Risk Relapse Score for ANCA-Associated Vasculitis Treated With CYC

Although cyclophosphamide (CYC) is a cornerstone of induction therapy in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), the risk factors for relapse in patients undergoing CYC therapy are not well understood. Gianmarco Lugli and a team of researchers set out to develop a clinically useful tool to score robust predictors of relapse in these patients. Their results were presented at the 61st European Renal Association Congress.

Study participants came from Ireland, Italy, and Spain; were aged >18 years; had a diagnosis of granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or eosinophilic granulomatosis with polyangiitis (EGPA); underwent induction treatment with intravenous (IV) or oral CYC; and had at least 12 months of follow-up.

The research team used a multivariate Cox analysis to develop the Relapse Evaluation and Cyclophosphamide Treatment (REACT) score, assigning each predictor a certain number of weighted points in proportion to its β regression coefficient.

The baseline assessment included clinical data, lab testing, and measurement of signs of GPA, MPA, and EGPA in each organ system. Relapse was defined as the presence of one or more new vasculitis manifestation after a remission of at least 3 months. Remission was defined as no disease activity regardless of glucocorticoid use. The Kaplan-Meier method was used to estimate time-to-remission and relapse-free survival probabilities.

There were 505 patients in the cohort; 223 (44.2%) had MPA, 217 (43.0%) had GPA, and 65 (12.9%) had EGPA. Of the total cohort, 183 (36.2%) patients experienced an AAV relapse. Multivariate Cox analysis found that independent risk factors for relapse included proteinase 3-ANCA (hazard ratio [HR], 1.30; 95% CI, 1.01-1.87), IV CYC (HR, 1.78; 95% CI, 1.31-2.41), cardiovascular (CV) involvement (HR, 1.82; 95% CI, 1.01-3.25), arthralgias/arthritis (HR, 1.46; 95% CI, 1.08-1.98), and the absence of rapidly progressive glomerulonephritis (HR, 1.37; 95% CI, 1.02-1.85).

For the creation of the REACT score, CV involvement and IV CYC each received two points, but otherwise each variable was assigned one point. Researchers identified three risk categories according to each patient’s score: low risk of relapse (score zero or one), which comprised 138 (27%) patients; intermediate risk (score two or three), with 252 (49%) patients; and high risk (score four to seven), which included 115 (22%) patients. Kaplan-Meier analysis with paired comparisons between the risk groups found statistically significant differences in relapse probabilities among them.

The study authors concluded, “The REACT score can be employed at diagnosis to predict the risk of relapse in patients with AAV treated with [CYC] induction. Its value needs to be confirmed in external cohorts.”

Source: Lugli G, Buscemi P, Calatroni M, et al. Development of a relapse risk score in patients with ANCA-associated vasculitis treated with cyclophosphamide induction. Abstract #1484. Presented at the 61st European Renal Association Congress; May 23-26, 2024; Stockholm, Sweden.