An Observational Cohort Study in Patients With Chronic Hepatitis B Receiving Pegasys

Percentage of participants who became Hepatitis B Virus Surface Antigen (HBsAg) negative by the end of the observation period. A participant was considered to have achieved HBsAg clearance if the HBsAg measurement was reported as: (a) 'Negative' or (b) a quantitative result lower than the reported lower limit of detection. An observational period was upto 3 years post-treatment. The analysis was performed by 2 methods: Analysis A and Analysis B. For analysis A, all participants included in the analyzed population were used (participants with missing measurement for calculation of the endpoint were considered non-responders regarding the endpoint). For analysis B method, only participants in the analyzed population without missing measurements for calculation of the endpoint were used (analysis as observed).

Time frame: Up to 276 Weeks

Population: mITT population included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol. Data of participants available at the assessment time point were included in the analysis.

The probability that the participant who develops an early virological/serological response would achieve HBsAg clearance 3 years post-treatment is called the PPV of the early virological/serological response. The probability that the participant who fails to develop an early virological/serological response also would fail to achieve HBsAg clearance 3 years post-treatment is called the NPV of the early virological/serological response. The positive and negative predictive values of early response at Weeks 12 and 24 on achievement of HBsAg clearance at 3 years post-treatment were examined. The following evidence of early response was explored (giving both NPV and PPV): For HBeAg negative patients, any decline in HBsAg from baseline to Week 12 and 24 and at least a 10% decline in HBsAg from baseline to Weeks 12 and 24.

Time frame: Up to 276 Weeks

Population: mITT population included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol.

The probability that the participant who develops an early virological/serological response would achieve Hepatitis B Surface Antigen (HBsAg) clearance 3 years post-treatment is called the positive predictive value (PPV) of the early virological/serological response. The probability that the participant who fails to develop an early virological/serological response also would fail to achieve HBsAg clearance 3 years post-treatment is called the negative predictive value (NPV) of the early virological/serological response. The positive and negative predictive values of early response at Weeks 12 and 24 on achievement of HBsAg clearance at 3 years post-treatment were examined. The following evidence of early response was explored (giving both NPV and PPV): For HBeAg positive participant, HBsAg \<1,500 International Units Per Milliliter (IU/mL) and HBsAg \<20,000 IU/mL at Weeks 12 and 24.

Time frame: Up to 276 Weeks

Population: mITT population included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol. Data of participants available at the assessment time point were included in the analysis.

ALT ratio was calculated as serum ALT, divided by the upper limit of the normal range.

Time frame: Up to 276 Weeks

Population: mITT population included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol.

The clinical endpoint of deaths due to any cause during observation period is presented.

Time frame: Up to 276 Weeks

Population: Safety population was defined to include participants with informed consent who received at least one dose of peginterferon alfa-2a and had at least one post-baseline safety assessment (any assessment after baseline).

An Adverse Events (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes.

Time frame: Up to 276 Weeks

Population: Safety population was defined to include participants with informed consent who received at least one dose of PEG IFN and had at least one post-baseline safety assessment (any assessment after baseline).

Number of participants with clinical endpoints associated with CHB captured in the medical record, where data available, are reported. The clinical endpoints included development of cirrhosis (in participants without cirrhosis at baseline). The liver cirrhosis assessments were summarized from Week 12 to 3 years post-treatment.

Time frame: Up to 276 Weeks

Population: mITT included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol.

Number of clinical endpoints associated with CHB reported in the medical record, where data available, are reported. The clinical endpoints included liver transplantation, hepatocellular carcinoma, liver decompensation, development of cirrhosis (in patients without cirrhosis at baseline).

Time frame: Up to 276 Weeks

Population: mITT population included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol.

Non serious adverse drug reactions (NSADRs) are all noxious and unintended responses to a medicinal product related to any dose.

Time frame: Up to 276 Weeks

Population: Safety population was defined to include participants with informed consent who received at least one dose of PEG IFN and had at least one post-baseline safety assessment (any assessment after baseline).

