Biomarker Changes in Response to Tofacitinib Treatment in Patients with Polyarticular Course Juvenile Idiopathic Arthritis

Ekemini A Ogbu; Hermine I Brunner; Esraa Eloseily; Yonatan Butbul Aviel; Kabita Nanda; Heinrike Schmeling; Heather Tory; Yosef Uziel; Diego Oscar Viola; Dawn M Wahezi; Stacey E Tarvin; Alyssa Sproles; Chen Chen; Nicolino Ruperto; Bin Huang; Alexei Grom; Sherry Thornton; investigators of the PRINTO and PRCSG networks

doi:10.1002/acr.25417

Biomarker Changes in Response to Tofacitinib Treatment in Patients with Polyarticular Course Juvenile Idiopathic Arthritis

Arthritis Care Res (Hoboken). 2024 Aug 12. doi: 10.1002/acr.25417. Online ahead of print.

Authors

Ekemini A Ogbu^{1

2

3}, Hermine I Brunner^{1

2}, Esraa Eloseily^{1

4}, Yonatan Butbul Aviel⁵, Kabita Nanda⁶, Heinrike Schmeling⁷, Heather Tory^{8

9}, Yosef Uziel¹⁰, Diego Oscar Viola¹¹, Dawn M Wahezi¹², Stacey E Tarvin¹³, Alyssa Sproles¹⁴, Chen Chen¹, Nicolino Ruperto¹⁵, Bin Huang¹, Alexei Grom^{1

14}, Sherry Thornton^{1

14}; investigators of the PRINTO and PRCSG networks

Collaborators

investigators of the PRINTO and PRCSG networks:
Sanjeev Dhakal, Angela Merritt, Megan Quinlan-Waters

Affiliations

¹ Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
² University of Cincinnati College of Medicine, Cincinnati, OH, USA.
³ Johns Hopkins University, Baltimore, MD, USA.
⁴ Assiut University Faculty of Medicine, Assiut, Egypt.
⁵ Rambam Health Care Campus, Haifa, Israel.
⁶ Seattle Children's Hospital and University of Washington School of Medicine.
⁷ Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
⁸ University of Connecticut School of Medicine, Farmington, CT.
⁹ Connecticut Children's Medical Center, Hartford, CT.
¹⁰ Meir Medical Center, Kfar-Saba, Tel Aviv School of Medicine, Tel Aviv University, Israel.
¹¹ Instituto CAICI SRL, Rosario, Argentina.
¹² Children's Hospital at Montefiore, Bronx, NY, USA.
¹³ Riley Hospital for Children at Indiana University, Indianapolis, IN, USA.
¹⁴ Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA.
¹⁵ IRCCS Istituto Giannina Gaslini, Servizio Sperimentazioni Cliniche Pediatriche/Gaslini Trial Centre, PRINTO, Genoa, Italy (NR).

PMID: 39135452
DOI: 10.1002/acr.25417

Abstract

Objective: Examine levels of candidate blood-based biomarkers (CBB) in juvenile idiopathic arthritis (JIA) treated with tofacitinib.

Methods: JIA patients who participated in clinical trial NCT02592434 received tofacitinib from baseline to week 18. Serial serum samples were assayed for CBB (S100A8/9, S100A12, IL-18, SAA, resistin, VEGF, Angiopoietin-1, Angiopoietin-2, MMP8, MMP2, TIMP1, Leptin, CXCL9, sIL2R, ICAM-1, sTNFr, IL-6, IL-23, MCP1, CCL18, and CCL20). Association of CBB with JIA response to treatment from baseline to week 18 were assessed.

Results: This study included 166 patients with polyarticular-course JIA. Paired serum samples from 143 patients were available at both baseline and week 18. There were 35% (50/143) of patients with a JIA-American College of Rheumatology 90 (JIA-ACR90) level improvement while 90/121/137 (63%/85%/96%) achieved JIA-ACR70/50/30 improvement at wk18. Despite small numerical differences by JIA category, there were no baseline CBB values that independently predicted a decrease in JADAS-27 or JIA-ACR90 response by week 18. Decrease in resistin level (baseline to week 18) was significantly associated with wk18 improvement in JADAS-27 and JIA-ACR90 response, after adjusting for age, sex, JIA disease duration and baseline resistin [(r² 0.79, SE, 0.070, p<0.01 and OR(95%CI) = 1.134(1.018, 1.264)]. HLA-B27 positivity was significantly associated with not achieving a JIA-ACR90 response at week 18 (p=0.0097).

Conclusion: Among the CBB included, only resistin was significantly associated with treatment response, and no CBB was identified that forecasts JIA improvement after initiation of tofacitinib. The association of HLA-B27 positivity with lower response to tofacitinib in JIA is intriguing and merits further study.