In the Journals

Inclusive criteria, generic drugs effective for HCV in limited resource nations

Researchers from the University of Cairo analyzed the rates of sustained virologic response among patients with hepatitis C in Egypt since the introduction of direct-acting antivirals to share data on the planning and prioritization of treatment in a nation with limited resources and high prevalence of HCV.

Prioritization based on fibrosis stage was not effective and enrollment for DAA therapy increased once the program included all stages of fibrosis. Additionally, the availability of generic drugs reduced costs and helped increased enrollment in the program.

“Despite these successes and the high SVR rate with most treatment regimens used, the program faced several difficulties that caused backlogs and delays, were not anticipated, and had to be managed as they occurred,” Aisha Elsharkawy, MD, from the University of Cairo, and colleagues wrote. “The Egyptian national program for treating hepatitis C can thus send several messages and share several limitations with countries of similar settings. Avoiding them when starting treatment programs in similar settings would save time and resources.”

The study included 337,042 patients with hepatitis C who received treatment between October 2014 and March 2016. The researchers included patients with hepatitis B or HIV coinfection, those who had undergone liver transplantation, and those with severe extrahepatic manifestations.

In their analysis, the researchers categorized patients into three equal time periods of 6 months according to the standard DAA therapy in use:

Cohort 1: 120,407 patients treated between October 2014 and March 2015;

Cohort 2: 159,750 patients treated between April 2015 and 2015; and

Cohort 3: 56,885 patients treated between October 2015 and the end of March 2016.

From October 2014 to May 2015, the available DAA regimens included sofosbuvir with ribavirin or sofosbuvir with ribavirin and pegylated interferon.

“With limited financial resources, limited initial supply of medication, and limited capacities of treatment centers to handle the huge number of patients living with the diagnosis,” the researchers wrote, “there was a need to initially prioritize treatment to include patients with advanced fibrosis and to postpone treatment for patients with less advanced disease.”

After May 2015, however, it became apparent that the prioritization of patients by fibrosis stage resulted in a large backlog of patients waiting for treatment. This led to administrative and moral difficulties, according to the researchers. Additionally, more drugs became available, including simeprevir and daclatasvir.

At this time, the program shifted to include all patients regardless of fibrosis stage. The new protocol categorized patients into two groups. “Easy-to-treat” patients without cirrhosis who were treatment naive received sofosbuvir and daclatasvir, whereas “difficult-to-treat” patients with cirrhosis and treatment experience received sofosbuvir and daclatasvir with ribavirin.

Final outcomes

Patients in cohort 1 were more likely to have received treatment with interferon than those in cohort 2 or 3 (18.9% vs. 6.8%; P < .01) and had higher levels of baseline alanine aminotransferase, aspartate aminotransferase, bilirubin, international normalized ratio and alpha-fetoprotein, and lower levels of platelets and albumin.

The SVR rate for all 337,042 treated patients was 28%. The rate increased from 15.1% in cohort 1 to 67.7% in cohort 3. Among a subgroup analysis of 94,258 patients treated in the two months after cohort 3’s time period, the SVR rate increased up to 75.4%.

The combination of sofosbuvir with ribavirin for 24 weeks had the lowest SVR rate at 12 weeks (82.6%) compared with sofosbuvir with ribavirin and PEG-IFN (93.3%), sofosbuvir with simeprevir (97.4%), sofosbuvir with daclatasvir (97.8%) and sofosbuvir with daclatasvir and ribavirin (97.6%).

The presence of diabetes, hypertension, HBV surface antigen or HIV coinfection, and history of hepatocellular carcinoma, chemotherapy or liver transplantation did not impair therapy response.

The researchers also observed that generic drugs correlated with higher SVR rate (98.4%) compared with the brand medications.

“Cheap generic alternatives are effective, were the reason for the large number of patients treated, and are a suitable option for countries of similar limited resources,” the researchers wrote.

“The program has been cost-driven, and guidelines were repeatedly modified with the availability of cheaper and generic medications. The cost of diagnostics, on the other hand, remains an important part of the total cost to the program, and will remain a problem as long as there are no cheaper or generic alternatives,” Elsharkawy and colleagues concluded. “Simplifying the current testing schedule is essential and will result in significant saving.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.

