Biomarkers associated with anti-IL-36R antibody treatment in generalized pustular psoriasis

A method of monitoring a GPP patient's beneficial response and adjusting treatment for generalized pustular psoriasis (GPP) in a GPP patient experiencing an acute flare after administration of a single intravenous dose of an anti-interleukin-36 receptor antibody (anti-IL-36R antibody), comprising:

• a) obtaining, at baseline (pre-dose) and at weeks 1, 2 and/or 4 post-administration blood form the GPP patient;
• b) isolating plasma and quantifying in each time-point sample the expression level or concentration of at least three GPP biomarkers selected from pro-inflammatory processes (TNF, IL1B, IL6), neutrophil recruitment (CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, CXCR1, CXCR1, CXCR2), neutrophil occurrence (NCF1, NCF2, NCF4, ELANE) or in keratinocyte activation, differentiation and mediated inflammation transcripts (IL36A, IL36G, IL17C, IL19, IL20, IL22, IL24), CSF3, IL24, IL19, IL20, IL6, IL17C, IL12B, RN7SL471P, PTX3, MRGPRX3, LBP, CAMP, IL23A, RND1, ADAMTS4, SPOCD1, MRPL12, CXCL1, GOS2, SPATA20P1, SH2D5, SOCS3, PHLDA2, MGAM, SLC26A4, MMP9, PADI4, FOSL1, PDCD1, MT2A, SPRR2C, P2RY6, C2CD4A, OSM, IL1B, CYP27B1, PRSS22, FCGBP, LILRA5, SERPINA3, SNAI1, TGM2, CNGB1, MAMDC4, MT1G, JUNB, SOCS1 or CASP5 by a validated QPCR assay, ELISA, or other protein detection method
• c) computing, with a configured processor executing a pre-specified analysis pipeline, an activation z-score using pathway analysis at each post-dose time-point, the score comprising biomarker measurements relative to baseline;
• (d) classifying the patient as a responder when said biomarker score indicates ≥50% down-regulation relative to baseline at post-dose time-points;
• and
• (e) optionally adjusting treatment for the patient based on the classification, comprising administering an additional anti-IL-36R dose within 1-4 weeks.