Use of Contrast-Enhanced Ultrasound Sonography in Giant Cell Arteritis: A Proof-of-Concept Study.

C-Reactive protein and erythrocyte sedimentation rate are crucial parameters used to monitor giant cell arteritis (GCA). Given that tocilizumab is approved for the treatment of GCA, these parameters are less sensitive because of the effects of interleukin-6 receptor blockade. Thus, the optimal method for monitoring GCA patients undergoing tocilizumab therapy, especially patients exhibiting a persistent thickened vessel wall in large vessels, remains unclear. Contrast-enhanced ultrasonography (CEUS) can increase the visibility of tissue perfusion by slow blood flow, which cannot be detected by power color doppler. We used CEUS to investigate patients with active and inactive GCA of the large vessels (active large vessel arteritis [aLVV]/inactive large vessel arteritis [iLVV]) who were not administered tocilizumab in this proof-of-concept study. After injection of the ultrasound contrast agent, the contrasted area (CA) of large vessels in a transverse section was calculated twice: first when the lumen was contrasted completely and once again 4-8 s later. We investigated the value of increase in CA that exhibited the best sensitivity and specificity for aLVV. Twenty-four patients were included in this study: 15 with aLVV and 9 with iLVV. The CA increased from 32.2 ± 16.8 to 52.5 ± 21.3 mm2 (p < 0.0001) in aLVV. The mean CA remained unchanged in iLVV. The best cutoff value to differentiate between aLVV and iLVV was a ≥25% increase in CA with a sensitivity and specificity of 91.7% and 100%, respectively. Our study indicates that CEUS can detect aLVV with high sensitivity and specificity. Incorporation of CEUS into routine clinical practice might result in a good method for monitoring disease activity in LVV in GCA patients. The limitation of our study was the small number of patients and the lack of investigator blinding to clinical data.

Cyclophosphamide induction dose and outcomes in ANCA-associated vasculitis with renal involvement: A comparative cohort study.

ABSTRACT: Treatment of ANCA-associated vasculitis (AAV) improved over the last decades but disease-unspecific agents such as cyclophosphamide are still associated with serious adverse events, including high rates of infectious complications and malignancy with increased mortality.In this comparative cohort study, we included 121 AAV patients with renal involvement from 2 German vasculitis centers. Patients were separated into subsequent groups: 2.5 to 3 g vs >3 g cumulative cyclophosphamide induction dose. We investigated if a cyclophosphamide induction dose of 2.5 to 3 g could maintain efficacy while minimizing adverse events in AAV patients with renal involvement.Patients with 2.5 to 3 g vs >3 g cumulative cyclophosphamide (median 3.0 g vs 5.5 g, P < .001) had a comparable time to remission (median 4.0 vs 3.8 months, log-rank P = .87) with 90.6% and 91.5% achieving remission after 12 months. Refractory disease was low in both groups (median 3.6% vs 6.2%, P = .68) and relapse rate did not differ (median 36% vs 42%, log-rank P = .51). Kidney function was comparable at disease onset in both groups (eGFR, mean ±â€ŠSD 29 ±â€Š20 mL/min/1.73 m2 vs 35 ±â€Š26 mL/min/1.73 m2, P = .34) and improved after 2 years irrespective of the cyclophosphamide dose (ΔeGFR, mean ±â€ŠSD +8.9 ±â€Š1.4 mL/min/1.73 m2 vs +6.0 ±â€Š1.1 mL/min/1.73 m2, P = .33). The 2.5-3 g group had a lower rate of leukopenia (HR = 2.73 [95% CI, 1.2-6.3], P = .014) and less infectious episodes per patient (median 1.2 vs 0.7, P = .012), especially urinary tract infections (HR = 2.15 [95% CI, 1.1-4.5], P = .032).A cyclophosphamide induction dose of 2.5 to 3 g was able to induce remission and prevent from relapses with fewer cases of leukopenia and less infectious episodes during follow-up. Especially elderly AAV patients who are particularly susceptible to infectious complications could benefit from minimizing dosing regimens with maintained efficacy to control disease activity.

Glucocorticoid maintenance therapy and severe infectious complications in ANCA-associated vasculitis: a retrospective analysis.

To study the impact of glucocorticoid maintenance dose and treatment duration on outcomes in patients with AAV (ANCA-associated vasculitis) with emphasis on infectious complications. A total of 130 AAV patients from two German vasculitis centers diagnosed between August 2004 and January 2019 treated with cyclophosphamide and glucocorticoids for induction therapy and glucocorticoids for maintenance therapy were retrospectively enrolled. We investigated the influence of glucocorticoid maintenance therapy on patient survival, time to relapse, kidney function, infectious complications and irreversible physical damage. The patients were divided into the following groups: patients treated according to the predefined reduction scheme (< 7.5 mg) or patients treated with glucocorticoids ≥ 7.5 mg after 6 months. Compared to patients receiving < 7.5 mg glucocorticoids after 6 months, patients receiving [Formula: see text] 7.5 mg had an increased rate of infectious episodes per patient (1.7 vs. 0.6; p < 0.001), including urinary tract infection (p = 0.007), pneumonia (p = 0.003), opportunistic pneumonia (p = 0.022) and sepsis (p = 0.008). Especially pneumonia during the first 24 months after disease onset [hazard ratio, 3.0 (95% CI 1.5 - 6.1)] led to more deaths from infection (p = 0.034). Glucocorticoid maintenance therapy after 6 months had no impact on relapse rate or patient survival and decline in kidney function was comparable. Glucocorticoid maintenance therapy with [Formula: see text] 7.5 mg after 6 months is associated with more severe infectious complications leading to an increased frequency of deaths from infection. Glucocorticoid maintenance therapy has no effect on time to relapse or patient survival and should therefore be critically revised throughout the aftercare of AAV patients.