In the Journals

Elbasvir/grazoprevir effective against HCV in those with blood disorders

Combination therapy with elbasvir/grazoprevir achieved sustained virologic response at 12 weeks in patients with inherited blood disorders, according to a prospective study.

“Patients with [inherited blood disorders] are living longer due to improvements in their specialized medical care, but remain at risk for the significant morbidity and mortality (such as end-stage liver disease and hepatocellular carcinoma) associated with HCV infection,” the researchers wrote. “While improvements in blood banking procedures have led to almost no transfusion-associated HCV infections in Western countries, HCV contaminated blood products continue to contribute new cases of HCV infection in resource-constrained settings.”

The C-EDGE IBLD phase 3 study included 159 patients with HCV and sickle cell anemia, thalassemia, hemophilia A/B or von Willebrand disease divided into two cohorts. The immediate treatment group (ITG) of 107 patients received elbasvir/grazoprevir (Merck) for 12 weeks and the delayed treatment group (DTG) of 52 patients received placebo for 12 weeks followed by 4 weeks of elbasvir-grazoprevir. Both groups were followed for 24 weeks after treatment.

At 12 weeks, 100 patients achieved SVR. Of the seven patients who did not, six patients relapsed and one was lost to follow-up. Forty-six of the 100 successful cases had undetectable HCV RNA of less than 15 IU/mL by week 2, followed by 90 patients at week 4 and all 100 at week 12.

Four patients of the 47 who had HCV genotype 1a also had NS5A resistance-associated substitutions (RASs) at positions 28, 30, 31 or 93 and NS3 RASs at baseline. SVR was achieved by one of these patients and by 42 of the 43 patients with no baseline NS5A RASs.

The safety profile was comparable between the two groups with the most frequent adverse events being headache, fatigue, nausea and asthenia. The serious adverse events observed in the ITG included one patient with thalassemia and erosive gastritis and hypophosphatemia, one patient with sickle cell disease with crisis and one patient with hemophilia A and rectal hemorrhage. In the DTG, serious adverse events were observed in six patients including sickle cell disease with crisis, sickle cell disease with crisis and anemia, fall, increased alanine aminotransferase alanine transaminase/aspartate transaminase, osteonecrosis and chronic myeloid leukemia.

“Laboratory assessments of hemoglobin and clotting parameters were similar in both the ITG and DTG. For the duration of treatment, hemoglobin levels and international normalized ratio values were similar in patients receiving [elbasvir/grazoprevir] and placebo. Among patients with hemoglobinopathies (sickle cell disease and [beta]-thalassemia), the on-treatment change in mean hemoglobin levels was also similar in patients receiving [elbasvir/grazoprevir] compared with those receiving placebo,” the researchers wrote. – by Talitha Bennett

 

Disclosure : Hézode reports personal fees from AbbVie, Bristol-Myers Squibb, Gilead, Janssen and Merck. Please see the full study for the other researchers’ relevant financial disclosures.

Combination therapy with elbasvir/grazoprevir achieved sustained virologic response at 12 weeks in patients with inherited blood disorders, according to a prospective study.

“Patients with [inherited blood disorders] are living longer due to improvements in their specialized medical care, but remain at risk for the significant morbidity and mortality (such as end-stage liver disease and hepatocellular carcinoma) associated with HCV infection,” the researchers wrote. “While improvements in blood banking procedures have led to almost no transfusion-associated HCV infections in Western countries, HCV contaminated blood products continue to contribute new cases of HCV infection in resource-constrained settings.”

The C-EDGE IBLD phase 3 study included 159 patients with HCV and sickle cell anemia, thalassemia, hemophilia A/B or von Willebrand disease divided into two cohorts. The immediate treatment group (ITG) of 107 patients received elbasvir/grazoprevir (Merck) for 12 weeks and the delayed treatment group (DTG) of 52 patients received placebo for 12 weeks followed by 4 weeks of elbasvir-grazoprevir. Both groups were followed for 24 weeks after treatment.

At 12 weeks, 100 patients achieved SVR. Of the seven patients who did not, six patients relapsed and one was lost to follow-up. Forty-six of the 100 successful cases had undetectable HCV RNA of less than 15 IU/mL by week 2, followed by 90 patients at week 4 and all 100 at week 12.

Four patients of the 47 who had HCV genotype 1a also had NS5A resistance-associated substitutions (RASs) at positions 28, 30, 31 or 93 and NS3 RASs at baseline. SVR was achieved by one of these patients and by 42 of the 43 patients with no baseline NS5A RASs.

The safety profile was comparable between the two groups with the most frequent adverse events being headache, fatigue, nausea and asthenia. The serious adverse events observed in the ITG included one patient with thalassemia and erosive gastritis and hypophosphatemia, one patient with sickle cell disease with crisis and one patient with hemophilia A and rectal hemorrhage. In the DTG, serious adverse events were observed in six patients including sickle cell disease with crisis, sickle cell disease with crisis and anemia, fall, increased alanine aminotransferase alanine transaminase/aspartate transaminase, osteonecrosis and chronic myeloid leukemia.

“Laboratory assessments of hemoglobin and clotting parameters were similar in both the ITG and DTG. For the duration of treatment, hemoglobin levels and international normalized ratio values were similar in patients receiving [elbasvir/grazoprevir] and placebo. Among patients with hemoglobinopathies (sickle cell disease and [beta]-thalassemia), the on-treatment change in mean hemoglobin levels was also similar in patients receiving [elbasvir/grazoprevir] compared with those receiving placebo,” the researchers wrote. – by Talitha Bennett

 

Disclosure : Hézode reports personal fees from AbbVie, Bristol-Myers Squibb, Gilead, Janssen and Merck. Please see the full study for the other researchers’ relevant financial disclosures.