However, anaemia is aggravated by the myelosuppressive effects of pegylated interferon and the effect of ITPA polymorphisms on interferon-free treatments is unknown. We examined the effect of two ITPA SNPs on events associated with anaemia in patients treated with faldaprevir, BI 207127 and ribavirin in the SOUND-C2 study in which PLX4032 up to 85% of patients achieved SVR but >10% of patients experienced anaemia and 6% had ribavirin dose reductions. Methods: In this open-label Phase 2b study, 362 treatment-naive patients with genotype 1 HCV were randomised.
Two SNPs within the ITPA gene region, rs1127354 and rs6051702, were genotyped by melting curve analysis in 314 patients. ITPA genotypes were defined as favourable (rs1127354 AA or AC and rs6051702 CC or CA) or unfavourable (rs1127354 CC and rs6051702 AA) in terms
of their association with haemolytic anaemia. Anaemia (haemoglobin <10 g/dL), ribavirin dose reduction and erythropoietin 5-Fluoracil ic50 use were assessed for patients with favourable and unfavourable SNPs. Results: The proportions of patients who experienced an event associated with anaemia based on ITPA SNPs are shown in the Table. ITPA SNP and genotype rs1127354 AA or AC ‘Favourable’ rs1127354 CC ‘Unfavourable’ rs6051702 CC or CA ‘Favourable’ rs6051702 AA ‘Unfavourable’ Unfavourable genotype at both positions (n = 45) (n = 269) (n = 112) (n = 202) (n = 189) *Anaemia as an adverse event as defined by investigators (not a laboratory event) More patients experienced anaemia with unfavourable versus favourable ITPA SNPs, while no significant differences were found for ribavirin dose reductions or erythropoietin
use. The presence of unfavourable variants at both loci did not further increase the risk for anaemia, erythropoietin use or ribavirin dose reduction. Metalloexopeptidase Conclusions: While the overall risk of severe ribavirin-associated anaemia was low in the SOUND-C2 study, this preliminary analysis indicates that ITPA SNPs may be useful in predicting patients susceptible to ribavirin-induced anaemia during interferon-free treatment for HCV. 1. Fellay J, et al. Nature 2010;464(7287):405–408. S ZEUZEM,1 V SORIANO,2 T ASSELAH,3 J-P BRONOWICKI,4 AW LOHSE,5 B MÜLLHAUPT,6 M SCHUCHMANN,7 M BOURLIERE,8 M BUTI,9 S ROBERTS,10 ED GANE,11 J STERN,12 J-P GALLIVAN,13 W BÖCHER,13 F MENSA12 1Klinikum der J. W.
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