Kristina Lend, Jon Lampa, Leonid Padyukov, Merete Lund Hetland, Marte Schrumpf Heiberg, Dan C Nordström, Michael T Nurmohamed, Anna Rudin, Mikkel Østergaard, Espen A Haavardsholm, Kim Hørslev-Petersen, Till Uhlig, Tuulikki Sokka-Isler, Bjorn Gudbjornsson, Gerdur Grondal, Giulia Frazzei, Jeroen Christiaans, Gertjan Wolbink, Theo Rispens, Jos W R Twisk, Ronald F van Vollenhoven
{"title":"类风湿因子、抗瓜氨酸蛋白抗体和共同表位与早期类风湿关节炎患者对初始治疗的临床反应的关系：一项随机对照试验的数据。","authors":"Kristina Lend, Jon Lampa, Leonid Padyukov, Merete Lund Hetland, Marte Schrumpf Heiberg, Dan C Nordström, Michael T Nurmohamed, Anna Rudin, Mikkel Østergaard, Espen A Haavardsholm, Kim Hørslev-Petersen, Till Uhlig, Tuulikki Sokka-Isler, Bjorn Gudbjornsson, Gerdur Grondal, Giulia Frazzei, Jeroen Christiaans, Gertjan Wolbink, Theo Rispens, Jos W R Twisk, Ronald F van Vollenhoven","doi":"10.1136/ard-2024-226024","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT).</p><p><strong>Methods: </strong>Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking.</p><p><strong>Results: </strong>In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks.</p><p><strong>Conclusions: </strong>Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice.</p><p><strong>Trial registration number: </strong>EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":null,"pages":null},"PeriodicalIF":20.3000,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial.\",\"authors\":\"Kristina Lend, Jon Lampa, Leonid Padyukov, Merete Lund Hetland, Marte Schrumpf Heiberg, Dan C Nordström, Michael T Nurmohamed, Anna Rudin, Mikkel Østergaard, Espen A Haavardsholm, Kim Hørslev-Petersen, Till Uhlig, Tuulikki Sokka-Isler, Bjorn Gudbjornsson, Gerdur Grondal, Giulia Frazzei, Jeroen Christiaans, Gertjan Wolbink, Theo Rispens, Jos W R Twisk, Ronald F van Vollenhoven\",\"doi\":\"10.1136/ard-2024-226024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT).</p><p><strong>Methods: </strong>Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking.</p><p><strong>Results: </strong>In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks.</p><p><strong>Conclusions: </strong>Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice.</p><p><strong>Trial registration number: </strong>EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.</p>\",\"PeriodicalId\":8087,\"journal\":{\"name\":\"Annals of the Rheumatic Diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":20.3000,\"publicationDate\":\"2024-07-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of the Rheumatic Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/ard-2024-226024\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of the Rheumatic Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/ard-2024-226024","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial.
Objectives: To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT).
Methods: Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking.
Results: In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks.
Conclusions: Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice.
期刊介绍：
Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal covering all aspects of rheumatology, which includes the full spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research, including the most important recommendations for the management of various conditions.
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