Table 3.
Main findings in cross-sectional studies on hybrid imaging for monitoring of treatment response
| Study | No. of patients and disease stage | Disease duration since diagnosis | Assessment of disease activity | Treatment during scan | FDG uptake during treatment |
|---|---|---|---|---|---|
| Alibaz-Oner et al. (2015)a |
TAK (n = 14) Unclear |
Mean 5.7 years (SD 5) | Physician’s global assessment | Oral methylprednisolone (n = 13), AZA (n = 7), MTX (n = 4), LEFL (n = 2), anti-TNF (n = 3) |
Scan in patients with persistent acute phase response without signs/symptoms of clinically active disease (n = 14) • Vascular FDG uptake grade ≥ 2† found in 9/14 patients • Number of arteries with FDG uptake grade ≥ 2, median 2 (range 1–5) |
| Castellani et al. (2016) |
TOTAL (N = 21) GCA (n = 16) TAK (n = 5) Refractory Remission Relapse |
Unclear | Assessment of clinical course (clinical and laboratory data, response to GC treatment); no standardized criteria | GC treatment or immunosuppressants |
Diagnostic accuracy of scan for assessment of disease activity (n = 41 scans; clinically active disease during 15 scans; clinical remission during 26 scans): • Visual grading: supra-aortic branches AUC 0.687, Sens 73%, Spec 54%; thoracic aorta AUC 0.744, Sens 67%, Spec 73%; abdominal aorta AUC 0.692, Sens 80%, Spec 68%; iliofemoral arteries AUC 0.686, Sens 33%, Spec 96%; total visual score of 11 regions in aortic tree AUC 0.736, Sens 73%, Spec 81% • TBR (SUVmean artery/SUVmean liver): supra-aortic branches AUC 0.810, Sens 93%, Spec 58%; thoracic aorta AUC 0.777, Sens 80%, Spec 65%; abdominal aorta AUC 0.738, Sens 93%, Spec 58%; iliofemoral arteries AUC 0.821, Sens 87%, Spec 81%; in entire aortic tree AUC 0.827, Sens 93%, Spec 62% |
| Grayson et al. (2018)b |
TOTAL (n = 56) GCA (n = 30) TAK (n = 26) Newly diagnosed Remission Relapse Possibly refractory At least 69/111 (62%) scans during treatment |
Mean 6.9 years (SD 8.9) |
Active disease = presence of clinical feature attributed to vasculitis (fatigue or elevated acute phase reactants alone not sufficient) Remission = absence of clinical feature attributed to vasculitis |
Clinical active disease (40 scans): prednisone used during 24/40 scans; immune medication used during 27/40 scans Clinical remission (71 scans); prednisone used during 42/71 scans; immune medication used during 42/71 scans |
Scan during clinically active disease (n = 40 scans): nuclear medicine physician global impression of scan consistent with vasculitis in 34/40 scans Scan during clinical remission (n = 71 scans): nuclear medicine physician global impression of scan consistent with vasculitis in 41/71 scans Diagnostic accuracy of scan for assessment of disease activity: • Nuclear medicine physician global impression, Sens 85%, Spec 42% • PETVAS, AUC 0.72, OPC 20, Sens 68%, Spec 71% |
| Incerti et al. (2017) |
TAK (n = 30) Remission Relapse Possibly refractory |
Median 5 years (range 0–17) | NIH criteria | Any immunosuppressive treatment (n = 27): GC treatment (n = 24) with median dose 5 mg (range 4–50 mg), MTX (n = 13), AZA(n = 6), MMF (n = 1), LEFL (n = 1), sirolimus (n = 1), sulfasalazine (n = 1), IFX (n = 5), adalimumab (n = 2), TCZ (n = 2), golimumab (n = 1) |
