Abstract
Background
The proportion of patients with giant cell arteritis (GCA)-related large vessel vasculitis (LVV) treated with tocilizumab (TCZ) who achieve a complete metabolic response on repeated 18 F-fluorodeoxyglucose positron emission tomography (18FDG-PET)-CT (PET/CT) is unknown.
Methods
We conducted a retrospective multicentre study that enrolled patients with GCA-related LVV demonstrated on PET/CT, who were treated with TCZ and underwent at least one repeated PET/CT. The primary endpoint was the proportion of patients with vascular extinction on repeated PET/CT during or after TCZ treatment (grade 0 or 1 on the visual vascular to liver FDG uptake grading scale).
Results
A total of 91 patients (64 women (70%), median age: 69 (54–83) years) were included. Clinical remission and a complete metabolic response on PET/CT were observed in 69 patients (76%). Among these, 30 had discontinued all GCA treatments and had not relapsed after >12 months of follow-up post negative PET/CT; the remaining 39 patients were still treated or had <12 months of follow-up after the negative PET/CT.
13 (14%) patients experienced a relapse of LVV on a third PET/CT within 12 months after TCZ discontinuation. During follow-up, an aortic dilation occurred in one (1%) patient with complete metabolic extinction and in four (18%) patients who did not show complete and persisting PET/CT extinction (p=0.006 by log-rank test).
Conclusion
This study suggests that TCZ is an interesting therapeutic option for achieving complete metabolic response on PET/CT in patients with GCA-related LVV. The subsequent risk of aortic dilation may be reduced.
Keywords: Giant Cell Arteritis, Vasculitis, Treatment
WHAT IS ALREADY KNOWN ON THIS TOPIC.
WHAT THIS STUDY ADDS
TCZ is effective in achieving extinction of metabolic activity on positron emission tomography (PET)/CT.
Patients with persistent metabolic activity on PET/CT during follow-up had an increased risk of developing aortic dilation.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
TCZ may be an effective treatment for patients with GCA-related LVV and PET/CT may be a good imaging tool to monitor treatment efficacy.
This study suggests that PET/CT metabolic extinction under TCZ may be associated with prevention of aortic dilation.
Introduction
Giant cell arteritis (GCA) is the most frequent systemic vasculitis in patients over 50, typically affecting the branches of the external carotid.1 However, inflammation of the aorta and its main branches, that is, large vessel vasculitis (LVV), is also described in 40–50% of patients with GCA.2 Among large-vessel imaging, 18 F-fluorodeoxyglucose positron emission tomography (18FDG-PET)/CT is a sensitive tool to diagnose LVV.3 When compared with patients without LVV, patients with GCA-related LVV had a worse prognosis with a higher risk of relapse and a higher risk of cardiovascular events, notably of aortic dilation.4 Little is known about the predictive factors associated with the occurrence of aortic dilation. Moreel et al showed that patients with a positive PET/CT at diagnosis had a greater increase in thoracic aortic dimensions during follow-up than those with negative imaging findings.5 In addition, the same group reported that patients who developed an aortic dilation were more likely to have persistent vascular uptake on follow-up PET/CT6 and that aortic dilation occurred in the inflamed vascular segments. Conversely, the risk may be reduced in patients with PET/CT extinction under treatment. An additional histological study showed that 80% of patients with a history of inactive GCA (ie, no clinical or biological activity), who were treated surgically for aortic dilation or dissection, showed histological signs of active vasculitis on surgical specimens.7 Altogether, these PET/CT and histological studies suggest that the risk of aortic dilation is increased when aortic inflammation is insufficiently controlled.
