Avoidance of Harm From Treatment for ANCA-Associated Vasculitis

Abstract

Opinion statement Purpose of review With established immunosuppressant treatment regimens for anti-neutrophil cytoplasm antibody-associated vasculitides (AAV), prognosis has significantly improved. The mainstay of treatment still comprises high-dose corticosteroids and cyclophosphamide for severe forms, although rituximab is being increasingly utilised instead of cyclophosphamide as induction therapy. AAV patients experience an excess of infections, malignancies and cardiovascular events as compared to the general population, which is a combination of the systemic inflammatory process associated with vasculitis and the adverse events from treatment. Recent findings Successful therapy should focus on suppressing disease activity and minimising treatment-related toxicity. Infection is the largest contributor to morbidity and mortality in the first year of treatment, and annual pneumococcal and influenza vaccinations, Pneumocystis jiroveci prophylaxis and tuberculosis (TB) and Hepatitis B virus screening are advised. Patients on high-dose corticosteroid treatment should have regular blood sugar monitoring, a FRAX assessment with vitamin D and calcium supplementation, consideration of prophylaxis for gastric ulcers and a cardiovascular risk assessment. Patients who are treated with cyclophosphamide could also receive MESNA to reduce the risk of chemical cystitis. Cyclophosphamide, methotrexate and azathioprine all require blood monitoring schedules due to the risk of bone marrow suppression, liver and renal toxicity. Hypogammaglobulinaemia is a recognised risk of rituximab treatment. Patients of reproductive age need to be counselled on the infertility risks with cyclophosphamide and the teratogenicity associated with it, methotrexate and mycophenolate mofetil. Summary A greater focus on identifying clinical and biological markers that will help identify those patients at greatest risk of relapse, e.g. GPA and PR3-ANCA specificity, from those patients at greatest risk of toxicity, e.g. increasing age and declining GFR, is required to allow treatment to be tailored accordingly.

Treatment of Rare Inflammatory Kidney Diseases: Drugs Targeting the Terminal Complement Pathway

“…Though dampening immune system-related symptoms, corticosteroids bear considerable treatment-related morbidities. The consequences are adverse events (AEs) that increase with treatment of longer duration, including risk of infection, weight gain, new onset of diabetes, hypertension, and/or osteoporosis ( 12 , 110 ). In the STOP-IgAN trial, safety and efficacy in IgAN patients on corticosteroids (and nonspecific immunosuppressive agents) compared to supportive care were assessed for 3 years.…”

“…Especially the anaphylatoxin C5a has been associated with inflammatory disorders ( 8 , 9 ), in which the kidney is particularly vulnerable ( 10 ). For many years, treatment of rare inflammatory kidney diseases consisted of supportive measures, such as plasma exchange ( 11 ), or strong nonspecific immunosuppression, including corticosteroids, which is limited by underlying toxicity and adverse events ( 12 ), and many patients progressed to end-stage renal disease (ESRD) requiring dialysis a few years after diagnosis ( 13 , 14 ).…”

Targeting IgG Autoantibodies for Improved Cytotoxicity of Bactericidal Permeability Increasing Protein in Cystic Fibrosis

“…Indeed, a number of biologics targeting immune cells or their secreted components continue to be trialed in such conditions with some success ( Basu et al., 2018 ). However, these ANCA-associated conditions do not co-present with chronic infection, and immunosuppressive therapy in chronically infected PWCF may not be advisable ( King and Harper, 2017 ). Therefore, a targeted approach to abate BPI-ANCA development or function in CF would promote the endogenous antimicrobial BPI activity without off-target effects against the immune system.…”

Rituximab in relapsing and de novo MPO ANCA-associated vasculitis with severe renal involvement: a case series

“…Taking into considerations all these factors the importance of the assessment of the clinical risk factors and BVAS score before the induction treatment should be pointed out, in order to perform an individualized evaluation of the risk of infection. In this setting a particular attention should be paid to the development of Pneumocystis jiroveci pneumonia; some data suggest the prophylaxis with cotrimoxazole in all patients undergoing CYC or RTX treatment [24]. This study is limited by its retrospective design and by the small number of cases and short follow up, nevertheless it focuses on a homogeneous subgroup of patients all affected by MPO-AAV and severe renal involvement.…”