#4732 GLUCOCORTICOID-RELATED ADVERSE EFFECTS IN THE TREATMENT OF ANCA-ASSOCIATED VASCULITIS
Authors: Plappert David , Ketteler Markus , Schanz Moritz , Schmid Nico 
Published: June 2023

Abstract

Background and Aims
Upcoming glucocorticoid (GC)-sparing treatment strategies like avacopan could potentially diminish or replace the need of GC therapy for ANCA-associated-vasculitis (AAV) in the future. Therefore, a proper assessment of GC-related morbidity in AAV is required to provide further justification of such therapies. The aim of this study was therefore to assess the incidence of common toxicities and to further investigate the effect of GC-treatment on the incidence and management of diabetes mellitus, arterial hypertension and hypercholesterolemia.

Method
In this single-centre-cohort-study we screened medical records for patients with a diagnosis of AAV admitted to the Robert-Bosch-hospital (RBK) in Stuttgart, Germany on a regular basis. We assessed the dosage and duration of immunosuppressive therapy used to treat AAV, as well as the incidence and therapies of arterial hypertension, diabetes mellitus and hypercholesterolemia. For this study, we observed the vasculitis time course during the acute phase (180 days) after either the initial diagnosis or relapse for each patient.

Results
We included 74 patients admitted to the RBK since 2004 up to the current date. Most common subtype of AAV was GPA (n = 48 patients), followed by MPA (n = 22) and EGPA (n = 4). Including relapses, a total of 127 events were observed. We followed patients for a mean time of 8 years (SD 3.9, 0.9 - 18.0 years). Mean duration of glucocorticoid therapy in total was 4.2 years (SD 3.6, 0.3-14.7 years). All of the patients received prednisolone, whereas 73% of the patients furthermore were administered methylprednisolone for induction therapy. Overall, 34% of the patients were diagnosed with diabetes before or after the diagnosis of AAV (14% pre-existing diabetes, 20% new-onset diabetes). Daily and accumulated GC-dose did not differ between patients with or without diabetes. However, there was a significant higher accumulated GC dose in patients requiring insulin-therapy for diabetes management in comparison to those with oral antidiabetics (p-value = 0.0214). 89% of the patients were treated with antihypertensive therapy (38% pre-exisiting hypertension, 51% new-onset hypertension). We found that the accumulated dose of prednisolone within the first 180 days after a vasculitis event was not significantly higher for patients with documented hypertension. However, we detected that the mean accumulated GC dose after a vasculitis event was significantly higher for the subgroup of patients in whom an escalation of antihypertensive therapy was initiated in comparison to the patients whose therapy was stable or even deescalated (p-value = 0.0001). With regard to hypercholesterolaemia, there was no statistical difference in the accumulated GC-dose during the acute course between patients requiring statin-therapy and those who did not.

Conclusion
GC related toxicities are common in patients with AAV. This study provides additional evidence about the incidence of treatment related harms in AAV to further promote importance of alternative reduced dose or even GC free treatment approaches. This may be relevant in detecting risk groups for whom upcoming GC-sparing treatment strategies such as avacopan are essential to reduce treatment-related harm.