Effectiveness of Paritaprevir/Ritonavir, Ombitasvir, + Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C in Romania

Sustained virologic response was defined as hepatitis C virus ribonucleic acid (HCV RNA) levels less than 50 IU/mL 12 weeks after the last dose of study drug.

Time frame: 12 weeks after the last dose of study drug (week 24 or 36 depending on the treatment regimen)

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype). Three participants with genotype 1 prescribed paritaprevir/r and ombitasvir instead of paritaprevir/r, ombitasvir and dasabuvir (3DAA) were excluded.

Treatment regimen was assigned by the physician according to local practice and label. Participants could receive three direct-acting antiviral (DAA) drugs (paritaprevir/ritonavir, ombitasvir, and dasabuvir) with or without RBV for 12 or 24 weeks.

Time frame: Baseline

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype).

The BMQ consists of 2 sections and 18 questions to screen for patients' beliefs, attitudes and concerns about their medication. The BMQ-Specific section comprises two 5-item subscales assessing the necessity of and concerns about the prescribed medication (Specific-Necessity and Specific-Concerns). The BMQ-General section comprises two 4-item subscales assessing beliefs that medicines are harmful and overused by doctors in general (General-Harm and General-Overuse). The 18 items are rated on a Likert scale from 1 (strongly disagree) to 5 (strongly agree). Each subscale score ranges from 1 to 5. High scores in the Specific-Concerns scale represent the notion that adverse reactions are potentially harmful when taking medication on a regular basis, and high scores in the Specific-Necessity scale indicate the patient's need to adhere to medication to maintain health. High scores in the General-Harm and General-Overuse scales represent an overall negative perception of medication.

Time frame: Baseline and end of treatment (week 12 or 24 depending on the treatment regimen)

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype) with available data at baseline and end of treatment.

The EQ-5D-5L is a health state utility instrument that evaluates preference for health status. The 5 items in the EQ-5D-5L comprise 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which are rated on 5 levels of severity (1: indicating no problem, 2: indicating slight problems, 3: indicating moderate problems, 4: indicating severe problems, 5: indicating extreme problems), and a separate visual analog scale (VAS). Responses to the 5 dimension scores were combined and converted into a single preference-weighted health utility index score by applying country-specific weights.The range for EQ-5D-5L index score is 0 to 1 where '0' is defined as a health state equivalent to being dead and '1' is full health.The higher the score the better the health status.

Time frame: Baseline, end of treatment (week 12 or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype) and with available data at baseline and each time point.

The EQ-5D-5L is a health state utility instrument that evaluates preference for health status. with a separate visual analog scale (VAS). The VAS assesses overall health on a scale from 0 (worst health imaginable) to 100 (best health imaginable).

Time frame: Baseline, end of treatment (week 12 or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype) and with available data at baseline and each time point.

PAM 13 is a measure used to assess the patient knowledge, skill, and confidence for self-management, consisting of 13 questions. Each of the 13 items can be answered with one of four possible response options, which are disagree strongly (1), disagree (2), agree (3), agree strongly (4). Scores were summed to calculate the overall raw score, then transformed to a scale with a theoretical range 0 to 100, based on calibration tables, with higher PAM scores indicating higher patient activation

Time frame: Baseline and end of treatment (week 12 or 24 depending on the treatment regimen)

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype) with available data at baseline and end of treatment.

The WPAI Hepatitis C V2.0 is an HCV specific questionnaire used to measure work absenteeism, work presenteeism, and daily activity impairment. Respondents were asked about time missed from work and time while at work during which productivity was impaired in the past seven days. Results of WPAI are expressed as a percentage of impairment from 0 to 100, with higher percentages indicating greater impairment and less productivity. Absenteeism indicates the percentage of work time missed due to health problems.

Time frame: Baseline, end of treatment (week 12 or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype). Participants who were employed with available data at baseline and each time point are included.

The WPAI Hepatitis C V2.0 is an HCV specific questionnaire used to measure work absenteeism, work presenteeism, and daily activity impairment. Respondents were asked about time missed from work and time while at work during which productivity was impaired in the past seven days. Results of WPAI are expressed as a percentage of impairment from 0 to 100, with higher percentages indicating greater impairment and less productivity. Presenteeism indicates the percentage of impairment while working due to health problems.

Time frame: Baseline, end of treatment (week 12 or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype). Participants who were employed with available data at baseline and each time point are included.

The WPAI Hepatitis C V2.0 is an HCV specific questionnaire used to measure work absenteeism, work presenteeism, and daily activity impairment. Respondents were asked about time missed from work and time while at work during which productivity was impaired in the past seven days. Results of WPAI are expressed as a percentage of impairment from 0 to 100, with higher percentages indicating greater impairment and less productivity. Total activity impairment (TAI) indicates the percentage of general (non-work) activity impairment due to health problems.

