Use of 18F-fluorodeoxyglucose Positron Emission Tomography to Monitor Tocilizumab Effect on Vascular Inflammation in Giant Cell Arteritis

Kaitlin A. Quinn; Himanshu Dashora; Elaine Novakovich; Mark A. Ahlman; Peter C. Grayson

Disclosures

Rheumatology. 2021;60(9):4384-4389. 

In This Article

Abstract and Introduction

Abstract

Objectives: To evaluate the time-dependent effects of tocilizumab on vascular inflammation as measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in GCA.

Methods: Patients with GCA treated with tocilizumab were selected from a prospective, observational cohort. Patients underwent FDG-PET at the baseline visit prior to initiation of tocilizumab and at subsequent follow-up visits performed at 6-month intervals. All imaging findings were interpreted blinded to clinical data. The PET vascular activity score (PETVAS) was used to quantify arterial FDG uptake. Wilcoxon signed rank test was used to compare change in PETVAS between visits. Linear regression was used to determine change in PETVAS over multiple timepoints.

Results: Twenty-five patients with GCA were included. All patients had physician-determined active vasculitis at the baseline visit by clinical assessment and FDG-PET interpretation. PETVAS was significantly reduced in association with tocilizumab treatment from the baseline to the most recent follow-up visit [24.0 (IQR 22.3–27.0) vs 18.5 (IQR 15.3–23.8); P <0.01]. A significant reduction in PETVAS was observed over a two-year treatment period (P <0.01 for linear trend), with a similar degree of improvement in both the first and second years of treatment. Repeat FDG-PET scans after tocilizumab discontinuation showed worsening PET activity in five out of six patients, with two patients subsequently experiencing clinical relapse.

Conclusion: Treatment of patients with GCA with tocilizumab was associated with both clinical improvement and reduction of vascular inflammation as measured by serial FDG-PET. Future clinical trials in GCA should study direct treatment effect on vascular inflammation as an outcome measure.

Introduction

Assessment of disease activity in GCA presents several challenges. Because symptoms of GCA are often non-specific (e.g. headache, malaise), clinical assessment of disease activity can be difficult and subjective.[1] Acute phase reactants may or may not track with disease activity, especially in the later phases of disease, and treatments may directly impact laboratory values independent of clinical effect.[2] While glucocorticoids have traditionally been the mainstay of treatment for GCA,[3] two recent randomized controlled trials have demonstrated clinical efficacy of tocilizumab as a steroid-sparing agent.[4,5] In both of these trials, response to treatment was defined by improvement in clinical and laboratory-based assessment of disease activity. Direct assessment of the large arteries by vascular imaging was not systematically studied as an outcome measure in either trial. Accordingly, the direct effect of tocilizumab on vascular inflammation and the utility of vascular imaging as an objective outcome measure in clinical trials of GCA has not been well characterized.

18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a diagnostic imaging modality in GCA that can be used to detect abnormal metabolic activity within the walls of large arteries as a surrogate for vascular inflammation.[6] Few studies have examined the utility of FDG-PET to monitor response to glucocorticoid-sparing treatments in GCA.[7–9] The objective of this study was to evaluate the time-dependent effects of tocilizumab on vascular inflammation as measured by FDG-PET in an observational cohort of patients with GCA. A more direct understanding of the effects of tocilizumab on vascular inflammation could inform treatment recommendations in GCA and impact future clinical trial designs in large-vessel vasculitis.

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