Low Th2 and high PD1+ TFh cells in blood predict remission after CTLA-4Ig treatment for 48 weeks in early rheumatoid arthritis

Tilia Selldén, Kerstin Andersson, Inger Gjertsson, Anna-Karin Hultgård Ekwall, Kristina Lend, Merete Lund Hetland, Mikkel Østergaard, Tillmann Uhlig, Marte Schrumpf Heiberg, Michael T Nurmohamed, Jon Lampa, Tuulikki Sokka Isler, Dan Nordström, Kim Hørslev-Petersen, Bjorn Gudbjornsson, Gerdur Gröndal, Ronald van Vollenhoven, Cristina Maglio, Anna-Carin Lundell and Anna Rudin

PLOS ONE, 2025, vol. 20, issue 8, 1-18

Abstract: Objective: To determine whether baseline CD4+ T helper (Th) cell subset proportions in blood may serve as predictive biomarkers for achieving remission 48 weeks after initiating CTLA-4Ig, anti-tumor necrosis factor (TNF), or anti-interleukin 6 receptor (IL6R) treatment in patients with early rheumatoid arthritis (eRA). Methods: This study included 60 untreated eRA patients from the larger randomized treatment trial NORD-STAR. They were treated with methotrexate (MTX) combined with either CTLA-4Ig (n = 17), anti-TNF (n = 22), or anti-IL6R (n = 21). Disease activity was assessed by clinical disease activity index (CDAI), C-reactive protein, and erythrocyte sedimentation rate. The primary outcome was remission (CDAI ≤ 2.8) at week 48, and the secondary outcomes were time to reach remission or sustained remission during the 48-week follow-up. CD4+ T cell subset proportions were analyzed fresh by flow cytometry at baseline and at 24 and 48 weeks. Results: In CTLA-4Ig + MTX-treated patients, baseline Th2 together with PD1+ T follicular helper (TFh) cell proportions predicted CDAI remission at week 48 (AUC: 0.986, 95% CI 0.94–1.0). Survival analysis revealed that patients with Th2 proportions below 16.8% or PD1+ TFh proportions above 7.6% at baseline were more likely to achieve remission (log-rank p = 0.002 and p = 0.007, respectively), and sustained remission (log-rank p = 0.01 and p = 0.001, respectively), over the 48-week follow-up. CD4+ T cell subset proportions did not predict remission in patients treated with anti-TNF + MTX or anti-IL6R + MTX. Only CTLA-4Ig treatment reduced PD1+ TFh and PD1neg TFh fractions after 48 weeks. Conclusion: Circulating Th2 and PD1+ TFh cell proportions at baseline may serve as predictive biomarkers for achieving CDAI remission after 48 weeks of CTLA-4Ig treatment in eRA.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0330823

DOI: 10.1371/journal.pone.0330823

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