Little is known about the best treatment and follow-up of LVV. A limited number of studies analysed LVV outcomes on PET/CT in patients treated with tocilizumab (TCZ), using activity scores to monitor vascular response under treatment (eg, PET Vascular Activity Score (PETVAS) and Total Vascular Score (TVS)).8,19 Most of these studies reported a favourable vascular response to TCZ, with a reduction in the extent and/or intensity of vascular uptake. However, few studies specifically analysed the proportion of patients with complete vascular extinction under treatment. Based on these PET/CT and histological studies, we hypothesise that a complete metabolic response would better reflect vasculitis control—with a greater impact on the risk of aortic dilation—than a reduction in vascular activity scores. We thus conducted this retrospective study to determine the proportion of patients with GCA-related LVV treated with TCZ who achieved a complete metabolic response on repeat PET/CT.
Patients and methods
Study population
This retrospective multicentre study enrolled patients with GCA-related LVV demonstrated on 18FDG-PET/CT between January 2015 and December 2024 and treated with TCZ. Patients were enrolled in the French Study Group for Large Vessel Vasculitis.
To be included in this study, patients had to satisfy the following criteria: (1) a GCA diagnosis, according to the 2022 revised American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria,20 (2) evidence of LVV involving at least two vascular territories on 18FDG-PET/CT at any time during the course of GCA, (3) active GCA treatment with TCZ for at least 3 months after their baseline PET/CT and (4) at least one repeat PET/CT performed >3 months after the first PET/CT to analyse vascular outcomes under TCZ.
In the participating centres, PET/CT is routinely performed at GCA diagnosis and during follow-up to control the evolution of LVV under treatment or in patients with relapsing disease. In addition, in patients with LVV treated with TCZ, PET/CT is systematically repeated during follow-up to assess changes in large-vessel uptake.
Patients who received treatments other than glucocorticoids (GC) and TCZ between repeated PET/CT were excluded from the study.
Studied parameters and definitions
For all included patients, we collected demographics, body mass index, cardiovascular risk factors (ie, hypertension, tobacco use, diabetes mellitus, dyslipidaemia, history of coronary disease or stroke), inflammatory laboratory parameters (ie, fibrinogen and C reactive protein levels), histology results, GC management during the disease course, results of initial and repeated PET/CT, relapses before, during and after TCZ treatment and data regarding TCZ management.
The primary endpoint of this study was the proportion of patients at last follow-up with clinical remission and metabolic extinction, defined as the absence of GCA-related clinical symptoms and a metabolic extinction of large vessels (ie, grade 0 or 1 on the visual vascular-to-liver FDG uptake grading scale) on repeated PET/CT performed during TCZ treatment or within 3 months after TCZ discontinuation. Since non-extensive grade 1 uptakes are frequent in this population (due to atheroma and/or fibrous dysplasia) and considered non-specific, we assumed that a PET/CT with focal grade 1 uptake was considered negative. Sustained remission was defined by a complete metabolic response on repeated PET/CT, a discontinuation of any GCA treatment (eg, TCZ, GC) and at least a 12-month follow-up after the last negative imaging without any further GCA relapse.
Cranial vessels were not evaluated on PET/CT.
For all included patients, every PET/CT available was collected. However, in the final analysis, among the repeated imaging, we only kept two, three or four PET/CT (namely PET/CT 1, 2, 3 and 4). PET/CT 1 was the positive PET/CT closest to TCZ initiation. PET/CT 2 was the last positive imaging before TCZ discontinuation or the first negative PET/CT during TCZ treatment. All patients had a PET/CT 1 and 2. PET/CT 3 was the first positive imaging in a patient with a clinical and/or biological GCA relapse and who previously experienced a metabolic extinction on PET/CT 2 (ie, relapse of LVV on PET/CT). Finally, PET/CT 4 was the repeated PET/CT after LVV relapse if TCZ was used to treat this relapse.
Relapse was defined by a reappearance of GCA-related clinical symptoms and/or increased acute phase reactants.
PET/CT (at diagnosis and follow-up) was performed under standard conditions at each participating centre. PET was combined with a low-dose CT scan in patients with plasma glucose levels below 7 mmol/L. Image acquisition occurred 60–90 min after injection of 18FDG (3 MBq/kg). PET data from patients were reconstructed with a Point Spread Function (PSF)+Time-of-Flight (TOF) reconstruction.
