Association of Soluble Immune Checkpoint Molecules PD1 and 4‐1BB With CTLA‐4Ig Treatment Response in Early Rheumatoid Arthritis
Objective To investigate whether soluble immune checkpoint molecules in blood are associated with the treatment response to disease‐modifying antirheumatic drugs in early rheumatoid arthritis (eRA). Methods This study included 328 Swedish treatment‐naïve patients with eRA from the Nordic Rheumatic D...
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| Format: | Article |
| Language: | English |
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Wiley
2025-07-01
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| Series: | ACR Open Rheumatology |
| Online Access: | https://doi.org/10.1002/acr2.70069 |
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| author | Tilia Selldén Kristina Lend Jon Lampa Merete Lund Hetland Mikkel Østergaard Tillmann Uhlig Dan Nordström Kim Hørslev‐Petersen Björn Gudbjörnsson Gerdur Gröndal Inger Gjertsson Ronald vanVollenhoven Cristina Maglio Kerstin Andersson Anna‐Karin Hultgård Ekwall Anna‐Carin Lundell Anna Rudin |
| author_facet | Tilia Selldén Kristina Lend Jon Lampa Merete Lund Hetland Mikkel Østergaard Tillmann Uhlig Dan Nordström Kim Hørslev‐Petersen Björn Gudbjörnsson Gerdur Gröndal Inger Gjertsson Ronald vanVollenhoven Cristina Maglio Kerstin Andersson Anna‐Karin Hultgård Ekwall Anna‐Carin Lundell Anna Rudin |
| author_sort | Tilia Selldén |
| collection | DOAJ |
| description | Objective To investigate whether soluble immune checkpoint molecules in blood are associated with the treatment response to disease‐modifying antirheumatic drugs in early rheumatoid arthritis (eRA). Methods This study included 328 Swedish treatment‐naïve patients with eRA from the Nordic Rheumatic Diseases Strategy Trials and Registries (NORD‐STAR) study. Patients were randomized into four treatment groups: methotrexate (MTX) combined with CTLA‐4Ig (n = 90), anti–tumor necrosis factor (n = 83), anti–interleukin‐6 receptor (n = 76), or prednisolone (n = 79). The primary outcome was remission, defined by Clinical Disease Activity Index (CDAI) ≤2.8, assessed at 24 and 48 weeks. Plasma levels of soluble programmed cell death‐1 (sPD1) and soluble 4‐1BB (s4‐1BB) were measured by enzyme‐linked immunosorbent assay at baseline and at weeks 24 and 48 after treatment initiation. Results High baseline levels of sPD1 and s4‐1BB were both associated with CDAI remission at 24 weeks (odds ratio 1.31, 95% confidence interval [CI] 1.04–1.66 and odds ratio 1.50, 95% CI 1.07–2.11, respectively) in patients treated with CTLA‐4Ig with MTX, but not in any other treatment groups. Furthermore, baseline levels of sPD1 or s4‐1BB together with proportions of PD1+ T follicular helper (TFh) cells predicted treatment response to CTLA‐4Ig with MTX after 48 weeks, achieving 90% and 100% positive predictive value, respectively. Conclusion High plasma levels of sPD1 and s4‐1BB are associated with good response to CTLA‐4Ig with MTX therapy in patients with eRA. A combination of sPD1 or 4‐1BB levels and the proportions of PD1+ TFh cells in blood at baseline has potential for predicting remission after CTLA‐4Ig treatment. |
| format | Article |
| id | doaj-art-081d1c8b2a404182910fe60a4bd9c26b |
| institution | Kabale University |
| issn | 2578-5745 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | ACR Open Rheumatology |
| spelling | doaj-art-081d1c8b2a404182910fe60a4bd9c26b2025-08-20T03:58:41ZengWileyACR Open Rheumatology2578-57452025-07-0177n/an/a10.1002/acr2.70069Association of Soluble Immune Checkpoint Molecules PD1 and 4‐1BB With CTLA‐4Ig Treatment Response in Early Rheumatoid ArthritisTilia Selldén0Kristina Lend1Jon Lampa2Merete Lund Hetland3Mikkel Østergaard4Tillmann Uhlig5Dan Nordström6Kim Hørslev‐Petersen7Björn Gudbjörnsson8Gerdur Gröndal9Inger Gjertsson10Ronald vanVollenhoven11Cristina Maglio12Kerstin Andersson13Anna‐Karin Hultgård Ekwall14Anna‐Carin Lundell15Anna Rudin16Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg Gothenburg SwedenDepartment of Rheumatology and Amsterdam Rheumatology Center, Amsterdam University Medical Centres, Amsterdam, The Netherlands, and Rheumatology Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institute and Karolinska University Hospital Stockholm SwedenRheumatology Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institute and Karolinska University Hospital Stockholm SwedenCenter for Rheumatology and Spine Diseases, Copenhagen Center for Arthritis Research, Rigshospitalet, Glostrup, Denmark, and Department of Clinical Medicine, University of Copenhagen Copenhagen DenmarkCenter for Rheumatology and Spine Diseases, Copenhagen Center for Arthritis Research, Rigshospitalet, Glostrup, Denmark, and Department of Clinical