Interferon type I signature may predict non response upon rituximab in rheumatoid arthritis patients

Raterman HG et al. – This study demonstrates clinical utility for the use of baseline IFN type I response gene (IRG) expression levels as predictive biomarker for non–response to rituximab (RTX) in rheumatoid arthritis (RA).

Methods

• In 14 consecutive RA patients starting with RTX (test cohort), gene expression profiling on whole peripheral blood RNA was performed by Illumina HumanHT beadchip microarrays.
• Supervised cluster analysis (patients ranked on difference in 28 joints disease activity score (DAS28) after 6 months RTX) identified genes expressed differently at baseline in case of nonresponse (both deltaDAS28 < 1.2 and EULAR non–response).
• Genes of interest were measured by quantitative real–time PCR and tested for their predictive value using receiver operating characteristics (ROC) curves in an independent validation cohort (n = 26).

Results

• Genome–wide microarray analysis revealed a marked variation in the peripheral blood cells between RA patients before the start of RTX treatment.
• The authors demonstrated that only a cluster consisting of interferon (IFN) type I network genes, represented by a set of IFN type I response genes (IRGs), i.e. LY6E, HERC5, IFI44L, ISG15, MxA, MxB, EPSTI1 and RSAD2, was associated with deltaDAS28 and EULAR response outcome (P=0.0074 and P=0.0599, respectively).
• Based on the 8 IRGs an IFN–score was calculated that reached an AUC of 0.82 to separate non–responders from responders in an independent validation cohort of 26 patients using ROC curves analysis according to deltaDAS28<1.2 criteria.
• Advanced classifier analysis yielded a 3 IRG–set that reached an AUC of 87%.
• Comparable findings applied to EULAR non–response criteria.

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