Predictors of Cyclophosphamide Resistance in Granulomatosis with Polyangiitis: A Retrospective Cohort Study

Cyclophosphamide remains a cornerstone of remission induction therapy in granulomatosis with polyangiitis (GPA); however, the presence of resistant patients necessitating a switch to alternative agents, such as rituximab, remains a clinical challenge. Identifying predictors of cyclophosphamide resistance could improve patient stratification and optimise treatment strategies.

This retrospective cohort study included 75 patients diagnosed with GPA and treated at Ankara Bilkent City Hospital between 2018 and 2023.Clinical and laboratory data were extracted from electronic medical records. Baseline characteristics, organ involvement, and serological profiles were compared between cyclophosphamide-responsive and cyclophosphamide-resistant patients. Logistic regression analysis was performed to identify independent predictors of treatment resistance.

75 patients with GPA analysed. The mean age was 46.1years (SD=14.0).56 patients received cyclophosphamide as first-line therapy, of whom 34 (60.7%) achieved remission, while 22 (39.3%) switched to rituximab. Of these, 17 patients (30.4%) were classified as cyclophosphamide-resistant, while 5 patients (8.9%) switched due to other reasons. Younger age was a significant predictor of cyclophosphamide resistance (OR=0.915, 95%CI:0.856-0.977, p=0.008). The presence of arthritis showed a trend toward association (OR=5.191, 95%CI:0.960-28.065, p=0.056) but did not reach statistical significance. No significant differences were observed in gender, ANCA subtypes, major organ involvement, or comorbidity burden between groups.

Our findings suggest that younger age is associated with a higher likelihood of cyclophosphamide resistance in GPA, potentially indicating a more aggressive disease course. Although arthritis showed a potential association with resistance, further studies are needed to confirm its role.