Results from PET/CT were obtained on imaging reports. All PET/CT scans were analysed using the visual grade of FDG uptake. Extensive grade 2 and grade 3 (ie, intensity of vascular metabolisms similar to or superior to the liver metabolism) were considered positive.3 21 On each PET/CT, eight vascular territories were analysed: thoracic and abdominal aorta, subclavian, axillary, carotid arteries, iliofemoral, upper and lower limb arteries.
During follow-up, we recorded the occurrence of aortic dilation in patients with and without metabolic extinction on PET. In accordance with previous reports, the aorta was considered dilated when its diameter was >40 mm for the ascending thoracic aorta and aortic arch, >35 mm for the descending thoracic aorta and >30 mm for abdominal aorta.22
Statistical analyses
Categorical variables are expressed as the number (%) and quantitative variables as the median (IQR). Categorical variables were analysed using χ2 or Fisher’s exact tests, and quantitative variables were analysed using Wilcoxon rank-sum tests. Occurrence of aortic dilation in patients with and without metabolic extinction was analysed using life tables and the Kaplan-Meier method. Comparison was conducted using log-rank tests.
The statistical analyses were conducted using R V.4.4.1 software; p<0.05 defined statistical significance.
Results
A total of 91 patients (64 women (70%), median age at diagnosis: 69 (66–75) years) with GCA-related LVV treated with TCZ were included. TCZ was introduced 20 (10–112) days after PET/CT 1 results. All patients had a median of 4 (3–5) vascular territories involved on PET/CT 1. Their characteristics are described in table 1. The median follow-up was 33 (15–53) months from diagnosis to last follow-up visit and 12 (2–27) months after the last PET/CT. On PET/CT 2, performed 11 (7–14) months after PET/CT 1, 79 (87%) patients had a complete metabolic extinction. Regarding the primary endpoint, at last follow-up, 69 (76%) patients were in clinical remission with metabolic extinction under TCZ, including 30 in sustained remission, 4 without treatment but a follow-up <12 months, and 35 with ongoing GCA-related treatments at last follow-up. In the 30 patients with sustained remission, GCA treatment had been discontinued for a median of 24 (20–40) months at the last follow-up. We did not observe any relevant baseline differences between patients with and without metabolic extinction (table 1).
Table 1. Comparison of baseline characteristics at GCA diagnosis and outcomes of 91 GCA patients with LVV treated with TCZ according to their metabolic response on repeated 18FDG-PET-CT.
| Total n=91 |
Metabolic extinction n=69 |
No metabolic extinction n=22 |
P value | |
|---|---|---|---|---|
| Demographics | ||||
| Female | 64 (70) | 45 (65) | 19 (86) | 0.06 |
| Median age (years) | 69 (66–75) | 70 (65–75) | 69 (66–75) | 0.93 |
| Cardiovascular risk factors | ||||
| Tobacco use | 28 (31) | 23 (33) | 5 (23) | 0.34 |
| Arterial hypertension | 39 (43) | 28 (41) | 11 (50) | 0.44 |
