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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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
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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| Summary: | 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. |
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| ISSN: | 2578-5745 |