought up. Clinical factors influencing the short-term outcome of patients with secondary HLH required further exploration.
{"title":"Hemophagocytic Lymphohistiocytosis: Prevalence, Risk Factors, Outcome, and Outcome-related Factors in Adult Idiopathic Inflammatory Myopathies","authors":"Junyu Liang, Danyi Xu, Chuanyin Sun, Weiqian Chen, H. Cao, Jin Lin","doi":"10.3899/JRHEUM.190542","DOIUrl":"https://doi.org/10.3899/JRHEUM.190542","url":null,"abstract":"OBJECTIVE To clarify the prevalence, risk factors, outcome and outcome-related factors of hemophagocytic lymphohistiocytosis (HLH) in patients with dermatomyositis (DM), polymyositis (PM) or clinically amyopathic dermatomyositis (CADM). METHODS Data of patients with DM, PM or CADM who were admitted to the First Affiliated Hospital of Zhejiang University (FAHZJU) from February 2011 to February 2019 were retrospectively collected. Patients diagnosed with HLH constituted the case group. A 1:4 casecontrol study was performed to identify risk factors for HLH in patients with DM, PM or CADM through comparison, univariate and multivariate logistic regression analysis. Intragroup comparison was made within HLH patients to identify factors influencing unfavorable short-term outcome. RESULTS HLH was a rare (4.2%) but fatal (77.8%) complication in patients with DM, PM or CADM. The retrospective case-control study revealed that higher on-admission disease activity (P=0.008), acute exacerbation of interstitial lung disease (AE-ILD, P=0.002) and infection (P=0.002) were risk factors for complication of HLH in patients with DM, PM or CADM. The following intragroup comparison showed that higher on-admission disease activity (P=0.035) and diagnosis of CADM (P=0.039) might influence the short-term outcome of HLH patients. However, no risk factor was identified after false discovery rate correction. CONCLUSION In this study, secondary HLH was a fatal complication with higher on-admission disease activity, AE-ILD and infection working as risk factors. The underlying role of infection and autoimmune abnormality in HLH in connective tissue disease (CTD) was subsequently brought up. Clinical factors influencing the short-term outcome of patients with secondary HLH required further exploration.","PeriodicalId":35278,"journal":{"name":"The Journal of rheumatology. Supplement","volume":"38 1","pages":"1532 - 1540"},"PeriodicalIF":0.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75684511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-24DOI: 10.21203/rs.3.rs-79368/v1
Fredrik D. Johansson, J. Collins, V. Yau, H. Guan, Seoyoung C. Kim, E. Losina, D. Sontag, Jacklyn Stratton, H. Trinh, J. Greenberg, D. Solomon
Objective Tocilizumab (TCZ) has shown similar efficacy when used as monotherapy as in combination with other treatments for rheumatoid arthritis (RA) in randomized controlled trials (RCTs). We derived a remission prediction score for TCZ monotherapy (TCZm) using RCT data and performed an external validation of the prediction score using real-world data (RWD). Methods We identified patients in the Corrona RA registry who used TCZm (n = 452), and matched the design and patients from 4 RCTs used in previous work (n = 853). Patients were followed to determine remission status at 24 weeks. We compared the performance of remission prediction models in RWD, first based on variables determined in our prior work in RCTs, and then using an extended variable set, comparing logistic regression and random forest models. We included patients on other biologic disease-modifying antirheumatic drug monotherapies (bDMARDm) to improve prediction. Results The fraction of patients observed reaching remission on TCZm by their follow-up visit was 12% (n = 53) in RWD vs 15% (n = 127) in RCTs. Discrimination was good in RWD for the risk score developed in RCTs, with area under the receiver-operating characteristic curve (AUROC) of 0.69 (95% CI 0.62–0.75). Fitting the same logistic regression model to all bDMARDm patients in the RWD improved the AUROC on held-out TCZm patients to 0.72 (95% CI 0.63–0.81). Extending the variable set and adding regularization further increased it to 0.76 (95% CI 0.67–0.84). Conclusion The remission prediction scores, derived in RCTs, discriminated patients in RWD about as well as in RCTs. Discrimination was further improved by retraining models on RWD.
在随机对照试验(RCTs)中，Tocilizumab (TCZ)作为单一疗法与联合其他治疗类风湿性关节炎(RA)的疗效相似。我们使用RCT数据推导出TCZ单药治疗(TCZm)的缓解预测评分，并使用真实世界数据(RWD)对预测评分进行外部验证。方法:我们在Corrona RA注册中心中选择使用TCZm的患者(n = 452)，并将设计与先前工作中使用的4个随机对照试验的患者(n = 853)相匹配。随访患者24周以确定缓解状态。我们比较了RWD缓解预测模型的性能，首先基于我们之前在随机对照试验中确定的变量，然后使用扩展变量集，比较了逻辑回归和随机森林模型。我们纳入了其他生物疾病缓解抗风湿药物单药治疗(bDMARDm)的患者，以提高预测。结果随访时观察到TCZm缓解的患者比例在RWD中为12% (n = 53)，而在rct中为15% (n = 127)。rct的风险评分在RWD中有很好的区分性，受试者-工作特征曲线下面积(AUROC)为0.69 (95% CI 0.62-0.75)。将相同的logistic回归模型拟合到RWD中所有bDMARDm患者，将持牌TCZm患者的AUROC提高到0.72 (95% CI 0.63-0.81)。扩展变量集并加入正则化进一步将其提高到0.76 (95% CI 0.67-0.84)。结论rct的缓解预测评分可以区分RWD患者和rct患者。基于RWD的再培训模型进一步改善了歧视。
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J. O’Neill, Walter Maksymowych. Victoria, British Columbia: Tellwell Talent, 2020, 162 pages, US$68 I was asked to review the Imaging Atlas of Axial Spondyloarthritis by The Journal and my first thought was that I would (as always) say yes, but for such a work, a long review time would be necessary. Still, because the topic of imaging has been of high interest for …
j·奥尼尔，沃尔特·马克西莫维奇。维多利亚，不列颠哥伦比亚省:Tellwell Talent, 2020, 162页，68美元《the Journal》邀请我对《轴性脊柱炎成像图集》(Imaging Atlas of Axial Spondyloarthritis)进行评论，我的第一个想法是(一如既往地)同意，但对于这样的作品，评论时间很长是必要的。尽管如此，因为成像的话题一直是…
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