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

Results

Study Population

Out of 74 patients with GCA enrolled in the cohort, 25 patients were treated with tocilizumab after study enrolment. Baseline demographics of the study population are shown in Supplementary Table S1, available at Rheumatology online. The majority of patients were female (76%) with a median age of 70.5 years. All patients had clinically active disease with associated active vasculitis on PET at the baseline visit. One baseline PET scan was excluded from further analyses due to poor quality. Fourteen (56%) patients previously received methotrexate, which was discontinued in all patients when tocilizumab was started.

Assessment of FDG-PET Activity Following Tocilizumab Treatment

Three out of 25 (12%) patients remained clinically active at the most recent follow-up visit despite treatment with tocilizumab. Eleven out of 25 (44%) FDG-PET scans showed persistent active vasculitis by subjective assessment by the reader at the most recent follow-up visit, including the three patients who remained clinically active. The median imaging time interval while on tocilizumab was 1.1 years [interquartile range (IQR) 0.5–1.5 years]. There was significant reduction in PETVAS in response to tocilizumab treatment from the baseline visit (24.0, IQR 22.3–27.0) to the most recent follow-up visit (18.5, IQR 15.3–23.8); P < 0.01 (Figure 1A).

Figure 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.

Fourteen patients were treated with tocilizumab for relapsing disease without substantial concomitant glucocorticoid exposure (i.e. prednisone dose ≤10mg/day during baseline and follow-up scan). Significant reduction in PETVAS was still observed in this subset of patients [25.0, IQR 23.0–27.0–19.0, IQR 16.0–26.0; P = 0.04]. No significant association was found between cumulative glucocorticoid dose and change in PETVAS from baseline to most recent follow-up visit (r = 0.35, P = 0.11). Representative FDG-PET images from a patient treated with tocilizumab without substantial concomitant glucocorticoids are shown (Figure 1B and C).

Longitudinal Change in Disease Activity on FDG-PET

A significant reduction in PETVAS was observed over a two-year treatment period (P < 0.01 for linear trend) (Figure 2A). All 25 patients had follow-up FDG-PET imaging studies after 6 months of tocilizumab treatment with significant improvement in median PETVAS [24.0, IQR 22.3–27.0–21.0, IQR 19.0–24.0; P < 0.01]. Nineteen patients (76%) had follow up FDG-PET imaging studies after 1 year of tocilizumab treatment and 12 patients (48%) had follow up FDG-PET imaging studies after ≥18 months of tocilizumab treatment. Importantly, there was a similar degree of improvement in vascular FDG uptake in both the first and the second years of treatment.

Figure 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.

Six patients discontinued tocilizumab during the study. Five patients discontinued tocilizumab at the discretion of the treating physician after achieving clinical remission, and one patient discontinued due to persistent disease activity. The median time between tocilizumab discontinuation and the FDG-PET scan performed after tocilizumab treatment discontinuation was 0.5 years (IQR 0.5–0.9 years). At the time of tocilizumab discontinuation, the median PETVAS was 18.5 (IQR 16.5–21.0). A repeat FDG-PET scan at least 6 months after treatment discontinuation showed worsening PET activity in five out of six patients (median PETVAS 21.5, IQR 17.3–23.0, P = 0.03) (Figure 2B). Two of the five patients with worsening vascular PET activity subsequently experienced a clinical relapse within 6 months (patient 1: PETVAS increased from 20 to 23; patient 2: PETVAS increased from 18 to 23). The two patients who experienced a clinical relapse were re-started on tocilizumab. The remaining three patients with worsening vascular PET activity without recurrence of clinical symptoms were not re-started on tocilizumab. Representative PET images from a patient who discontinued tocilizumab and subsequently experienced a clinical relapse are shown in Figure 2C and D.

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