| Diabetes mellitus | 5 (5) | 4 (6) | 1 (5) | 1 |
| Dyslipidaemia | 24 (26) | 18 (26) | 6 (27) | 0.91 |
| History of strokes | 4 (4) | 2 (3) | 2 (9) | 0.25 |
| History of coronary disease | 11 (12) | 10 (14) | 1 (5) | 0.28 |
| Clinical manifestations at baseline | ||||
| Body mass index, kg/m2 | 24.2 (21.5–27.1) n=49 |
24.2 (21.5–26.4) n=33 |
23.9 (21.5–28.4) n=16 |
0.69 |
| Cranial manifestations | 65 (71) | 49 (71) | 16 (73) | 0.87 |
| Ophthalmic involvement | 14 (15) | 9 (13) | 5 (23) | 0.31 |
| Limb claudication | 6 (7) | 4 (6) | 2 (9) | 0.63 |
| Polymyalgia rheumatica | 50 (55) | 40 (58) | 10 (45) | 0.30 |
| Diagnosis of LVV on PET/CT | ||||
| GCA and LVV diagnosed concomitantly | 65 (71) | 52 (75) | 13 (59 | 0.14 |
| Elapsed time in others, months | 8.5 (6–15) | 8.5 (6–13.5) | 8 (6–16) | 0.89 |
| Laboratory tests, at baseline | ||||
| Fibrinogen, g/L | 6.8 (4.7–8) n=34 |
7 (4.5–8) n=24 |
7 (5–7.6) n=10 |
0.82 |
| C reactive protein, mg/L | 79 (40–134) n=78 |
85 (39–132) n=60 |
76 (38–141) n=18 |
0.87 |
| Haemoglobin, g/L | 112 (104–122) n=57 |
113 (104–123) n=43 |
111 (97–120) n=14 |
0.72 |
| Positive histology | 53/77 (69) | 37/55 (67) | 16/20 (80) | 0.28 |
| GC management | ||||
| GC doses at onset, mg/day | 45 (40–60) | 45 (40–60) | 50 (40–60) | 0.58 |
| GC discontinuation at last FU | 72 (79) | 61 (88) | 11 (50) | 0.0003 |
| Elapsed time to GC discontinuation, months | 12 (10–18) | 12 (9–16.5) | 18 (13–30) | 0.02 |
| Median GC dose at last FU in others, mg/day | 5 (4–12) | 5 (1–7) | 5 (5–15) | 0.81 |
| TCZ management | ||||
| Use of any IS before TCZ | 16 (18) | 10 (14) | 6 (27) | 0.20 |
| TCZ start at GCA diagnosis | 38 (45) | 31 (45) | 7 (32) | 0.28 |
| Elapsed time in others, months | 13 (8–20) | 13 (9–19) | 14 (6–24) | 0.86 |
| Discontinuation of TCZ at last follow-up | 46 (51) | 41 (59) | 5 (23) | 0.003 |
| Duration of TCZ in those who stop | 14 (12–20) | 14 (12–20) | 13 (11–21) | 0.47 |
| GCA relapses | ||||
| Any GCA relapse | 58 (64) | 38 (55) | 20 (91) | 0.002 |
| Any GCA relapse before TCZ | 54 (55) | 38 (55) | 16 (73) | 0.21 |
| LVV relapse after TCZ | 13 (16) | 3 (4) | 10 (45) | <0.0001 |
| Death | 2 (2) | 2 (3) | 0 (0) | 1 |
| Follow-up (months) | 33 (15–53) | 32 (14–48) | 46 (17–60) | 0.21 |
| Time between PET/CT 1 and 2, months | 11 (7–14) | 11 (7–14) | 12 (7–15) | 0.43 |
| Follow-up after last PET/CT, months | 12 (2–27) | 15 (3–31) | 9 (0–16) | 0.08 |
Values are numbers (%) or medians (IQR).
FU, follow-up; GC, glucocorticoids; GCA, giant cell arteritis; IS, immunosuppressants; LVV, large vessel vasculitis; PET, positron emission tomography; TCZ, tocilizumab.
At last follow-up, among the 69 patients with metabolic extinction, 3 experienced a relapse of LVV (on PET/CT 3) and were retreated with TCZ, resulting in a new metabolic extinction (on PET/CT 4). In these 3 patients, relapse occurred 6, 8 and 11 months after TCZ discontinuation, and none were receiving GC at the time of relapse. At the last follow-up, all three patients were in remission, including two in sustained remission.
