IL28B CC genotype is associated with higher on-treatment-response rates in pts with HCV-3: interim results of the WRITE study

Background: First generation DAA have been shown no active against HCV-3. Therefore, PegIFN and RBV will remain for few many years the SOC for HCV-3. Aims: To prospectively evaluate, in pts with HCV-2 and-3, differences in treatment response rates by both IL28B genotype and RBV dosages. Methods: Pts were stratified by HCV genotype and randomized 3:3:1 to PegIFNα-2a plus weight-based RBV for 12 or 24 wks according to RVR (Arm A), fixed 800 mg of RBV for 12 or 48 wks according to RVR (Arm B), or fixed 800 mg of RBV for 24 wks (Arm C). IL28B rs12979860 was tested by TaqMan allelic discrimination kit (Applied Biosystems). On-treatment-response was assessed by Roche TaqMan using the threshold of 25 IU/ml. Results: 503 pts are so far available for the planned week-12 interim analysis. HCV and IL28B genotypes distribution in these pts are shown in the table. Overall 35% of pts attained VRVR, and 68%, RVR. In HCV-2, rates of both VRVR and RVR were higher than in HCV-3 (44% vs 26%, and 76% vs 63%, p< 0.04). Of 227 pts enrolled to weight-based dosages of RBV (Arm A) 71% attained RVR as compared to 66% out of the remaining pts analyzed lumping together Arms B and C, (p=0.10). The corresponding EVR rates were 84% and 82%, respectively. When pts were analyzed by IL28B, rates of RVR in pts with HCV-3 and CC genotype were higher than in nonCC (76% vs 59%, p=0.04). No differences were observed in HCV-2 pts. Higher dosages of RBV increase RVR rates only in HCV-3 CC pts (83% vs 58%, p=0.06). Independent predictors of RVR were absence of cirrhosis (OR=3.1, 95% C.I.1.62-5.93) and IL28BCC (OR =1.9, 95% C.I.1.04-3.40). Conclusions: Higher RBV dosages may be required by HCV-3 pts to obtain RVR even in the presence of IL28BCC. Cirrhosis and nonCC genotype are negative modulator of RVR. HCV3 (n=303) HCV3 by IL28BCC (n=107) HCV2 (n=200) HCV2 by IL28BCC (n=75) ARM-A (n=227) 133 42 94 46 ARM-B (n=200) 122 52 78 22 ARM-C (n=76) 48 13 28 7 [IL28BCC distribution by HCV genotypes ]