Abatacept as Monotherapy and in Combination With Methotrexate in Patients With Juvenile Idiopathic Arthritis: Analysis of 2 Phase III Trials

Ruperto, Nicolino; Lovell, Daniel J.; Berman, Alberto; Antón, Jordi; Viola, Diego Oscar; Lauwerys, Bernard; Rama, Maria Elena; Bohnsack, John F.; Breedt, Johannes; Fischbach, Michel; Lutz, Thomas; Minden, Kirsten; Ally, Mahmood Moosa Tar Mahomed; Rubio-Pérez, Nadina; Gervais, Elisabeth; Zyl, Riana Van; Wong, Robert; Askelson, Margarita; Martini, Alberto; Brunner, Hermine I.

doi:10.3899/jrheum.2022-1320

Cited by 2 publications

(1 citation statement)

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“…Very high levels of S100A8/9 and S100A12 are reported in patients with systemic JIA, especially those with high disease activity [ 14 , 36 , 37 ]. In our study, S100A8/9 and S100A12 levels generally decreased more in patients with pJIA who responded to therapy by month 4 than those classified as non-responders.…”

Section: Discussionmentioning

confidence: 99%

S100 proteins as potential predictive biomarkers of abatacept response in polyarticular juvenile idiopathic arthritis

Brunner,

Schulert,

Sproles

et al. 2024

Arthritis Res Ther

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Background Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of conditions that can cause marked disability and diminished quality of life. Data on predictors of clinical response are insufficient to guide selection of the appropriate biologic agent for individual patients. This study aimed to investigate the propensity of S100A8/9 and S100A12 as predictive biomarkers of abatacept response in polyarticular-course juvenile idiopathic arthritis (pJIA). Methods Data from a phase 3 trial (NCT01844518) of subcutaneous abatacept in patients with active pJIA (n = 219) were used in this exploratory analysis. Association between biomarker levels at baseline and improvements in JIA-American College of Rheumatology (ACR) criteria responses or baseline disease activity (measured by Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein [JADAS27-CRP]) were assessed. Biomarker level changes from baseline to month 4 were assessed for disease outcome prediction up to 21 months. Results At baseline, 158 patients had available biomarker samples. Lower baseline S100A8/9 levels (≤ 3295 ng/mL) were associated with greater odds of achieving JIA-ACR90 (odds ratio [OR]: 2.54 [95% confidence interval (CI): 1.25–5.18]), JIA-ACR100 (OR: 3.72 [95% CI: 1.48–9.37]), JIA-ACR inactive disease (ID; OR: 4.25 [95% CI: 2.03–8.92]), JADAS27-CRP ID (OR: 2.34 [95% CI: 1.02–5.39]) at month 4, and JIA-ACR ID (OR: 3.01 [95% CI: 1.57–5.78]) at month 16. Lower baseline S100A12 levels (≤ 176 ng/mL) were associated with greater odds of achieving JIA-ACR90 (OR: 2.52 [95% CI: 1.23–5.13]), JIA-ACR100 (OR: 3.68 [95% CI: 1.46–9.28]), JIA-ACR ID (OR: 3.66 [95% CI: 1.76–7.61]), JIA-ACR90 (OR: 2.03 [95% CI: 1.07–3.87]), JIA-ACR100 (OR: 2.14 [95% CI: 1.10–4.17]), and JIA-ACR ID (OR: 4.22 [95% CI: 2.15–8.29]) at month 16. From baseline to month 4, decreases in S100A8/9 and S100A12 generally exceeded 50% among JIA-ACR90/100/ID responders. Conclusion Lower baseline levels of S100A8/9 and S100A12 proteins predicted better response to abatacept treatment than higher levels and may serve as early predictive biomarkers in pJIA. Decreases in these biomarker levels may also predict longer-term response to abatacept in pJIA.

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Section: Discussionmentioning

confidence: 99%