In the 22 patients without metabolic extinction at last follow-up, 10 (11%) had achieved previous metabolic extinction but with a subsequent LVV relapse on PET/CT 3, 9 (10%) showed no vascular improvement between repeated PET/CT and 3 (3%) showed a reduction in vascular uptake without complete extinction. For the 10 patients who relapsed, relapse occurred after they discontinued TCZ for a median of 16 (12–24) months. At last follow-up, these 10 patients were receiving TCZ without GC, except for one patient. Five of them underwent a PET/CT 4, at a median of 8 months (7–10) after TCZ resumption. In all five, PET/CT 4 showed a reduction in vascular metabolic activity without complete extinction (online supplemental figure 1). In the nine patients without metabolic improvement, PET/CT showed a median of 3 (3–4) inflamed territories. The aorta was involved in all nine patients, including the thoracic section in four and the abdominal section in five patients. Aortic branches were also involved in all patients: subclavian arteries were involved in four patients, axillary arteries in two, carotid arteries in five, iliofemoral arteries in five, upper limb arteries in one and lower limb arteries in two patients. In the three patients with metabolic improvement, PET/CT initially showed 4, 4 and 5 involved territories, respectively. Under treatment, uptake disappeared in the carotid arteries in two patients and in the subclavian arteries in one patient. Persistent uptake remained in the thoracic aorta in two patients, the abdominal aorta in two patients and the iliofemoral arteries in two patients.
Altogether, among the 79 patients who showed a metabolic extinction on PET/CT 2, 24 (30%) patients experienced a GCA relapse during follow-up, including 13 (16%) with an LVV relapse on PET/CT 3 (ie, the 3 patients who were in clinical and metabolic remission at last follow-up and the 10 patients without metabolic extinction at last follow-up). All patients with LVV relapses resumed TCZ treatment and achieved a clinical remission.
Figure 1 illustrates patient outcomes according to whether TCZ was introduced within 3 months of a positive PET/CT. Among the 91 patients, 66 (73%) were treated with TCZ within the first 3 months after PET/CT 1. Of these, 53 (80%) patients achieved complete metabolic extinction on PET/CT 2 (sustained remission (n=20), remission with ongoing treatment (n=24) and remission without treatment (n=9)) while 13 (20%) patients had persistent positive PET/CT positivity. We did not observe any differences regarding baseline characteristics and therapeutic management between these two groups (data not shown). In contrast, among the 25 (27%) patients who received TCZ more than 3 months after positive PET/CT 1, 16 (64%) achieved complete metabolic extinction on PET/CT 2, including 10 (62%) in sustained remission.
Figure 1. Metabolic response on 18FDG-PET-CT and treatment outcomes of 91 GCA patients with LVV treated with TCZ according to the delay of TCZ initiation. 18FDG-PET-CT, 18-F-fluorodeoxyglucose positron emission tomography/computed tomography; FU, follow-up; GCA, giant cell arteritis; LVV, large vessel vasculitis; TCZ, tocilizumab.
Outcomes did not differ according to the localisation of LVV on PET/CT 1 (table 2).
Table 2. Comparison of PET/CT vascular involvement at baseline according to the metabolic status at last follow-up.
| Metabolic extinction n=69 |
No metabolic extinction n=22 |
|
|---|---|---|
| Number of involved vascular territories | 5 (4–5) | 4 (3–5) |
| Involved vascular territories | ||
| Thoracic aorta | 52 (75) | 14 (64) |
| Abdominal aorta | 54 (78) | 16 (73) |
| Subclavian arteries | 40 (58) | 10 (45) |
| Axillary arteries | 20 (29) | 5 (23) |
| Carotid arteries | 60 (87) | 17 (77) |
| Iliofemoral arteries | 20 (29) | 7 (32) |
| Upper limb arteries | 5 (7) | 1 (5) |
| Lower limb arteries | 5 (7) | 2 (9) |
Values are numbers (%) or medians (IQR).
PET/CT, positron emission tomography/computed tomography.
During follow-up, five patients developed thoracic aortic dilation, including four (18%) patients who had not achieved metabolic extinction on the last PET/CT (p=0.01). The patient with metabolic extinction who developed a dilation had previously shown inflammation of the thoracic aorta. The cumulative incidence of aortic dilation in patients with and without metabolic extinction on repeated PET/CT is shown in figure 2 (p=0.01 by log-rank test).