Scan during clinically active disease (n = 18) • Vascular FDG uptake grade 1 (= FDG uptake equal to/higher than liver) in 9/18 patients, and in 6/18 patients if FDG uptake at vascular graft is excluded • Number of lesions with significant FDG uptake grade 1, median 0 (0–8), and median 0 (range 0–8) if FDG uptake at vascular graft is excluded • SUVmax, median 1.4 (range 0.1–6.7), and median 0.1 (range 0.1–6.2) if FDG uptake at vascular graft is excluded Scan during clinical remission (n = 12) • Vascular FDG uptake grade 1 in 7/12 patients, and in 7/12 patients if FDG uptake at vascular graft is excluded • Number of lesions with significant FDG uptake grade 1, median 1 (range 0–8), and median 1 (range 0–6) if FDG uptake at vascular graft is excluded • SUVmax, median 2.8 (range 0.1–9.8), and median 2.8 (range 0.1–9.8) if FDG uptake at vascular graft is excluded NB 7/30 patients received a total of 11 arterial grafts; FDG-PET/CT performed after median 37 months (range 12–55 months) after surgery showed vascular FDG uptake grade 1 at 10/11 arterial grafts. SUVmax at grafts, median 3.9 (range 0.1–6.7). |
| Li et al. (2019) |
TAK (n = 22) Remission Relapse At least 69/71 (97%) patients on treatment§ |
Mean 5.4 years (SD 5.5)§ | ITAS2010 |
Treatment of all patients in the study (n = 71) including all patients that underwent FDG-PET/CT (n = 22): Prednisone 69/71 patients, CYC 25/71 patients, LEFL13/71 patients, MMF 11/71 patients, MTX 18/71 patients, TCZ 11/71 patients, tacrolimus 2/71 patients, cyclosporine 2/71 patients§ |
Scan during clinically active disease (n = 12): Vascular FDG uptake grade ≥ 2† in the carotid artery of 9/12 patients Scan during clinical remission (n = 10): vascular FDG uptake grade ≥ 2 in the carotid artery of 2/10 patients |
| Rimland et al. (2020)b |
TOTAL (n = 112) GCA (n = 56) TAK (n = 56) Newly diagnosed Remission Relapse Possibly refractory At least 61/112 (54%) patients on treatment |
Median 2.4 years (IQR 0.7–8.3) | Physician global assessment on a scale of 0 (remission) to 10 (very active diseases) |
Treatment (n = 112) • Prednisone, median dose 5 mg (IQR 0–19.4) • Other immunosuppressant 61/112 patients |
Scan during clinically active disease (n = 82 scans): PETVAS, median 21.5 (IQR 16.8–25.0) (n = 82 scans) Scan during clinical remission (n = 158 scans): PETVAS, median 17.0 (IQR 11.0–21.0) (158 scans) |
| Santhosh et al. (2014) |
TAK (n = 38) Relapse Remission |
Mean 2.9 years (SD 0.6) | National Institute of Health criteria and/or positive FDG-PET/CT | ‘Immunosuppression’ |
Scan during clinically active disease (n = 12 scans) • Pathologic vascular FDG uptake (i.e. grade 3 at ascending aorta, grade ≥ 2 at the aortic arch or large aortic branch, or grade ≥ 1 at descending or abdominal aorta†) in 10 scans Scan during clinical remission (n = 31 scans) • Pathologic vascular FDG uptake (i.e. grade 3 at ascending aorta, grade ≥ 2 at the aortic arch or large aortic branch, or grade ≥ 1 at descending or abdominal aorta†) in 3 scans Diagnostic accuracy of scan for assessment of disease activity: • Sens 83% and Spec 90% |
| Schramm et al. (2019)c,d |
TOTAL (n = 62) GCA (n =?) TAK (n =?) Newly diagnosed Remission Relapse Possibly refractory At least 74/80 (93%) scans on treatment |
Mean 2.0 years (SD 3.3; range 0–15.1) | Physician global assessment based on clinical symptoms and acute phase reactants |
• Prednisolone used during 74/80 scans, mean dose 54 mg (SD 113) • Conventional immunosuppressive treatment during 20/80 scans • Biological immunosuppressive treatment during 8/80 scans |
Scan during clinically active disease: • TBR (SUVmax aorta/SUVmean liver), mean 1.74 (SD 0.60)a • TBR (SUVmax aorta/SUVmean inferior vena cava), mean 2.76 (SD 1.00)b • TBR (SUVmax aorta/SUVmean superior vena cava), mean 2.66 (SD 1.07)b • TBR (SUVmax aorta/SUVmean right atrium), mean 1.81 (SD 0.4)b Scan during clinical remission: • TBR (SUVmax aorta/SUVmean liver), mean 1.18 (SD 1.26)a • TBR (SUVmax aorta/SUVmean inferior vena cava), mean 1.84 (SD 0.27)b • TBR (SUVmax aorta/SUVmean superior vena cava), mean 1.68 (SD 0.31)b • TBR (SUVmax aorta/SUVmean right atrium), mean 1.79 (SD 0.35)b Diagnostic accuracy of scan for assessment of disease activity: • TBR (SUVmax aorta/SUVmean liver), AUC 0.90, Sens 84%, Spec 83%a • TBR (SUVmax aorta/SUVmean inferior vena cava), AUC 0.84, Sens 75%, Spec 100%b • TBR (SUVmax aorta/SUVmean superior vena cava), AUC 0.88, Sens 92%, Spec 75%b • TBR (SUVmax aorta/SUVmean right atrium), AUC 0.52, Sens 75%, Spec 50%b aIncluding 28 FDG-PET/CT scans and 52 FDG-PET scans without CT; active disease during 57/80 scans; bincluding 28 FDG-PET/CT scans; number of scans with active/inactive disease during scan unclear |
| Tezuka et al. (2012)d |
TAK (n = 29) Relapse Remission (‘stable’) |
Unclear | National Institute of Health Criteria | Prednisolone dose, median 10 mg (IQR 6–16) in relapsing patients (n = 17) and 8 mg (IQR 2–15) in patients in remission (n = 12), and additional immunosuppressant in 5 relapsing patients and 3 patients in remission; i.e. CYC (n = 1), cyclosporin (n = 3), MTX (n = 2) or AZA (n = 2) |
Scan during clinically active disease (n = 17): SUVmax, median 2.6 Scan during clinical remission (n = 12): SUVmax, median 1.9 Diagnostic accuracy of scan for assessment of disease activity: • SUVmax, AUC 94% • TBR (SUVmax artery/SUVmean inferior vena cava), AUC 92% |
| Quinn et al. (2018)b |
TOTAL (n = 65) GCA (n = 35) TAK (n = 30) Newly diagnosed Remission Relapse Possibly refractory At least 68/114 (60%) scans during treatment |
Median 2.2 years (IQR 0.9–5.2) in patients with scan during active disease, and median 2.8 years (IQR 1.4–7.3) in patients with scan during remission. |
Active disease = presence of clinical feature attributed to vasculitis (fatigue or elevated acute phase reactants alone not sufficient) Remission = absence of clinical feature attributed to vasculitis (regardless of acute-phase reactants) |
Clinical active disease (n = 45 scans): • Prednisone, median dose 5 mg (IQR 0–30) • Immune medications used during 28/45 scans Clinical remission (n = 69 scans): • Prednisone, median dose 5 mg (IQR 0–10) • Immune medications used during 40/69 scans |
Scan during clinically active disease (n = 45 scans) • Vascular FDG uptake higher than liver in 37/45 scans • PETVAS, median 20.5 (IQR 14–25) Scan during clinical remission (n = 69 scans) • Vascular FDG uptake higher than liver in 43/69 scans • PETVAS, median 18 (IQR 14–25) |
Glucocorticoid treatment was used orally unless stated otherwise. AZA, azathioprine; CYC, cyclophosphamide; GC, glucocorticoid; GCA, giant cell arteritis; IFX, infliximab; ITAS2010, Indian Takayasu’s Arteritis Activity Score 2010; IQR, interquartile range; IV, intravenous; LEFL, leflunomide; MMF, mycophenolate (mofetil); MTX, methotrexate; n, number of patients (unless stated otherwise); NIH, National Institute of Health; SD, standard deviation; TAK, Takayasu arteritis; TBR, target to background ratio; TCZ, tocilizumab
†Vascular FDG uptake grading system: 0 = no uptake, 1 = less than liver, 2 = equal to the liver, 3 = more than liver
§Including data obtained from patients without relevant data
aNot included in the meta-analysis: uncertainty about disease activity during scan
bNot included in the meta-analysis: uncertain if at least 90% of patients were on treatment
cNot included in the meta-analysis: part of scans were [18F]FDG-PET without CT
dNot included in the meta-analysis: no data on the number of true positives, false positives, false negatives and true negatives