Medicine, University of Copenhagen Copenhagen DenmarkDivision of Rheumatology and Research Diakonhjemmet Hospital Oslo NorwayDepartment of Medicine and Rheumatology Helsinki University and University Hospital Helsinki FinlandDanish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg, Denmark, and Department of Regional Health Research, University of Southern Denmark Odense DenmarkCentre for Rheumatology Research, Landspitali University Hospital and Faculty of Medicine, University of Iceland Reykjavik IcelandCentre for Rheumatology Research, Landspitali University Hospital and Faculty of Medicine, University of Iceland Reykjavik IcelandDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg and Department of Rheumatology Sahlgrenska University Hospital Gothenburg SwedenDepartment of Rheumatology and Amsterdam Rheumatology Center, Amsterdam University Medical Centres, Amsterdam, The Netherlands, and Rheumatology Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institute and Karolinska University Hospital Stockholm SwedenDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg and Department of Rheumatology Sahlgrenska University Hospital Gothenburg SwedenDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg Gothenburg SwedenDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg and Department of Rheumatology Sahlgrenska University Hospital Gothenburg SwedenDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg Gothenburg SwedenDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg and Department of Rheumatology Sahlgrenska University Hospital Gothenburg SwedenObjective To investigate whether soluble immune checkpoint molecules in blood are associated with the treatment response to disease‐modifying antirheumatic drugs in early rheumatoid arthritis (eRA). Methods This study included 328 Swedish treatment‐naïve patients with eRA from the Nordic Rheumatic Diseases Strategy Trials and Registries (NORD‐STAR) study. Patients were randomized into four treatment groups: methotrexate (MTX) combined with CTLA‐4Ig (n = 90), anti–tumor necrosis factor (n = 83), anti–interleukin‐6 receptor (n = 76), or prednisolone (n = 79). The primary outcome was remission, defined by Clinical Disease Activity Index (CDAI) ≤2.8, assessed at 24 and 48 weeks. Plasma levels of soluble programmed cell death‐1 (sPD1) and soluble 4‐1BB (s4‐1BB) were measured by enzyme‐linked immunosorbent assay at baseline and at weeks 24 and 48 after treatment initiation. Results High baseline levels of sPD1 and s4‐1BB were both associated with CDAI remission at 24 weeks (odds ratio 1.31, 95% confidence interval [CI] 1.04–1.66 and odds ratio 1.50, 95% CI 1.07–2.11, respectively) in patients treated with CTLA‐4Ig with MTX, but not in any other treatment groups. Furthermore, baseline levels of sPD1 or s4‐1BB together with proportions of PD1+ T follicular helper (TFh) cells predicted treatment response to CTLA‐4Ig with MTX after 48 weeks, achieving 90% and 100% positive predictive value, respectively. Conclusion High plasma levels of sPD1 and s4‐1BB are associated with good response to CTLA‐4Ig with MTX therapy in patients with eRA. A combination of sPD1 or 4‐1BB levels and the proportions of PD1+ TFh cells in blood at baseline has potential for predicting remission after CTLA‐4Ig treatment.https://doi.org/10.1002/acr2.70069 |
| spellingShingle | Tilia Selldén Kristina Lend Jon Lampa Merete Lund Hetland Mikkel Østergaard Tillmann Uhlig Dan Nordström Kim Hørslev‐Petersen Björn Gudbjörnsson Gerdur Gröndal Inger Gjertsson Ronald vanVollenhoven Cristina Maglio Kerstin Andersson Anna‐Karin Hultgård Ekwall Anna‐Carin Lundell Anna Rudin Association of Soluble Immune Checkpoint Molecules PD1 and 4‐1BB With CTLA‐4Ig Treatment Response in Early Rheumatoid Arthritis ACR Open Rheumatology |
| title | Association of Soluble Immune Checkpoint Molecules PD1 and 4‐1BB With CTLA‐4Ig Treatment Response in Early Rheumatoid Arthritis |
| title_full | Association of Soluble Immune Checkpoint Molecules PD1 and 4‐1BB With CTLA‐4Ig Treatment Response in Early Rheumatoid Arthritis |
| title_fullStr | Association of Soluble Immune Checkpoint Molecules PD1 and 4‐1BB With CTLA‐4Ig Treatment Response in Early Rheumatoid Arthritis |
| title_full_unstemmed | Association of Soluble Immune Checkpoint Molecules PD1 and 4‐1BB With CTLA‐4Ig Treatment Response in Early Rheumatoid Arthritis |
| title_short | Association of Soluble Immune Checkpoint Molecules PD1 and 4‐1BB With CTLA‐4Ig Treatment Response in Early Rheumatoid Arthritis |
| title_sort | association of soluble immune checkpoint molecules pd1 and 4 1bb with ctla 4ig treatment response in early rheumatoid arthritis |
| url | https://doi.org/10.1002/acr2.70069 |
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