Researchers from the University of Cairo analyzed the rates of sustained virologic response among patients with hepatitis C in Egypt since the introduction of direct-acting antivirals to share data on the planning and prioritization of treatment in a nation with limited resources and high prevalence of HCV.

Prioritization based on fibrosis stage was not effective and enrollment for DAA therapy increased once the program included all stages of fibrosis. Additionally, the availability of generic drugs reduced costs and helped increased enrollment in the program.

“Despite these successes and the high SVR rate with most treatment regimens used, the program faced several difficulties that caused backlogs and delays, were not anticipated, and had to be managed as they occurred,” Aisha Elsharkawy, MD, from the University of Cairo, and colleagues wrote. “The Egyptian national program for treating hepatitis C can thus send several messages and share several limitations with countries of similar settings. Avoiding them when starting treatment programs in similar settings would save time and resources.”

The study included 337,042 patients with hepatitis C who received treatment between October 2014 and March 2016. The researchers included patients with hepatitis B or HIV coinfection, those who had undergone liver transplantation, and those with severe extrahepatic manifestations.

In their analysis, the researchers categorized patients into three equal time periods of 6 months according to the standard DAA therapy in use:

Cohort 1: 120,407 patients treated between October 2014 and March 2015;

Cohort 2: 159,750 patients treated between April 2015 and 2015; and

Cohort 3: 56,885 patients treated between October 2015 and the end of March 2016.

From October 2014 to May 2015, the available DAA regimens included sofosbuvir with ribavirin or sofosbuvir with ribavirin and pegylated interferon.

“With limited financial resources, limited initial supply of medication, and limited capacities of treatment centers to handle the huge number of patients living with the diagnosis,” the researchers wrote, “there was a need to initially prioritize treatment to include patients with advanced fibrosis and to postpone treatment for patients with less advanced disease.”

After May 2015, however, it became apparent that the prioritization of patients by fibrosis stage resulted in a large backlog of patients waiting for treatment. This led to administrative and moral difficulties, according to the researchers. Additionally, more drugs became available, including simeprevir and daclatasvir.

At this time, the program shifted to include all patients regardless of fibrosis stage. The new protocol categorized patients into two groups. “Easy-to-treat” patients without cirrhosis who were treatment naive received sofosbuvir and daclatasvir, whereas “difficult-to-treat” patients with cirrhosis and treatment experience received sofosbuvir and daclatasvir with ribavirin.

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Final outcomes

Patients in cohort 1 were more likely to have received treatment with interferon than those in cohort 2 or 3 (18.9% vs. 6.8%; P < .01) and had higher levels of baseline alanine aminotransferase, aspartate aminotransferase, bilirubin, international normalized ratio and alpha-fetoprotein, and lower levels of platelets and albumin.

The SVR rate for all 337,042 treated patients was 28%. The rate increased from 15.1% in cohort 1 to 67.7% in cohort 3. Among a subgroup analysis of 94,258 patients treated in the two months after cohort 3’s time period, the SVR rate increased up to 75.4%.

The combination of sofosbuvir with ribavirin for 24 weeks had the lowest SVR rate at 12 weeks (82.6%) compared with sofosbuvir with ribavirin and PEG-IFN (93.3%), sofosbuvir with simeprevir (97.4%), sofosbuvir with daclatasvir (97.8%) and sofosbuvir with daclatasvir and ribavirin (97.6%).

The presence of diabetes, hypertension, HBV surface antigen or HIV coinfection, and history of hepatocellular carcinoma, chemotherapy or liver transplantation did not impair therapy response.

The researchers also observed that generic drugs correlated with higher SVR rate (98.4%) compared with the brand medications.

“Cheap generic alternatives are effective, were the reason for the large number of patients treated, and are a suitable option for countries of similar limited resources,” the researchers wrote.

“The program has been cost-driven, and guidelines were repeatedly modified with the availability of cheaper and generic medications. The cost of diagnostics, on the other hand, remains an important part of the total cost to the program, and will remain a problem as long as there are no cheaper or generic alternatives,” Elsharkawy and colleagues concluded. “Simplifying the current testing schedule is essential and will result in significant saving.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.