Background/Purpose: Two randomized controlled trials have demonstrated the clinical efficacy of tocilizumab for treatment of giant cell arteritis (GCA) (1,2).  In these trials, response to treatment was defined by improvement in clinical and laboratory-based assessment of disease activity, but direct assessment of the large arteries by vascular imaging was not systematically evaluated.

The objective of this study was to evaluate the longitudinal effects of tocilizumab on vascular inflammation as measured by ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in giant cell arteritis (GCA).

Methods: Patients with GCA treated with tocilizumab were selected from an ongoing prospective, observational cohort.  All patients fulfilled modified 1990 American College of Rheumatology (ACR) Classification Criteria for GCA.  Patients underwent FDG-PET computed tomography (CT) at the baseline visit prior to the initiation of tocilizumab and at subsequent follow-up visits.  In a subset of patients in whom tocilizumab was discontinued due to established remission, a repeat FDG-PET scan was obtained after therapy discontinuation.

A single reader reviewed all PET scans, blinded to clinical data.  Qualitative assessment of FDG uptake relative to liver uptake by visual assessment (scale 0-3) was assessed in 9 arterial territories. A summary score, PET Vascular Activity Score (PETVAS), was calculated (scale 0-27).

Wilcoxon signed rank test was used to compare change in PETVAS between study visits.  Linear regression was used to determine change in PETVAS over multiple timepoints.

Results: Twenty-five patients with GCA were included.  All patients had clinically active disease with associated active vasculitis by FDG-PET imaging at the baseline visit.  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 the second years of treatment (Figure). 

In a subset of six patients who discontinued tocilizumab due to established remission [median PETVAS 18.5 (16.5-21.0) at time of remission], a repeat FDG-PET scan at least 6 months after treatment discontinuation showed worsening PET activity in 5 out of 6 patients [median PETVAS 21.5 (17.3-23.0)].  Two of these patients subsequently experienced a 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.  There was continued improvement of vascular inflammation at both year 1 and year 2 of treatment, and this preliminary evidence suggests a rebound of vascular inflammation when tocilizumab was discontinued.  These data support the use of FDG-PET as a novel outcome measure in clinical trials in GCA.

References

1. Stone JH, et al. N Engl J Med 2017;377:317-28.
2. Villiger PM, et al. Lancet 2016;387:1921-7.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/feasibility-of-18f-fluorodeoxyglucose-positron-emission-tomography-to-monitor-the-effect-of-tocilizumab-on-vascular-inflammation-in-giant-cell-arteritis-a-prospective-observational-cohort-study/