Baricitinib-associated changes in global gene expression during a 24-week phase II clinical systemic lupus erythematosus trial implicates a mechanism of action through multiple immune-related pathways.

ABSTRACT:

Objective

To characterise the molecular pathways impacted by the pharmacologic effects of the Janus kinase (JAK) 1 and JAK2 inhibitor baricitinib in SLE.

Methods

In a phase II, 24-week, randomised, placebo-controlled, double-blind study (JAHH), RNA was isolated from whole blood in 274 patients and analysed using Affymetrix HTA2.0 array. Serum cytokines were measured using ultrasensitive quantitative assays.

Results

Gene expression profiling demonstrated an elevation of STAT1, STAT2 and multiple interferon (IFN) responsive genes at baseline in patients with SLE. Statistical and gene network analyses demonstrated that baricitinib treatment reduced the mRNA expression of functionally interconnected genes involved in SLE including STAT1-target, STA

SUBMITTER: Dorner T 

PROVIDER: S-EPMC7549481 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature