Real World Evidence of the Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin and Patient Support Program in Patients With Chronic Hepatitis C

This was a prospective, multi-center observational study in participants receiving the interferon-free ABBVIE REGIMEN ± RBV in Israel. The prescription of a treatment regimen was at the discretion of the physician in accordance with local clinical practice and label, was made independently from this observational study and preceded the decision to offer the participant the opportunity to participate in this study. Adults chronically infected with HCV, receiving the interferon-free ABBVIE REGIMEN, were offered the opportunity to participate in this study during a routine clinical visit at the participating sites. Follow-up visits, treatment, procedures, and diagnostic methods followed physicians' routine clinical practice. Data were collected at the following time windows: baseline, early on-treatment visit, mid-treatment visit (for participants with a treatment duration of 24 weeks), end of treatment (EoT), early post-treatment and 12 and 24 weeks after the end of treatment (representing sustained virologic response 12 weeks after the end of treatment \[SVR12\] and sustained virologic response 24 weeks after the end of treatment \[SVR24\]).

• Ombitasvir/paritaprevir/ritonavir (Drug), also known as Ombitasvir also known as ABT-267, Paritaprevir also known as ABT-450: Co-formulated tablet
• Dasabuvir (Drug), also known as ABT-333: Tablet
• Ribavirin (Drug): Tablet
• Patient support program (Behavioral): Supportive services provided to participants included reminder calls, emails, text messages, a Care Coach, and educational/informational materials.

Primary outcomes

• Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [12 weeks after the last actual dose of study drug]: SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL 12 weeks after the last actual dose of study drug.

Secondary outcomes

• Percentage of Participants With Virologic Response at End of Treatment (EoT) [Up to 24 weeks]: Virologic response was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL at the end of treatment.
• Percentage of Participants With Sufficient Follow-up Who Achieved Sustained Virological Response 12 Weeks Posttreatment [12 weeks (at least 70 days) after the last actual dose of study drug]: 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 12 weeks after the last actual dose of study drug (CPSFU12) was defined as all participants who fulfilled one of the following criteria: * evaluable HCV RNA data ≥70 days after the last actual dose of the ABBVIE REGIMEN * an HCV RNA value ≥50 IU/mL at the last measurement post-baseline * HCV RNA <50 IU/mL at the last measurement post-baseline, but no HCV RNA measurement ≥70 days after the last actual dose of the ABBVIE REGIMEN due to reasons related to safety (e.g. dropped out due to AE) or virologic failure
• Percentage of Participants With Relapse [Up to 48 weeks after the last actual dose of study drug]: Relapse was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL at the end of treatment followed by HCV RNA level greater than or equal to 50 IU/mL.
• Percentage of Participants With Viral Breakthrough [Up to 24 weeks]: Viral breakthrough was defined as at least 1 documented hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL followed by HCV RNA level greater than or equal to 50 IU/mL during treatment.
• Percentage of Participants With On-treatment Virologic Failure [12 weeks after the last actual dose of study drug]: On-treatment virologic failure was defined as breakthrough (at least 1 documented hepatitis C virus ribonucleic acid (HCV RNA) less than 50 IU/mL followed by HCV RNA greater than or equal to 50 IU/mL during treatment) or failure to suppress (each measured on-treatment HCV RNA value greater than or equal to 50 IU/mL).
• Percentage of Participants Meeting Relapse Criteria [12 weeks after the last actual dose of study drug]: Relapse was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than 50 IU/mL at end of treatment or at the last on-treatment HCV RNA measurement followed by HCV RNA greater than or equal to 50 IU/mL post-treatment.
• Percentage of Participants Meeting Premature Study Drug Discontinuation Criteria [12 weeks after the last actual dose of study drug]: Premature study drug discontinuation was defined as participants who prematurely discontinued study drug with no on-treatment virologic failure.
• Percentage of Participants With Missing Sustained Virologic Response 12 Weeks Post-Treatment (SVR12) Data and/or Nonresponders Who Did Not Meet Specific SVR12 Nonresponder Criteria [12 weeks after the last actual dose of study drug]: The number of participants with missing SVR12 data or SVR12 nonresponder participants who did not meet criteria for on-treatment virologic failure, relapse, premature treatment discontinuation, and who did not have an Insufficient virological response reported was documented.

Sex: All, ages: 18 Years to any

* Treatment-naïve or -experienced adult male or female participants with confirmed chronic hepatitis C (CHC), genotype 1 or 4, receiving combination therapy with the interferon-free ABBVIE REGIMEN ± ribavirin (RBV) according to standard of care and in line with the current local label
* If RBV was co-administered with the ABBVIE REGIMEN, it had to be prescribed in line with the current local label (with special attention to contraception requirements and contraindication during pregnancy)
* Participants had to voluntarily sign and date an informed consent form prior to inclusion into the study
* Participants must not have participated or intended to participate in a concurrent interventional therapeutic trial

Exclusion Criteria:

\- None

Participant flow

Outcome results

• Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12) (Primary), Number, percentage of participants: Participants With HCV Genotype 1 or 4 70.6 (64.4 to 76.1)
• Percentage of Participants With Virologic Response at End of Treatment (EoT) (Secondary), Number, percentage of participants: Participants With HCV Genotype 1 or 4 82.0 (76.5 to 86.5)
• Percentage of Participants With Sufficient Follow-up Who Achieved Sustained Virological Response 12 Weeks Posttreatment (Secondary), Number, percentage of participants: Participants With HCV Genotype 1 or 4 95.8 (91.7 to 98.0)
• Percentage of Participants With Relapse (Secondary), Number, percentage of participants: Participants With HCV Genotype 1 or 4 0.0 (0.0 to 2.4)
• Percentage of Participants With Viral Breakthrough (Secondary), Number, percentage of participants: Participants With HCV Genotype 1 or 4 0.0 (0.0 to 3.7)
• Percentage of Participants With On-treatment Virologic Failure (Secondary), Number, percentage of participants: Participants With HCV Genotype 1 or 4 1.3
• Percentage of Participants Meeting Relapse Criteria (Secondary), Number, percentage of participants: Participants With HCV Genotype 1 or 4 0
• Percentage of Participants Meeting Premature Study Drug Discontinuation Criteria (Secondary), Number, percentage of participants: Participants With HCV Genotype 1 or 4 1.8
• Percentage of Participants With Missing Sustained Virologic Response 12 Weeks Post-Treatment (SVR12) Data and/or Nonresponders Who Did Not Meet Specific SVR12 Nonresponder Criteria (Secondary), Number, percentage of participants: Participants With HCV Genotype 1 or 4 25.9

Adverse events

Time frame: Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks).

Serious adverse events by term

Other adverse events by term

• Results publication: Ferenci P, Bourgeois S, Buggisch P, Norris S, Curescu M, Larrey D, Marra F, Kleine H, Dorr P, Charafeddine M, Crown E, Bondin M, Back D, Flisiak R. Real-world safety and effectiveness of ombitasvir/paritaprevir/ritonavir +/- dasabuvir +/- ribavirin in hepatitis C virus genotype 1- and 4-infected patients with diverse comorbidities and comedications: A pooled analysis of post-marketing observational studies from 13 countries. J Viral Hepat. 2019 Jun;26(6):685-696. doi: 10.1111/jvh.13080. Epub 2019 Mar 5. PMID 30739368

• Study Protocol (PDF, 2016-03-16)
• Statistical Analysis Plan (PDF, 2018-03-26)

• AbbVie Inc., Study director, AbbVie