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 $$\ge $$ ≥ 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 $$\ge $$ ≥ 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.

No 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 ± SD 29 ± 20 mL/min/1.73 m 2 vs 35 ± 26 mL/min/1.73 m 2 , P = .34) and improved after 2 years irrespective of the cyclophosphamide dose (DeGFR, mean ± SD +8.9 ± 1.4 mL/min/1.73 m 2 vs +6.0 ± 1.1 mL/min/1.73 m 2 , P = .33). The 2.5-3 g group had a lower rate of leukopenia (HR = 2.73 [95% CI, 1.2À6.3], 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.Abbreviations: AAV = ANCA-associated vasculitis, CYC = cyclophosphamide, ESKD = end-stage kidney disease, GPA = granulomatosis with polyangiitis, HR = hazard ratio, IV = intravenous, MPO = myeloperoxidase, PR3 = proteinase 3, RTX = rituximab.

BackgroundC-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are important parameters in the monitoring of LVV. Since Tocilizumab is approved for treatment of LVV these cheap and easy repeatable parameters are worthless because of their normalisation by Tocilizumab. MRI and PET-CT as an alternative are not only much more expensive, they are also not arbitrarily repeatable and available. Thus, monitoring of LVV-Patients undergoing a Tocilizumab therapy remains unclear – especially upon showing a persisting thickened vessel wall.ObjectivesCEUS can increase the visibility of tissue perfusion, particularly if there is a very slow bloodflow, which cannot be detected by (power)-doppler sonography.MethodsIn this proof of concept study we investigated patients with active and inactive LVV (aLVV/iLVV) with CEUS. After injection of ultrasound contrast agent we measured the contrasted area of large vessels in a transverse section first if the lumen was completely contrasted and once again 4-8 seconds later. If the vessel wall incorporated the contrast agent the contrasted area increased (Fig 1). The increase of the contrasted area (CA) was correlated with CRP and ESR. Patients were only included if they were not treated with Tocilizumab and therefore ESR and CRP were usable to evaluate the disease activity.ResultsInvestigated were 16 patients (13 female, 3 male), 8 with aLVV and 8 with iLVV, respectively. The mean CRP was 85±69 (aLVV) vs. 4±2 mg/l (iLVV) (p<0.0001), the ESR 80±28 (aLVV) vs. 7±4 (iLVV) mm/h (p< 0.0001). The mean age was 74.6±8.4 y (range 56-82). The increase of the CA was 66.6±44.6 (aLVV) vs. 2.4±6.6% (iLVV) (p<0.0001). The increase correlated significantly with the CRP r=0.87, p<0.0001. An increase of CA of ≥20% has a sensitivity of 92,3% and a specificity of 90% for active LVV.ConclusionThe results of our proof of concept study demonstrate, that CEUS can detect aLVV with a good sensitivity and specificity. Including CEUS in clinical routine will be much easier repeatable, save, quicker and by far more cost-effective then MRI or PET-CT. CEUS might be a good method for monitoring disease activity in LVV treated with Tocilizumab. The limitation of our study is the small number of patients, the missing blinding of the investigator and the method intrinsic fact, that you can’t investigate all involved vessels by ultrasound/CEUS.ReferencesNoneFig.1Disclosure of InterestsRaoul Bergner Speakers bureau: Abbvie, Roche, Novartis, Bristol Myers Squibb, Jan Splitthoff: None declared, Daniel Wadsack Speakers bureau: Bristol Myers Squibb