Figure 2. Cumulative incidence of aortic dilations in giant-cell arteritis patients with and without metabolic extinction of PET/CT. Patients without metabolic extinction on repeated PET/CT showed more aortic dilations than patients with. The log-rank test was used to calculate the statistical difference between both groups.
Four additional patients, who were in remission at last follow-up, had an aortic dilation at diagnosis, with no progression observed during follow-up.
Discussion
This study highlights that approximately three-quarters of patients with GCA-related LVV treated with TCZ achieved a complete metabolic response on repeated PET/CT. No PET/CT-documented relapse was observed during TCZ treatment. However, 14% of patients experienced LVV relapse >6 months after TCZ discontinuation.
To our knowledge, this is the largest study analysing GCA-related LVV treated with TCZ and evaluating the rate of complete metabolic response on PET/CT. In line with the findings of Blockmans et al,6 we observed more aortic dilations in patients with persistent PET/CT positivity.
In LVV patients treated with TCZ, PET/CT may be useful for monitoring therapeutic response and adapting the treatment, especially since inflammatory biomarkers commonly used to monitor GCA activity may be misleading under TCZ. Centres that participated in this study routinely use PET/CT in the follow-up of GCA patients with LVV, explaining why most patients treated with TCZ for LVV underwent repeated PET/CT.
In contrast to most studies evaluating TCZ in LVV, we deliberately chose a different but more stringent approach to assess TCZ efficacy, considering that only complete metabolic extinction on PET/CT was a therapeutic success. We did not rely on vascular activity scores such as PETVAS or TVS, as a reduction in these scores under treatment may indicate only a partial therapeutic response if the score does not reach the minimal level.
Among studies analysing the evolution of vascular scores under TCZ, most reported an improvement during treatment, but with a tendency for relapse after treatment discontinuation. In addition, most available data come from small cohorts (often less than 30 patients), with limited follow-up PET/CT assessments and short follow-up durations. Data addressing complete metabolic response on PET/CT are scarce and heterogeneous.
Our results are in line with several previous studies. In the RIGA study, 68.4% of the 19 LVV-GCA patients treated with TCZ in combination with GC achieved PET/CT extinction during a median follow-up of 11.8 months.9 Regola et al showed treatment efficacy in 24 GCA patients with LVV treated with TCZ, with only 1 patient showing persistent metabolic activity higher than liver uptake on follow-up PET/CT.10 In the study by Sebastian et al, out of 10 patients with a positive PET/CT prior to starting TCZ, 9 were in remission after TCZ introduction and 4 showed significant improvement on follow-up imaging.11 In another Italian study, Tomelleri et al found that among 14 patients with a positive PET/CT at the start of TCZ treatment, 86% had a metabolic response at 12 months and 100% at 24 months.12 However, they noted a global relapse rate of 26% on treatment discontinuation. Similarly, in the TOPAZIO study by Muratore et al, which included GCA patients treated with an ultra-short GC treatment and TCZ, 10/16 (62%) PET/CT were negative at week 24 and 10/13 (77%) at week 52.13 In the extension of this study, PETVAS scores increased at week 78 (6 months after TCZ discontinuation) with 35% of patients in clinical relapse by that time and 53% relapsing at 148 weeks after TCZ discontinuation.14 In our study, we observed a low LVV relapse rate (14%) after metabolic extinction. This finding should be interpreted with caution as the median follow-up after a negative PET/CT was 12 months, which may be insufficient to capture further relapses.
