Effect of Treatment on Imaging, Clinical, and Serologic Assessments of Disease Activity in Large-vessel Vasculitis

Abstract

Objective: Disease activity in large-vessel vasculitis (LVV) is traditionally assessed by clinical and serological variables rather than vascular imaging. This study determined the effect of treatment on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) vascular activity in relation to clinical- and serologic-based assessments.

Methods: Patients with giant cell arteritis (GCA) or Takayasu arteritis (TA) were prospectively evaluated at 6-month intervals in an observational cohort. Treatment changes were made at least 3 months before the followup visit and categorized as increased, decreased, or unchanged. Imaging (FDG-PET qualitative analysis), clinical, and serologic (erythrocyte sedimentation rate, C-reactive protein) assessments were determined at each visit and compared over interval visits.

Results: Serial assessments were performed in 52 patients with LVV (GCA = 31; TA = 21) over 156 visits. Increased, decreased, or unchanged therapy was recorded for 36-, 23-, and 32-visit intervals, respectively. When treatment was increased, there was significant reduction in disease activity by imaging, clinical, and inflammatory markers (p ≤ 0.01 for each). When treatment was unchanged, all 3 assessments of disease activity remained similarly unchanged over 6-month intervals. When treatment was reduced, PET activity significantly worsened (p = 0.02) but clinical and serologic activity did not significantly change. Treatment of GCA with tocilizumab and of TA with tumor necrosis factor inhibitors resulted in significant improvement in imaging and clinical assessments of disease activity, but only rarely did the assessments both become normal.

Conclusion: In addition to clinical and serologic assessments, vascular imaging has potential to monitor disease activity in LVV and should be tested as an outcome measure in randomized clinical trials.

Keywords: FLUORODEOXYGLUCOSE; GIANT CELL ARTERITIS; LARGE-VESSEL VASCULITIS; POSITRON EMISSION TOMOGRAPHY; TAKAYASU ARTERITIS; VASCULITIS.

Figure 1. Changes in imaging, clinical, and serologic measurements of disease activity following treatment among patients with large-vessel vasculitis (giant cell arteritis or Takayasu’s arteritis).

PET scan activity as measured by the Positron Emission Tomography Vascular Activity Score (PETVAS) significantly improved over 6-month intervals following increased treatment, remained unchanged when there was no change in treatment, and significantly worsened following decreased treatment (Panel A). Clinical disease activity, as measured by the physician global assessment (PGA), and serologic activity, as measured by C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), significantly improved in response to increased treatment but did not significantly change over 6-month intervals when treatment was not changed or was decreased (Panels B-D). Note: overlapping data points from different patients may occur in this figure.

Figure 2.. Change in FDG-PET scan activity and clinical activity following increased treatment in large-vessel vasculitis.

Of 36 instances where treatment was increased in the interval between study visits, PET activity was observed in 30 (80%) baseline assessments and clinical activity in 25 (69%) baseline assessments. Following an increase in treatment, PET activity remained present in 24 (67%) of the 6-month follow-up assessments and clinical activity persisted in 14 (39%) of the 6-month follow-up assessments.

Figure 3.. Changes in measures of disease activity in large-vessel vasculitis in response to specific treatments.

PET activity (PETVAS), clinical activity (PGA), and serologic activity (CRP, ESR) all significantly improved in 17 patients with giant cell arteritis who were treated with tocilizumab over a 6-month interval (Panel A). PET activity and clinical activity, but not serologic activity, significantly improved in seven patients with Takayasu’s arteritis treated with infliximab (Panel B). Note: overlapping data points from different patients may occur in this figure.

Figure 4.. An example of a patient with giant cell arteritis with improvement in vascular inflammation as measured by FDG-positron emission tomography following initiation of treatment with tocilizumab.

A 72 year-old woman with large-vessel giant cell arteritis presented for initial evaluation 2 years into disease course on prednisone 5mg/day. She reported fatigue, malaise, and chronic limb claudication. Physician global assessment = 2. Levels of acute phase reactants were normal (ESR=8mm/hr; CRP=0.5mg/L). FDG-PET computed tomography imaging showed moderate/severe FDG uptake (green/red) throughout the aorta and arch vessels (PETVAS=27). Panel A (baseline visit) shows whole body imaging with axial view inset demonstrating PET activity in the ascending and descending aorta. The patient was treated with tocilizumab 162mg every other week and prednisone 5mg/day was continued without a change in dose. At the follow-up visit 6 months later, there was substantial improvement, but not complete normalization, of arterial FDG uptake (PETVAS=24). Panel B (follow-up visit) shows whole body imaging with axial view inset showing improved but persistent PET activity in the ascending and descending aorta.

Figure 5.. Example of a patient with Takayasu’s arteritis with improvement in vascular inflammation as measured by FDG-positron emission tomography following initiation of treatment with tumor necrosis factor inhibitor and methotrexate.

A 15 year-old girl with Takayasu’s arteritis presented for initial evaluation 1 year into disease course on tocilizumab 162mg every other week and prednisone 10mg/day. She reported ongoing headaches, visual disturbance, postural light-headedness, fatigue, malaise, and abdominal pain. The physician global assessment = 8 and the levels of acute phase reactants were normal (ESR=4mm/hr; CRP=0.2mg/L). FDG-PET magnetic resonance imaging showed moderate (green) to severe (red) FDG uptake with associated increased wall thickness in the abdominal aorta (Panel A, white arrows) and carotid arteries (Panel B, white arrows) with PETVAS score of 15. Tocilizumab was discontinued and she was treated with infliximab, methotrexate, and increasing doses of glucocorticoids. At the follow-up visit 6 months later on infliximab 7.5mg/kg every 4 weeks, methotrexate 20mg weekly and prednisone 20mg daily, there was substantial reduction in vascular wall thickness on angiography and normalization of FDG-PET activity (PETVAS = 10) in the abdominal aorta (Panel C, white arrows) and carotid arteries (Panel D, white arrows).