Time frame: Baseline, end of treatment (week 12 or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype) with available data at baseline and each time point.

The WPAI Hepatitis C V2.0 is an HCV specific questionnaire used to measure work absenteeism, work presenteeism, and daily activity impairment. Respondents were asked about time missed from work and time while at work during which productivity was impaired in the past seven days. Results of WPAI are expressed as a percentage of impairment from 0 to 100, with higher percentages indicating greater impairment and less productivity. Total work productivity impairment (TWP) indicates the percentage of overall work impairment due to health problems.

Time frame: Baseline, end of treatment (week 12 or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype). Participants who were employed with available data at baseline and each time point are included.

Concomitant medication other than for chronic hepatitis C used from the time when the decision was made to initiate treatment with paritaprevir/ritonavir and ombitasvir with or without dasabuvir until after the last dose.

Time frame: From first dose of study drug to end of treatment, 12 to 24 weeks depending on the treatment regimen

Population: Enrolled patients who received at least one dose of paritaprevir/ritonavir and ombitasvir with or without dasabuvir.

Time frame: From first dose of study drug through 30 days after last dose (16 or 28 weeks depending on the treatment regimen). The over all median (minimum, maximum) duration of treatment was 84 (28, 175) days.

Population: All enrolled participants who received at least one dose of paritaprevir/ritonavir and ombitasvir with or without dasabuvir.

Time frame: Baseline

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype).

Virologic response was defined as hepatitis C virus ribonucleic acid (HCV RNA) levels less than 50 IU/mL.

Time frame: End of treatment (week 12 or 24 depending on the treatment regimen)

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype).

SVR12 non-response was categorized according to the following: * On-treatment virologic failure (breakthrough \[at least one documented HCV RNA \< 50 IU/mL followed by HCV RNA ≥ 50 IU/mL during treatment\] or failure to suppress \[each measured on-treatment HCV RNA value ≥ 50 IU/mL\]); * Relapse, defined as HCV RNA \< 50 IU/mL at EOT followed by HCV RNA ≥ 50 IU/mL post-treatment in patients who completed treatment (not more than 7 days shortened); * Death; * Premature treatment discontinuation with no on-treatment virological failure; * Missing SVR12 data and/or none of the above criteria.

Time frame: 12 weeks after the last dose of study drug (week 24 or 36 depending on the treatment regimen)

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype).

Sustained virologic response was defined as hepatitis C virus ribonucleic acid (HCV RNA) levels less than 50 IU/mL 12 weeks after the last dose of study drug. The core population with sufficient follow-up data regarding SVR12 included all core population participants who * had evaluable HCV RNA data ≥ 70 days after the last actual dose of paritaprevir/ritonavir, ombitasvir and dasabuvir * or a HCV RNA value ≥ 50 IU/mL at the last measurement post-baseline * or had HCV RNA \< 50 IU/mL at the last measurement post-baseline, but no HCV RNA measurement ≥ 70 days after the last actual dose of paritaprevir/ritonavir, ombitasvir with dasabuvir due to reasons related to safety (e.g. dropped out due to adverse event) or virologic failure.

Time frame: 12 weeks after the last dose of study drug (week 24 or 36 depending on the treatment regimen)

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype), and with sufficient follow-up data regarding SVR12.

Breakthrough was defined as at least one documented HCV RNA \< 50 IU/mL followed by HCV RNA ≥ 50 IU/mL during treatment.

Time frame: 12 or 24 weeks (depending on the treatment regimen)

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype) with virological response on-treatment and with at least one on-treatment measurement (including EOT) thereafter.

Relapse was defined as participants with a virologic response (VR; HCV RNA \< 50 IU/mL) at end of treatment (EOT) followed by HCV RNA ≥ 50 IU/mL at any time after the end of treatment.

Time frame: End of treatment (week 12 or 24 depending on the treatment regimen) and up to 24 weeks after the end of treatment.

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics, and with VR at EOT and who completed treatment, and had ≥ 1 HCV RNA measurement ≥ 70 days post-treatment and were a treatment failure between EOT and post-treatment day 70.

Time frame: From first dose of study drug to end of treatment, 12 to 24 weeks depending on the treatment regimen.

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype), who were prescribed ribavirin.

Adherence to study treatment was calculated as: Cumulative dose taken / (initial prescribed dose \* planned duration)

Time frame: From first dose of study drug to end of treatment, 12 to 24 weeks depending on the treatment regimen.

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype).

Adherence to study treatment was calculated as: Cumulative dose taken / (initial prescribed dose \* planned duration)

Time frame: From first dose of study drug to end of treatment, 12 to 24 weeks depending on the treatment regimen

Population: Enrolled participants who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype), who were prescribed ribavirin, and with available data.