Background/Purpose: Failure of a first-line anti-TNF in axial spondyloarthritis (axSpA) is common, and when it occurs, there are no randomized clinical trials (RCTs) comparing the option of switching to a drug with a different mechanism of action (MoA) or cycling to a different anti-TNF. The aim of this study is to evaluate whether these treatment strategies influence the retention to second-line therapy after failure of first-line anti-TNF.

Methods: Data were obtained from the nationwide prospective registry BIOBADASER (Spanish Registry of Adverse Events of Targeted Therapies in Rheumatic Diseases). Patients diagnosed with axSpA who had failed a first TNFi and were starting a second advanced treatment (anti-TNF, IL17 inhibitors or JAK inhibitors) after 2016 were included in the study. Demographic variables, presence of HLA-B27, axSpA manifestations, as well as start and end dates of treatment and reasons for discontinuation were included in the study. Retention rates of the different drugs were estimated using Kaplan-Meier curves and Log rank test, considering discontinuation due to inefficacy or loss of efficacy as a completion event. Predictors of discontinuation were examined using the Cox multivariate regression model.

Results: A total of 827 axSpA patients who met inclusion criteria were included in the analysis, 603 (72.9%) continued to another TNFi and 224 (27.1%) switched to different MoA (90.6% to an IL-17 inhibitor). Of all patients, 306 (37.0%) were female, mean (SD) age at treatment initiation was 48.4 (13.0) years, 697 (84.3%) had radiographic axSpA and 547 (66.1%) were HLA-B27 positive, with a mean disease duration of 9.8 (9.8) years. No statistically significant differences in baseline characteristics were found between the two groups, except for a higher percentage of patients initiating second-line treatment after 2020 in the switch cohort versus the cycling cohort (60.3% vs 45.4%; p < 0.001).The one-year retention rate until inefficacy was significantly higher in the cycling cohort compared to the switching cohort (82.3%; 95%CI [78.8 - 85.4] vs 71.3% [64.5 - 77.1]; Log Rank < 0,01) (Figure 1).In the univariate analysis, switching to a different MoA was associated with a higher probability of treatment discontinuation (HR: 1.49 [1.14 - 1.90]; p = 0.004) (Table 1). This finding was confirmed in the multivariate analysis (HR: 1.50 [1.14–1.98]; p = 0.004). Other significant predictors of increased risk of discontinuation were obesity (HR: 1.57 [1.11–2.23]; p = 0.011) and nr-axSpA diagnosis (HR: 1.74 [1.23 - 2.44]; p = 0,002). In contrast, HLA-B27 positivity (HR: 0.70 [0.52–0.94]; p = 0.017) and second-line treatment initiation after 2020 (HR: 0.61 [0.46 - 0.80]; p < 0,001) were associated with a lower probability of discontinuation, suggesting a protective effect (Table 1).

Conclusion: In patients with axSpA, cycling to another anti-TNF agent after first-line anti-TNF failure is associated with a lower risk of discontinuation compared to switching to a treatment with a different mechanism of action.HLA-B27 positivity and treatment initiation after 2020 were also associated with a lower risk of discontinuation. In contrast, obesity and nr-axSpA diagnosis were associated with higher risk of discontinuation.

Figure 1. Kaplan – Meier survival estimates

Table 1. Univariate and Multivariate models.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/persistence-of-second-line-treatment-in-anti-tnf-experienced-axial-spondyloarthritis-patients-comparing-cycling-anti-tnf-vs-switching-to-a-different-mechanism-of-action/