On the other hand, some studies have shown disappointing results with TCZ in LVV. Banerjee et al reported that only 3/17 (17%) patients with LVV achieved metabolic extinction at 6 months.15 Quinn et al found that among 25 patients with a positive PET/CT treated with TCZ, 11 (44%) still had a positive PET/CT at follow-up, with a median interval of 1.1 years between scans.16 In a subsequent prospective cohort of 31 patients, the same group observed imaging improvement under TCZ in only 48% of patients during follow-up.17 Prieto Peña et al reported in an initial study of 30 patients with LVV a significant improvement in vascular scores under TCZ, but complete imaging extinction was seen in only 10% of patients, despite clinical remission in 83%.18 In this study, 86.7% of patients were refractory and had previously been treated with high doses of GC alone or in combination with immunosuppressive therapy. In a more recent study from the same Spanish team, complete metabolic extinction was reported in only 24.1% of GCA patients with LVV treated with TCZ at treatment initiation, with follow-up PET/CT performed in 56.1% and 21.6% of patients at 12 and 24 months, respectively.19 Notably, among all patients with a positive PET/CT at TCZ initiation, only 50% underwent follow-up imaging during treatment and the majority of patients who received TCZ were initially refractory to standard treatment (GC).
Our study questions the role of TCZ in the treatment of GCA-related LVV, which currently varies across clinical guidelines. In the American guidelines, experts recommend the use of an immunosuppressant in combination with GC to treat LVV, in order to reduce GC exposure.23 In contrast, according to the 2024 French guidelines, the presence of LVV should not modify the therapeutic strategy due to the lack of available data demonstrating the superiority of TCZ over GC to treat LVV; consequently, TCZ use is mainly restricted to patients in whom a GC-sparing strategy is required.24
Our study has several limitations, especially its retrospective design, which may have led to missing data. Although follow-up was prolonged for some patients, it did not allow us to determine precisely whether prolonged PET/CT extinction reduces the risk of aortic dilation. Nevertheless, we observed a higher incidence of aortic dilation in patients who did not achieve complete PET/CT extinction, confirming findings from the study by Blockmans et al.6 In addition, the binary approach used to distinguish PET/CT outcomes may have led to misclassify some patients, especially those with PET/CT improvement without complete extinction. For example, in the poor-outcome group, 10 patients initially achieved PET/CT extinction but subsequently relapsed after discontinuing TCZ; among them, 5 did not undergo follow-up PET/CT while on treatment at last follow-up, which could have led to them being reclassified into the remission group. No central reviewing of PET/CT was organised and readers were not blinded to clinical or biological data. However, nuclear physicians involved in the analysis of PET/CT in the participating centres were familiar with LVV imaging. As PET/CT was performed across multiple centres, minor variations in imaging protocols may have occurred. The significance of grade 1 vascular uptake is unknown. By convention, such uptake was considered negative. Moreover, this study did not include a control group treated with GC alone or in combination with another steroid-sparing agent. The indication for TCZ initiation may also have introduced selection bias, as treatment was often started for relapsing disease or preferentially prescribed for patients with LVV in participating centres. The real-life setting may have contributed to heterogeneity in timing between assessments (eg, between PET/CT and clinical visits leading to a therapeutic modification). Aorta calibres were not recorded in the dataset, precluding the collection of precise numerical measurements, especially in patients with aortic dilation. Finally, regarding the significant reduction in GC use observed in patients in remission, there was possibly a bias related to the absence of blinding to PET/CT results, which may have potentially led clinicians to prolong GC treatment in patients with persistent metabolic activity.
In conclusion, this study suggests that TCZ may be a valuable option for the treatment of LVV and for achieving metabolic remission on repeated PET/CT. More aortic dilations occurred in patients who did not show extinction of large-vessel uptake. Further studies are required to determine whether patients with LVV should be managed with specific therapeutic strategies and whether PET/CT metabolic extinction should be considered a therapeutic goal.
Supplementary material
Acknowledgements
The authors thank Alison Johnson-de Boysson for English proof reading.
The authors confirm that artificial intelligence (AI) and AI-assisted technologies were not used in the writing process.
Footnotes
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent for publication: Not applicable.
Ethics approval: This study was conducted in compliance with good clinical practices and Declaration of Helsinki principles. At the time of this study and in accordance with French public health law (Art. L 1121–1-1, Art. L 1121–1-2), formal approval from an ethics committee was not required for this type of observational study.
Data availability statement
Data are available upon reasonable request.
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Data Availability Statement
Data are available upon reasonable request.