Peripheral blood cell dynamics during biological therapy in axial spondyloarthritis: association between lymphocytosis and treatment response.

OBJECTIVE: To investigate longitudinal changes in absolute lymphocyte counts and derived hematological ratios during biological therapy in axSpA, to evaluate the relationship between lymphocytosis and treatment response, and to compare lymphocytosis rates between TNFi- and IL-17i-treated patients. METHODS: This retrospective cohort study included 125 axSpA patients receiving biological therapy at a tertiary rheumatology center. Absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were evaluated at baseline and at 6, 12, and 24 months. Longitudinal changes were assessed using the Friedman test. Treatment response was defined as BASDAI50 achievement. Lymphocytosis was defined as an absolute lymphocyte count > 3.5 × 10⁹/L. Kaplan-Meier and logistic regression analyses were performed to evaluate time-to-lymphocytosis and identify independent predictors. RESULTS: Absolute lymphocyte counts increased significantly during follow-up (p = 0.001), while platelet counts decreased (p = 0.001) and monocyte counts remained stable (p = 0.232). NLR, PLR, and MLR all decreased significantly (all p = 0.001). Lymphocytosis developed in 34.7% of patients and was significantly associated with BASDAI50 response (89.1% vs. 69.3%, p = 0.014). Lymphocytosis developed significantly less frequently in IL-17i than TNFi-treated patients (11.8% vs. 38.4%, p = 0.004). On multivariable analysis, biological therapy class was independently associated with lymphocytosis development (OR = 0.215, 95% CI 0.069-0.667, p = 0.008). Most lymphocytosis events occurred within the first 2 years of therapy. CONCLUSION: Biological therapy in axSpA is associated with increasing lymphocyte counts and decreasing inflammatory hematologic ratios. Lymphocytosis was associated with BASDAI50 response, suggesting it may represent a hematological correlate of therapeutic efficacy. The significantly lower lymphocytosis rate in IL-17i-treated patients suggests differential class-specific effects on peripheral blood cell homeostasis. Key Points • Biological therapy in axSpA was associated with progressive increases in peripheral lymphocyte counts. • Lymphocytosis is significantly associated with BASDAI50 treatment response in axSpA. • IL-17i-treated patients develop lymphocytosis significantly less frequently than TNFi-treated patients. • Biological therapy class is independently associated with lymphocytosis development.