OP0189\u2005MACROPHAGE PET/CT IMAGING OF THE FEET CAN CONTRIBUTE TO EARLY PREDICTION OF THERAPY OUTCOME IN RHEUMATOID ARTHRITIS

Abstract

Treat-to-target strategies for rheumatoid arthritis (RA) have shown significant improvements in therapy outcomes. Nevertheless, it usually takes a minimum of 12 weeks before clinical assessment of treatment response can be made. Quantitative positron emission tomography (PET) has shown potential to predict clinical response at a very early stage in the treatment in RA patients.(1) In particular, macrophage imaging by [11C]-(R)-PK11195 PET allows for highly sensitive and specific imaging of RA disease activity.(2,3)To determine whether quantitative assessment using [11C]-(R)-PK11195 PET/CT imaging at 0-2 weeks is associated with subsequent clinical response to therapy with methotrexate and step-down prednisolone (COBRA-light) therapy in therapy-naive RA patients.Whole body [11C]-(R)-PK11195 PET/CT scans were performed at baseline and after two weeks of treatment in thirty-five clinically active and therapy-naive RA patients and at least two clinically inflamed joints. All patients were DMARD-naïve and received medication according to the COBRA-light schedule. (4) Clinical follow up with DAS44 assessment was performed at 0, 2 and 13 weeks of treatment. PET/CT scans were visually assessed by two experienced readers blinded to clinical data and quantitatively analyzed using in-house software. Regions of interest (ROIs) with a fixed size per joint (on both visual PET positive and negative joints) were placed on shoulders, elbows, hips, knees and hand and feet joints, with the CT-scan as anatomical reference. Standardized uptake values (SUVs) normalized for body weight were calculated in these ROIs to determine the amount of tracer uptake per joint. SPSS version 22.0 was used to perform regression analyses. The sum of visually positive joints and the average SUV in hand joints, feet joints and all joints in the body were compared with DAS44 scores.Included patients were mostly male (51%) and aged 54 ± 12. Baseline DAS44 was 3.2 ± 1.0; all but one of the thirty-five patients demonstrated visually enhanced tracer uptake in one or more joints on PET/CT. A total of 171 (out of 1470) joints (12%) were visually PET positive at baseline. Over 90% of PET positive sites were located either in the wrists (15%), small hand joints (37%), or small feet joints (40%; Figure 1A). After 2 weeks, the number of PET positive joints had decreased to 100, with the highest decrease in quantitative uptake in feet joints (Figure 1B). Notably, both visual and quantitative PET data at baseline and differences between baseline and 2 weeks did not correlate with DAS44 at 13 weeks (DAS44-13wks). However, at 2 weeks, the average SUV in the feet (SUVfeet-2wks) – but not average SUVhands-2wks or average SUVtotalbody-2wks – was significantly correlated with DAS44-13wks (R2 = 0.14, p = 0.04). DAS44-2wks and SUVfeet-2wks both contributed independent information to the prediction DAS44-13wks (combined R2 = 0.297, p < 0.01).Figure 1.Changes in [11C]-(R)-PK11195 uptake in MTP joints of a RA patient, before (A) and 2 weeks after initiation of COBRA light treatment (B).Quantitative macrophage PET assessment in feet joints after 2 weeks of COBRA light treatment in early RA patients correlates with clinical response after 3 months of treatment. This correlation further increases when combined with the DAS44 score at 2 weeks. Therefore, quantitative, non-invasive macrophage PET/CT, especially when combined with early clinical assessment, may be useful for early assessment of response to treatment. Further studies will help optimize timing and focus of the PET examination in prediction of treatment response.[1]Elzinga EH, et al. J Nucl Med. 2011; 52(1):77-80.[2]Van der Laken CJ et al. Arthritis Rheum. 2008 Nov;58(11):3350-5.[3]Gent YY, et al. J Rheumatol. 2014; 41: 2145-52[4]Den Uyl D, et al. Ann Rheum Dis. 2014;73(6):1071-8.Nicki J.F. Verweij: None declared, Marieke ter Wee: None declared, Jerney de Jongh: None declared, Gerben C.J. Zwezerijnen: None declared, Maqsood Yaqub: None declared, Dirkjan van Schaardenburg: None declared, Alexandre Voskuyl: None declared, WIllem Lems Speakers bureau: Pfizer, Galapagos, Eli Lilly, Amgen, UCB, Curaphar, Consultant of: Pfizer, Galapagos, Eli Lilly, Amgen, UCB, Curaphar, Grant/research support from: Pfizer, Adriaan A. Lammertsma Consultant of: Roche, Maarten Boers Consultant of: Novartis, BMS, Pfizer, Conny J. van der Laken Consultant of: Novartis, Pfizer, Abbvie, UCB, BMS, GSK, Galapagos, Grant/research support from: Novartis, Pfizer, Abbvie, UCB, BMS, GSK, Galapagos