Long-Term Prognostic Factors in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A 15-Year Multicenter Retrospective Study

Abstract

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients.

Materials and methods: A multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results.

Results: In the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676-0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model.

Conclusion: Laboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients.

Keywords: 5-year survival rate; ANCA-associated vasculitis (AAV); decision curve analysis (DCA); nomogram; overall survival (OS); prognosis.

Figure 1

Association of clinical characteristics with overall survival in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. (A) Age. (B) Gender. (C) BVAS, Birmingham vasculitis activity score. (D) Pathological categories (MPA, GPA, and other types). MPA, microscopic polyangiitis; GPA, granulomatosis with polyangiitis. (E) Serum ANCA types (MPO, PR3, negative, and double positive for MPO and PR3) classified by the ELISA. MPO, myeloperoxidase; PR3, proteinase 3. (F) Serum ANCA types (p-ANCA, c-ANCA, negative, and double positive for p-ANCA and c-ANCA) classified by the indirect immunofluorescence (IIF) assay. p-ANCA, perinuclear ANCA; c-ANCA, cytoplasmic ANCA. (G) Negative vs. positive for MPO and/or PR3. (H) Negative vs. positive for p-ANCA and/or c-ANCA. (I) ASO, anti-streptolysin O. (J) ANA, antinuclear antibody. (K) GFR, glomerular filtration rate. (L) ESR, erythrocyte sedimentation rate.

Figure 2

Relationships between hematological parameters and overall survival in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. (A) NLR, neutrophil-to-lymphocyte ratio. (B) RBC, red blood cell. (C) Hb, hemoglobin. (D) Lymphocyte. (E) Eosinophil. (F) TP, total protein. (G) Albumin. (H) A/G, albumin-to-globulin ratio. (I) UA, uric acid. (J) CRP, C-reactive protein. (K) C3, complement 3. (L) Scr, serum creatinine.

Figure 3

Receiver operating characteristic (ROC) curves for the predictive ability of clinical parameters with continuous variables in AAV patients. (A) 3-year survival rate. (B) 5-year survival rate. AAV, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis; BVAS, Birmingham vasculitis activity score; Scr, serum creatinine; GFR, glomerular filtration rate; NLR, neutrophil-to-lymphocyte ratio; RBC, red blood cell; Hb, hemoglobin; TP, total protein; A/G, albumin-to-globulin ratio; UA, uric acid; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; C3, complement 3.

Figure 4

The nomogram for 3-year and 5-year survival rates in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. NLR, neutrophil-to-lymphocyte ratio; GFR, glomerular filtration rate; CRP, C-reactive protein; ASO, anti-streptolysin O; ANA, antinuclear antibody; ANCA ELISA only, serum ANCA types (negative or positive for MPO and/or PR3) only classified using ELISA. MPO, myeloperoxidase; PR3, proteinase 3; UK, unknown, meaning that a clinical parameter was assigned to a score corresponding to “UK” when the clinical parameter was not detected.

Figure 5

The calibration curves and decision curve analysis (DAC) of the nomogram in AAV. (A) The nomogram calibration curve for the 3-year survival rate in AAV patients. (B) The nomogram calibration curve for the 5-year survival rate in AAV patients. (C) Nomogram decision curve analysis (DCA) for the 3-year survival rate in AAV patients. (D) Nomogram DCA for the 5-year survival rate in AAV patients. AAV, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. In panels (A, B), the dashed lines serve as the reference lines. In panels (C, D), the horizontal black line and green oblique line refer to no AAV patient and all AAV patients, respectively.