Background: A phase 3, randomized, double-blind, placebo-controlled, withdrawal, global efficacy, and safety trial was conducted in 20 countries (NCT03773978). The trial consisted of a 2-week safety and pharmacokinetic period, a 12-week open-label lead-in period and up to 32-week placebo-controlled double-blind withdrawal period. Patients received a once-daily 4 mg adult equivalent dose of baricitinib (tablets or suspension) in the open-label lead-in period. Patients meeting Juvenile Idiopathic Arthritis-American College of Rheumatology (JIA-ACR) 30 criteria (JIA-ACR30 responders) at the end of the open-label lead-in (week 12) were eligible for random assignment (1:1) to receive placebo or continue receiving baricitinib and remained in the double-blind withdrawal period until disease flare or up to the end of the double-blind withdrawal period (week 44). Baricitinib treatment resulted in a robust improvement in clinical response (JADAS-27) which was sustained over the randomized assignment period[1].

Objectives: Enrolled patients (aged 2 to <18 years) with polyarticular juvenile idiopathic arthritis (positive or negative for rheumatoid factor), extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis was investigated for longitudinal serum biomarker changes between week 0 (baseline) and week 12.

Methods: A total of 168 serum samples were analyzed (84 patients) using the 3072 O-link panel at both baseline and the 12-wk timepoint. All patients considered in these analyses had provided adequate informed consent for this exploratory biomarker study. Baricitinib-mediated pharmacodynamic changes in serum protein markers were measured as changes from baseline and were derived from a mixed model with repeated measurement (MMRM). Pearson correlation of the change in the serum biomarkers and the change in JADAS-27 scores, comparing baseline to the 12-week post treatment timepoint were reported. The proportional change form baseline for these serum markers were categorically identified across the 3 response sub-sets of JIA patients. These include JIA-ACR <30% (non-responders), 30-70% JIA-ACR response (responders), 70-100% JIA-ACR response (super-responders).

Results: Serum biomarkers were measured using the O-link explore 3072-panel at baseline and after 12-weeks of Baricitinib treatment. Changes in serum biomarkers were calculated using MMRM and were correlated with changes in clinical response (JADAS-27). The following biomarkers shown in Table 1 is a preliminary representation of the most significant serum marker changes in response to 12 weeks of treatment with baricitinib with all patients. These include known markers such as IL-6 which has been observed earlier in other indications such as RA and COVID-19[2]. In addition, several biomarkers pharmacodynamically modified by baricitinib are correlated with change in clinical response, such as JADAS-27.

Conclusion: This is the first of its kind study that measures serum protein markers in the context of an intervention trials with baricitinib in JIA patients. The summary of modified protein biomarkers and their correlation with clinical response will be discussed in detail. Notably, the association of such biomarker changes with clinical response and the categorical analyses of JIA-ACR response, may allow a physician to measure such markers in patients, to help reaffirm the clinical utility of baricitinib in JIA patients.

REFERENCES: [1] Ramanan, AV. et al, Lancet 2023; 402: 555–70.

[2] Sims, J. et al. J. Allergy Clin Immunol 2021;147:107-11.

Acknowledgements: NIL.

Disclosure of Interests: Venkatesh Krishnan Eli lilly, Eli lilly, Jonathan Sims Eli Lilly, Eli Lilly, Ching-Yun Chang Eli Lilly, Eli Lilly, Stuart Keller Eli Lilly, Eli Lilly, Rona Wang Eli Lilly, Eli Lilly, Maja Hojnik Eli Lilly, Eli Lilly, Robert Benschop Eli Lilly, Eli Lilly, Samuel Ogwu Eli Lilly, Eli Lilly, Christine Chew: None declared, Athimalaipet V. Ramanan Abbvie, Eli Lilly, SOBI, Pfizer, Roche, Novartis and UCB, Eli Lilly, Abbvie, Roche, Pfizer, UCB and Astra Zeneca, Novartis.