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. 2021 Sep 1;60(9):4384-4389.
doi: 10.1093/rheumatology/keaa894.

Use of 18F-fluorodeoxyglucose positron emission tomography to monitor tocilizumab effect on vascular inflammation in giant cell arteritis

Kaitlin A Quinn  1 , Himanshu Dashora  1 , Elaine Novakovich  1 , Mark A Ahlman  2 , Peter C Grayson  1
Affiliations

Use of 18F-fluorodeoxyglucose positron emission tomography to monitor tocilizumab effect on vascular inflammation in giant cell arteritis

Kaitlin A Quinn et al. Rheumatology (Oxford). .

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.

Keywords: giant cell arteritis; large-vessel vasculitis; positron emission tomography; tocilizumab.

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Figures

<sc>Fig</sc>. 1
Fig. 1
18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) findings in response to tocilizumab in GCA Patients underwent FDG-PET scan immediately prior to initiation of tocilizumab and a follow-up FDG-PET scan on tocilizumab treatment. PETVAS (median, IQR), a summary score of arterial FDG-uptake, improved in response to tocilizumab (A). Representative FDG-PET scans prior to (B) and during tocilizumab treatment (C) are shown in a patient with GCA. At the baseline study visit two years after diagnosis, she reported ongoing constitutional symptoms on prednisone 5 mg/day. FDG-PET showed moderate-severe FDG uptake throughout the aorta and arch vessels on whole-body imaging (red arrows) and axial views (blue arrows) (B). She was treated with tocilizumab yet remained on prednisone 5 mg/day. Six months later, she reported clinical improvement coinciding with significant improvement in arterial FDG uptake (C). IQR: interquartile range; PETVAS: PET vascular activity score; TCZ: tocilizumab.
<sc>Fig</sc>. 2
Fig. 2
Longitudinal change in 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) activity during tocilizumab treatment Patients who underwent multiple FDG-PET scans during tocilizumab treatment, continued to have reduction in PETVAS (median, IQR) over a two-year treatment period (A). Of the six patients who discontinued tocilizumab, five had worsening FDG-PET activity on subsequent imaging studies, and two patients experienced a clinical relapse in disease activity (red) (B). Representative FDG-PET scans during tocilizumab treatment (C) and post-tocilizumab treatment (D) are shown in a patient with biopsy-proven GCA treated with tocilizumab. While on treatment, there was minimal FDG uptake throughout the large arteries seen on whole-body and axial views (C). He discontinued tocilizumab after 18 months of therapy due to established clinical remission and subsequently developed fatigue, bilateral arm claudication, and elevations in acute phase reactants (ESR 28 and CRP 10.7 mg/L). A repeat FDG-PET scan off tocilizumab showed increased uptake in the large arteries on whole-body (red arrows) and axial views (blue arrows) (D). IQR: interquartile range; PETVAS: PET vascular activity score; TCZ: tocilizumab.
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