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ACR 2017 | Daily Highlights
Assessment of Treatment Response By 18f-Fludeoxyglucose Positron Emission Tomography (FDG-PET) in Patients with Large Vessel Vasculitis (LVV)
Authors: Shubhasree Banerjee1, Sara Alehashemi2, Ali Cahid Civelek3, Elaine Novakovich4, Armin Bagheri5, Ashkan Malayeri3, Mark Ahlman3 and Peter C. Grayson6, 1Fellowship and training branch, NIAMS/NIH, Bethesda, MD, 2Rheumatology, National Institutes of Health, Bethesda, MD, 3Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, 4Systemic Autoimmunity Branch, NIAMS, National Institutes of Health, Bethesda, MD, 5Vasculitis Translational Research Program, NIAMS, NIH, Bethesda, MD, 6Research, National Institutes of Health, Bethesda, MD
Disease activity in large vessel vasculitis (LVV) is traditionally assessed by clinical and serological (ESR, CRP) parameters. Imaging assessment, including FDG-PET, may also be useful to monitor LVV. The study objective was to determine if currently available therapies for LVV impact disease activity as assessed by clinical, serologic, and imaging-based parameters.
Patients with giant cell arteritis (GCA) or Takayasu’s arteritis (TAK) were recruited into a prospective, observational cohort. All subjects in this study underwent ≥2 FDG-PET/CT scans at 6-month intervals. Serologic assessment (ESR, CRP), clinical assessment [physician global assessment (PGA)] and imaging assessment (PETVAS) was determined at each visit. PETVAS is a global summary score of arterial FDG uptake assessed qualitatively relative to liver activity in 9 vascular beds with higher scores indicating more vascular inflammation. Clinical and imaging assessments were performed blinded to each other. Treatment status between visits was categorized as increased, decreased, or unchanged. Treatment change was defined as change in daily prednisone by ≥5mg or addition/50% dose change of a DMARD or biologic therapy. Paired Wilcoxon test was used to compare changes in PETVAS, ESR, CRP and PGA with change in overall therapy and with addition/increase in specific medications.
FDG-PET/CT was performed in 33 patients with LVV (GCA=21; TAK=12) over 98 visits. Interval treatment changes involved glucocorticoids (n=32), methotrexate (n=13), tocilizumab (n=7), TNF inhibitors (n=7), or another DMARD/ biologic (n=6). Increased, decreased, or unchanged therapy was recorded over 27, 13, and 23 visit intervals respectively. There was simultaneous glucocorticoid reduction with DMARD increase over 2 intervals, which were excluded from analysis. In the increased treatment group, a significant reduction in PETVAS score (p<0.01), inflammatory markers (p<0.01) and PGA (p=0.01) was noted. In the decreased treatment group, PETVAS scores increased (p=0.05) but there was no change in ESR (p=0.3), CRP(p=0.2), or PGA (p=0.28). In the unchanged treatment group, PETVAS (p=0.88), ESR (p=0.8), CRP (p=0.6) and PGA (p=0.48) remained unchanged. In terms of specific therapies, addition of tocilizumab, resulted in significant reduction in PETVAS (p=0.01), acute phase reactants (p=0.01) and PGA (p=0.03), whereas TNF inhibitors and methotrexate addition/dose increase had variable effects on clinical, serological, and imaging parameters.
Similar to clinical and serologic assessment, vascular inflammation assessed by FDG-PET improves with increased treatment and is stable without change in therapy. Unlike clinical and serological assessment, which did not change with reduction in treatment over a 6 month interval, vascular inflammation assessed by FDG-PET worsens with decreased therapy. Specific medications may affect vascular FDG uptake differently. These findings suggest that FDG-PET is useful to monitor treatment response and may be a more sensitive biomarker to detect disease recurrence in the setting of treatment reduction compared to clinical and serologic assessment.
S. Banerjee, None; S. Alehashemi, None; A. C. Civelek, None; E. Novakovich, None; A. Bagheri, None; A. Malayeri, None; M. Ahlman, None; P. C. Grayson, None.
Another central question regarding imaging of large vessel vasculitis addresses the performance of PET in monitoring disease activity. In this study, 33 patients (21 suffering from GCA and 12 from Takayasu-arteritis) were analysed using PET at start and after 6 months of treatment. Disease activity was assessed using the PETVAS. Patients were treated with glucocorticoids, methotrexate, TNF-inhibitors and/or tocilizumab. The authors describe an increase in PET signal intensity if medication was reduced, furthermore they identified differences as a function of treatment modality. Unfortunately, they only show correlations, however, no data regarding prediction of disease progress. In conclusion, it remains advisable to use an imaging method to monitor disease damage, but imaging should not be used as a basis to prescribe treatment.
Eine weitere zentrale Frage an die Bildgebung ist die Performance im Monitoring der Krankheitsaktivität. Diese PET-Studie geht diesem Problem nach. Es wurden 33 Patientinnen, 21 mit GCA und 12 mit TAK prospektiv im Abstand von 6 Monaten mit zweimal mit PET untersucht. Die Krankheitsaktivität wurde mittels PETVAS quantifiziert. Patienten wurden mit Glucokorticoiden, Methotrexat, TNF-Hemmer und Tocilizumab behandelt. Die Autoren beschreiben eine Zunahme des PET Signals bei Reduktion der Medikation und ferner medikamenten-spezifische Unterschiede. Letztlich werden aber nur Korrelationen gezeigt. Entscheidend wäre jedoch ein Mehrwert durch die Bildgebung. Die Bildgebung müsste eine subklinische Aktivität zeigen, die hilft die Therapie zu dosieren. Für den Alltag empfiehlt es sich damit weiterhin, die Bildgebung in die Beurteilung miteinzubeziehen, aber beim Therapieentscheid nicht allein darauf abzustellen.
Prof. Dr. Peter Villiger