Management of Hemoglobin Decrease in Patients Treated With ABT-450/Ritonavir/Ombitasvir and Dasabuvir With or Without Ribavirin in HCV Genotype 1-Infected Patients

Abstract

Introduction: Ribavirin (RBV), which may be associated with anemia, is commonly prescribed with direct-acting antivirals for treatment of hepatitis C virus (HCV) infection. The phase 3 PEARL trials evaluated the safety and efficacy of ABT-450/ritonavir/ombitasvir (formerly ABT-267) and dasabuvir (formerly ABT-333) with or without RBV in HCV genotype 1b-infected treatment-experienced (PEARLII) or treatment-naïve (PEARL-III) patients, and in genotype 1a-infected treatment-naïve (PEARL-IV) patients. Methods: The management of decreased hemoglobin was determined using data from the 910 patients enrolled in PEARL-II (n=186), PEARL-III (n=419), and PEARL-IV (n=305) trials. In each trial, HCV genotype 1-infected patients were randomized to 12 weeks of treatment with 3D+RBV (co-formulated ABT-450/r/ombitasvir [150 mg/100 mg/25 mg once a day] and dasabuvir [250 mg twice a day] with weight-based RBV [1,000 or 1,200 mg daily divided twice a day]), or 3D+placebo for RBV (PEARLIII and -IV) or 3D without RBV (PEARL-II). Hemoglobin was assessed at baseline and throughout treatment and follow-up periods. Decreases in hemoglobin during treatment and patient outcomes are reported. Results: Among patients with normal baseline hemoglobin values, on-treatment grade 2 hemoglobin decrease (8 to ≤10 g/dL) occurred in 23 patients (5.7%) receiving 3D+RBV; grade 3 decrease (6.5 to ≤8 g/dL) occurred in 2 patients (0.5%). No patients receiving 3D without RBV experienced grade 2 or greater hemoglobin decrease while on treatment. There were no grade 4 hemoglobin decreases (<6.5 g/dL). RBV dose was reduced in 23 patients (5.7%) to manage anemia or hemoglobin decrease; all patients with RBV dose modification achieved SVR12. Mean hemoglobin values decreased by the second week of treatment, and returned to near-baseline by 4 weeks post-treatment. One patient (0.1%) received a blood transfusion for hemoglobin <8 g/dL. No erythropoietin use was required. No patient discontinued the study due to decreased hemoglobin. Conclusion: The 3D regimen was well tolerated with and without RBV. Clinically significant decreases in hemoglobin were uncommon. Hemoglobin levels <10 g/dL were managed successfully with RBV dose modification, without impact on treatment response. Disclosure - V Rustgi - Grant/Research Support: Abbvie, Gilead, BMS; Speaker’s Bureau: Gilead, Genentech, Janssen; Advisory Boards: Abbvie, Gilead, Janssen. D Bernstein - Grant/Research support: AbbVie, BMS, Gilead, Janssen, Vertex, Merck, Genentech; Consultant/Speaker’s Bureau: AbbVie, Gilead, Janssen, Vertex, Merck. T Sepe - Research support: AbbVie. W King - Nothing to disclose. M Diago - Grant/Research Support: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Roche, MSD, Novartis, Vertex. Speaker’s Bureau: MSD, Roche, Janssen, BMS, Gilead Sciences. P Andreone - Advisory committees for Roche, Merck, Janssen Cilag, AbbVie, Boehringer Ingelheim, Gilead Sciences, and BMS; Consultant for Merck and BMS; Grant/Research Support from Roche, Merck, and Gilead Sciences. D Forton - Consultant: Abbvie, Roche, BMS, Merck, Boehringer Ingelheim, Gilead, Janssen; Grant/Research Support: Roche, Gilead. H Reesink - Consultant: AbbVie, Astex, BMS, Gilead Sciences, GSK, Janssen-Cilag, Merck, PRAInternational, Roche, Tibotec, R-Pharm, and Regulus; Grant/Research Support: AbbVie, BMS, Boehringer Ingelheim, Gilead Sciences, Janssen-Cilag, Merck, PRA-International, Roche, and Santaris. P Ferenci - Ad Board/Speaker’s Bureau: Roche, MSD, BMS, Gilead, Abbvie, Böehringer Ingelheim, Idenix, Janssen; Research/Grant Support: Roche. Y Hu - Employee/Stockholder: AbbVie. J Enejosa - Employee/Stockholder: AbbVie. D Cohen - Employee/Stockholder: AbbVie. Y Luo - Employee/Stockholder: AbbVie. M Pedrosa - Employee/Stockholder: AbbVie. J Vierling - Research support: Abbvie, Biotest, BMS, Gilead, Janssen, Vertex, Merck, Genentech, Genfit, Hyperion, Intercept, Ocera, Sundise. Advisory Boards: Abbvie, Boerhinger-Ingelheim, BMS, Gilead, Janssen, Merck, Hyperion, Intercept, Sundise. This research was supported by an industry grant from AbbVie.Table 1