Dipeptidyl peptidase-4 (DPP-4) may predict response to tralokinumab in patients with asthma

RATIONALE: We sought biomarkers to identify asthma patients (pts) likely to benefit from tralokinumab, an anti–IL-13 IgG4 monoclonal antibody. METHODS: Airway epithelial cells grown in air-liquid interface cultures were stimulated with cytokines with/without dexamethasone for 24 hrs. Bronchial brushings with matched BAL and serum samples were collected from healthy volunteers (N=20) and asthma pts on ICS/LABA (N=68) or ICS/LABA+OCS (N=22). Serum DPP-4 was assessed with a new immunoassay (Abbott Diagnostics). Predictive utility of baseline serum DPP-4 was assessed using samples from a Ph IIb tralokinumab trial (NCT01402986). Consenting pts (N=300) were genotyped for DPP4 SNPs (N=89) and tested for association with serum DPP-4. RESULTS: DPP-4 mRNA expression was induced by IL-13 (20 fold, p p =0.03), FeNO (r=0.6, p =0.02) and serum DPP-4 (r=0.4, p =0.03). Above median concentrations of baseline serum DPP-4 from a Ph IIb trial were significantly predictive of exacerbation rate reduction, improvement in FEV 1 , ACQ-6, and AQLQ assessed at Week 52 on tralokinumab (table). Fourteen SNPs within or flanking DPP4 were associated with serum DPP-4 protein levels (unadjusted p CONCLUSIONS: Serum DPP-4 is a novel predictive biomarker for tralokinumab, which is in Ph III trials for severe asthma.