A serious adverse drug reactions (SADR) is any untoward medical occurrence suspected to be medicinal product-related that at any dose: Results in death, is life-threatening, NOTE: The term life-threatening in the definition of serious refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe. Requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or Is a congenital anomaly/birth defect.

Time frame: Up to 276 Weeks

Population: Safety population was defined to include participants with informed consent who received at least one dose of PEG IFN and had at least one post-baseline safety assessment (any assessment after baseline).

Hepatitis B surface antigen (HBsAg) is a viral protein detectable in the blood in acute and chronic hepatitis B infection. A participant was considered to have achieved HBsAg seroconversion if (a) the participant achieved HBsAg clearance and (b) the last approved anti-HBs measurement in the analyzed time window was reported as i) 'POSITIVE' or (ii) quantitative result and was greater than or equal to the reported lower limit of detection.

Time frame: Up to 276 Weeks

Population: mITT population included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol.

A participant was considered to have achieved HBeAg loss if the HBeAg measurement was reported as (a) 'NEGATIVE' or (b) a quantitative result was lower than the reported lower detection limit. This endpoint was measured in the participants with HBeAg positive CHB.

Time frame: Up to 276 Weeks

Population: mITT population included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol.

A participant was considered to have achieved HBeAg seroconversion and suppression of HBV DNA to \<2,000 IU/mL if (a) the participant achieved HBeAg seroconversion and (b) the participant achieved suppression of HBV DNA to \<2,000 IU/mL. If a patient received NUCs after end of PEG IFN treatment, then a reported suppression of HBV DNA to \< 2,000 IU/mL during or after this NUC treatment were to be ignored, and HBV DNA ≥ 2,000 IU/mL was to be assigned. However, HBV DNA \< 2,000 IU/mL was not to be ignored, if the NUC treatment given parallel to PEG IFN was discontinued within the first 8 weeks after end of PEG IFN treatment and prior to the HBV DNA value concerned no further NUCs were administered. Abbreviations for Seroconversion=sercnvrsn, Analysis A= AnalysA, and Analysis B= AnalysB, pt=post-treatment.

Time frame: Up to 276 Weeks

Population: mITT population included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol.

HBeAg seroconversion is presented as percentage of participants who become HBeAg negative and anti-HBe positive. A participant was considered to have achieved HBeAg seroconversion if (a) the participant achieved HBeAg loss and (b) the anti-HBe measurement was reported as (i) 'POSITIVE' or (ii) a quantitative result considered 'positive' in the context. HBeAg seroconversion and suppression of HBV DNA to \<2,000 IU/mL: A participant was considered to have achieved HBeAg seroconversion and suppression of HBV DNA to \<2,000 IU/mL if (a) the participant achieved HBeAg seroconversion and (b) the participant achieved suppression of HBV DNA to \<2,000 IU/mL. Abbreviations for pt=post-treatment.

Time frame: Up to 276 Weeks

Population: mITT population included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol.

A participant was considered to have achieved normalization of alanine transaminase (ALT) if the ALT measurement was lower or equal to the upper limit of the normal range. Only patients with elevated ALT at baseline were included in any analyses where normalization of ALT was used as endpoint. It was analyzed as last serum ALT in the analyzed time window, divided by the upper limit of the normal range.

Time frame: Up to 276 Weeks

Population: mITT included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol.

A participant was considered to have achieved suppression of Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) to \<2,000 International Units Per Milliliter (IU/mL) if the HBV DNA measurement is lower than 2,000 IU/mL.

Time frame: Up to 276 Weeks

Population: mITT population included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol.

Quantitative HBsAg assay is a diagnostic test for assessing the amount of the HBsAg in chronic hepatitis B participants. Last approved quantitative HBsAg measurement in the analyzed time window.

Time frame: Up to 276 Weeks

Population: mITT population included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol.