Pos0418 Quantitative [11c]-Dpa713 Pet/Ct Imaging Targeting Macrophages for Early Therapeutic Evaluation of Anti-TNF Treatment in Rheumatoid Arthritis Patients

Background: Positive treatment response to anti-tumor necrosis factor (aTNF) therapy in rheumatoid arthritis patients (RA) reaches up to 50-70% [1-4]. Clinical response evaluation can require 3-6 months of treatment to establish efficacy. The remaining non-responding patients potentially face treatment delay and exposure to side-effects. Prior research indicates the potential value of positron emission tomography/computed tomography PET/CT and macrophage tracers to assess disease activity and treatment response in RA patients in early phases of treatment[5, 6]. In this study we investigated a second generation translocator protein PET tracer, [11C]-DPA713, with promising imaging characteristics for visualization of RA activity, aimed at early assessment of aTNF treatment efficacy. Objectives: To determine the association between quantitative whole-body [¹¹C]-DPA713 PET/CT imaging at baseline and at 4 weeks of anti-TNF treatment with clinical disease activity and treatment response at 26 weeks in clinically active RA patients. Methods: Clinically active RA patients, with arthritis of at least two joints and a indication for initiation of aTNF therapy, were included. Whole body [¹¹C]-DPA713 PET/CT imaging was performed at baseline and after 4 weeks of aTNF therapy. Clinical evaluation was performed at baseline, 4 weeks and 26 weeks to assess the Disease Activity Score of affected joints (DAS44). Using these results, clinical response to aTNF treatment was calculated using the European Alliance of Associations for Rheumatology (EULAR) response criteria. Quantitative PET/CT data (standardized uptake values, SUVs) were extracted from volumes of interest drawn on top of all joints that were also enclosed in the DAS44. The association between SUVs at 0-4 weeks of joint clusters and of total body joints (alone or with added clinical findings) and DAS44 at 26 weeks were compared using linear regression analysis. Subsequently, the most promising SUV 0-4 weeks relating to DAS44 at 26 weeks was explored for its potential diagnostic value for early distinction between responders and non-responders by applying ROC-analyses. Results: Overall patient EULAR response in the 20 included patients to aTNF treatment at 26 weeks was 70% moderate to good. With univariable linear regression analyses, mean metacarpophalangeal (MCP) SUV joint clusters at baseline and at 4 weeks were most strongly associated with DAS 44 at 26 weeks (baseline: R²=0.62, p<0.001, 4 weeks: R²=0.70, p<0.001), and secondly mean of all joints at baseline and at 4 weeks with DAS44 at 26 weeks (baseline: R²=0.52, p<0.001, at 4 weeks: R²=0.49, p=<0.001)(Figure 1). Multivariable analyses using the mean MCP SUV outcome at 4 weeks with addition of the concurrent swollen joint count or C-reactive protein (CRP), improved the predictive value slightly to R²=0.76 and 0.77, respectively. ROC-analysis resulted in optimal value for early determination of aTNF treatment response for the mean MCP SUV of 0,34 at 4 weeks, with an AUC of 0.81, a sensitivity of 83.3%, specificity of 71.4%, PPV of 0.71, NPV of 0.83, and accuracy of 0.75 (Figure 2). Conclusion: Quantitative whole-body macrophage [¹¹C]-DPA713 PET/CT joint imaging at baseline and 4 weeks was significantly associated with clinical status (DAS44) at 26 weeks, and show promise for early prediction of EULAR response to aTNF. Macrophage targeted [¹¹C]-DPA713 PET/CT joint imaging may therefore have value for clinical stratification and early prediction of aTNF treatment efficacy in RA patients. REFERENCES: [1] Kerschbaumer, A. et al., Ann Rheum Dis. 2020;79(6). [2] Smolen, J.S. et al., L Ann Rheum Dis. 2023;82(1). [3] Smolen, J.S. et al., Ann Rheum Dis. 2020;79(6). [4] Udalova, I. et al., Microbiol Spectr. 2016;4(4). [5] Bruijnen, S.T.G. et al., PLoS One. 2019;14(9). [6] Verweij, N. et al., RMD Open. 2022;8(1). Acknowledgements: NIL. Disclosure of Interests: None declared.