ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0830

The Upregulation of MAP Kinase Pathway Genes Is Associated with Poor Treatment Response to Tofacitinib in Polyarticular Course Juvenile Idiopathic Arthritis

Esraa Eloseily1, Alex Pickering2, Sanjeev Dhakal1, Hermine Brunner3, Sherry Thornton4 and Alexei Grom1, 1Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2Harvard Medical School Department of Biomedical Informatics, Boston, MA, 3Cincinnati Children's Hospital Medical Center, Division of Rheumatology, Cincinnati, OH, 4Cincinnati Children's Hospital, Cincinnati, OH

Meeting: ACR Convergence 2023

Keywords: , ,

Session Information

Date: Sunday, November 12, 2023

Title: Abstracts: Pediatric Rheumatology – Clinical I: JIA

Session Type: Abstract Session

Session Time: 4:00PM-5:30PM

Background/Purpose: Despite significant progress in understanding the pathophysiology of Juvenile Idiopathic Arthritis (JIA), the availability of tools to accurately predict treatment response remains limited. Our objective was to identify gene expression patterns that may predict treatment response to tofacitnib in patients with polyarticular course JIA.

Methods: Whole blood samples were collected from JIA patients using PAXgene tubes prior to starting tofacitinib treatment as part of the clinical trial NCT02592434. Patients were categorized as treatment responders (TR) if they achieved a JIA-ACR70 response or higher at week 18, while those with a JIA-ACR response of 30 or less were considered poor responders (PR). Bulk RNA sequencing was performed using Illumina Nova-seq, generating 50 million reads per sample. Gene expression levels were measured at baseline. Differential gene expression analyses were conducted using the dream method from variance Partition. Gene ontology overrepresentation analyses were subsequently performed using the dseqr adaptation of the goana function from the limma R package.

Results: 663 of 31,799 genes assayed were identified as differentially expressed in PR as compared to TR (FDR< 0.05) from samples acquired prior to treatment initiation. Gene ontology analysis revealed a significant upregulation of genes associated with MAP kinase pathway activation in PR (p=9.40E-05) (Figure 1.a &1.b). Other ontologies that were upregulated in PR included myeloid stem cell development (p=8.13E-05), activation of GTPase activity (p=0.00015), and organelle transport along microtubule (p= 0.00021) (Table 1).

Conclusion: Assessment of MAP kinase pathway gene expression prior to treatment may aid in identification of polyarticular course JIA patients that could exhibit poor response to tofacitinib. If confirmed, this finding could be used to personalize treatment of JIA patients for whom tofacitinib treatment is considered.

Supporting image 1

Figure 1.a: Expression of MAPK genes at baseline in treatment responders versus poor responders after covariate modeling

Supporting image 2

Figure 1.b: Visualization of the MAPK pathway using the KEGG database

Supporting image 3

Disclosures: E. Eloseily: None; A. Pickering: None; S. Dhakal: None; H. Brunner: AbbVie, 2, AstraZeneca-Medimmune, 2, Biogen, 2, Boehringer-Ingelheim, 2, Bristol-Myers Squibb (BMS), 2, 5, Celgene, 2, Eli Lilly, 2, 5, EMD Serono, 2, F-Hoffman La Roche, 2, 5, GlaxoSmithKlein (GSK), 2, 5, 6, Horizon, 2, 2, Janssen, 5, Merck, 2, Novartis, 2, 5, 6, Pfizer, 2, 5, 6; S. Thornton: None; A. Grom: Novartis, 2, 5, Sobi, 2, 5.

To cite this abstract in AMA style:

Eloseily E, Pickering A, Dhakal S, Brunner H, Thornton S, Grom A. The Upregulation of MAP Kinase Pathway Genes Is Associated with Poor Treatment Response to Tofacitinib in Polyarticular Course Juvenile Idiopathic Arthritis [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/the-upregulation-of-map-kinase-pathway-genes-is-associated-with-poor-treatment-response-to-tofacitinib-in-polyarticular-course-juvenile-idiopathic-arthritis/. Accessed .

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