Major Infections Are Main Cause of Death in AAV Patients, Study Finds

Major infections are the main cause of poor long-term outcomes and death in patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, a Spanish study found.

The study, “Prevalence and Risk Factors for Major Infections In Patients with Anca-associated Vasculitis. Influence on The Disease Outcome,” was published in The Journal of Rheumatology.

ANCA-associated vasculitis (AAV) is a systemic disease characterized by inflammation and damage to small blood vessels, triggered by uncontrolled production of ANCA autoantibodies.

Treatment with corticosteroids and cyclophosphamide has significantly improved patient outcomes and survival rates of AAV patients, but at the cost of treatment-related toxicity.

“While in the past patients tended to die early due to uncontrolled disease, nowadays treatment- related toxicity plays a central role in mortality,” researchers said.

Infections have been reported as one of the most important clinical manifestations linked to AAV mortality, cited as the cause of death in up to 66% of AAV cases during the first year after diagnosis.

Thus, Spanish researchers conducted a retrospective study to evaluate the prevalence and risk factors of major infections among patients with AAV, and their influence on disease outcomes.

They reviewed clinical records from 132 AAV patients, followed for a mean period of 12 months at a single clinical site. Overall, 51 patients had microscopic polyangiitis (MPA), 52 granulomatosis with polyangiitis (GPA), and 29 had eosinophilic granulomatosis with polyangiitis (EGPA).

During follow-up, 79 patients experienced 300 major infections, with 32 patients having two or more. The infections occurred mostly in the lower respiratory tract (64%), urinary tract (11%), gastrointestinal tract (8%), soft tissues (6%), and central nervous system (0.3%).

No differences in infection rate were observed between different AAV subtypes.

In most cases, infections were caused by bacteria, and 7.4% of the total infections were considered opportunistic, meaning they occurred when the patient’s immune system was weak.

These opportunistic infections happened mainly in the first year of diagnosis (46%), during treatment with the immunosuppressant cyclophosphamide (55%), or after prior treatment with a high immunosuppressant load (18%).

Overall, 5.3% of patients died in the first year, and 14.4% within the first five years. Disease activity and active infections were among the two major risk factors predicting mortality.

“In our series, mortality was clearly related to the disease activity and to the presence of major infections, and the strong association between both hampered elucidations of which of the two causes was the main factor in some cases,” researchers said.

“Although active disease still remains one of the main causes of death in patients with AAV, especially in the first months of follow-up, infectious events play a key role in the prognosis throughout the disease course,” they added.

In general, mortality rates were higher among patients with MPA than in those with GPA or EGPA. Also, patients who were positive for myeloperoxidase (MPO) antibodies had twice the risk of death compared to those with proteinase 3 (PR3) antibodies or negative for any ANCA antibodies.

The team believes that stratifying treatment according to disease severity and identifying predisposition factors to infections — such as intensive immunosuppressive treatment regimens, severe renal dysfunction, and low white blood cell count — are critical to improve patient outcomes.

Such an approach may help achieve the best balance “between the risk of relapses and/or persistent activity and the risk of unwanted treatment side effects,” they said.