CLINICAL IMPACT OF IMMUNOSUPPRESSIVE COMBINATION THERAPY IN MPO-ANCA–ASSOCIATED RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS: A RETROSPECTIVE COMPARISON WITH STEROID MONOTHERAPY

Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) predominantly affects elderly individuals and often presents with rapidly progressive glomerulonephritis (RPGN). The standard treatment consists of corticosteroids combined with immunosuppressive agents. However, in elderly patients, adverse events such as severe infections are major concerns, and tailoring treatment intensity is essential.
At our institution, corticosteroid monotherapy or immunosuppressive combination therapy has been selected according to disease activity and comorbidities. This study aimed to compare the clinical course, renal outcomes, and safety between the two treatment strategies in MPO-ANCA–associated RPGN.

We retrospectively analyzed patients diagnosed with AAV-related RPGN at our hospital between April 2012 and March 2025.
Inclusion criteria:
(1) Age ≥18 years;
(2) positive for myeloperoxidase (MPO)-ANCA;
(3) diagnosis of microscopic polyangiitis (MPA); and
(4) ≥6 months of follow-up after initiation of therapy.

Exclusion criteria:
(1) proteinase-3 (PR3)-ANCA positivity,
(2) anti-glomerular basement membrane (GBM) antibody positivity,
(3) drug-induced vasculitis, and
(4) patients who required maintenance dialysis from the time of diagnosis.

A total of 70 patients were included: 44 in the steroid monotherapy group and 26 in the immunosuppressive combination group.
Immunosuppressive agents included rituximab (RTX), azathioprine (AZA), and avacopan, and treatment choice was at the discretion of the attending physician.

Clinical characteristics, urinary findings, and laboratory parameters (CRP, eGFR, MPO-ANCA) were compared at baseline and at 2 weeks, 4 weeks, 3 months, 6 months, and 12 months after treatment initiation.
Outcomes at 12 months included remission rate, mortality, severe infection, transition to maintenance dialysis, new-onset diabetes mellitus, and relapse within 12 months.

Definitions:
Remission was defined as complete disappearance of clinical disease activity with a Birmingham Vasculitis Activity Score (BVAS, version 3; range 0–63, higher scores indicating greater activity) of 0, and stable prednisone ≤7.5 mg/day according to the EULAR recommendations.
Severe infection was defined as an infection that was fatal, required hospitalization, or required intravenous antibiotic therapy.
Relapse was defined as any episode during treatment that required intensification of immunosuppressive therapy.

Statistical analyses were performed using R version 4.4.2.
Continuous variables were analyzed using the Mann–Whitney U test, and categorical variables using the chi-square or Fisher’s exact test. A two-sided p < 0.05 was considered statistically significant.

1. Baseline characteristics

Median age was 77 years [IQR 72–82] in the monotherapy group and 78 years [IQR 73–81] in the combination group, with no significant difference (p = 0.584).
No differences were observed in BVAS, eGFR, CRP, or urinary protein levels, indicating comparable disease activity and renal impairment.
The renal biopsy rate was higher in the monotherapy group (65.9% vs. 38.5%, p = 0.047), suggesting more clinically diagnosed cases in the combination group.
Initial oral steroid dose and pulse therapy frequency were similar between groups.

2. Immunosuppressive usage

In the combination group, rituximab (65.4%), azathioprine (30.8%), and avacopan (19.2%) were used significantly more often than in the monotherapy group (p < 0.001, p = 0.011).

3. Laboratory course

Over 12 months, improvements in CRP, eGFR, and MPO-ANCA titers were comparable between the groups, with no significant inter-group differences at any time point.
Changes in eGFR from baseline (ΔeGFR) were also similar, indicating parallel renal recovery and stabilization.

4. Steroid exposure and remission

The total corticosteroid dose at 12 months was significantly lower in the combination group (5827 mg vs. 5414 mg, p = 0.013), demonstrating that concomitant immunosuppressive therapy allowed meaningful steroid reduction without loss of efficacy.
The median time to remission was 5 months in both groups (no significant difference).
Remission, as defined by BVAS = 0 and prednisone ≤7.5 mg/day, was achieved in the majority of patients in both groups.

5. Outcomes at 12 months

Mortality at 12 months was 0% in the monotherapy group and 3.8% in the combination group (p = 0.789).
Severe infections occurred more frequently in the combination group (19.2% vs. 6.8%, p = 0.235), though not statistically significant.
Relapse within 12 months occurred infrequently and did not differ between groups.
Remission rates were high and comparable (88.6% vs. 92.3%, p = 0.642).
There were no significant differences in progression to maintenance dialysis or new-onset diabetes mellitus between groups.

In elderly patients with MPO-ANCA–associated RPGN, immunosuppressive combination therapy achieved clinical outcomes comparable to corticosteroid monotherapy while allowing a significant reduction in cumulative steroid dose.
Based on standardized definitions, remission (BVAS = 0 and prednisone ≤7.5 mg/day) was achieved in both groups with similar relapse rates during the 12-month follow-up.
Although the incidence of severe infections tended to be higher in the combination group, overall safety remained acceptable.
These findings suggest that combination therapy—including rituximab and avacopan—offers a valuable, steroid-sparing treatment option for elderly AAV patients, enabling durable remission without compromising safety.
Further multicenter studies are warranted to establish optimal immunosuppressive strategies and identify predictors of relapse in this population.