Transcript IL28B in the Era of DAA Therapy: Ten Years Too Late

IL28B in the Era of DAA Therapy:
Ten Years Too Late?
Donald M. Jensen, MD
Professor of Medicine
Director, Center for Liver Disease
University of Chicago
IL28B in the Era of DAA Therapy:
What’s not to like?
• Can we avoid the toxicity of DAAs and use
dual therapy in IL28B CC patients?
• Is knowledge of IL28B CC status helpful in
encouraging patients to be treated with the
hope of eRVR+ RGT?
• Can we use IL28B TT or CT information in
patients with “mild” disease to wait for newer
therapies with better outcomes?
Dual versus Triple Therapy
• The argument: Dual therapy for IL28B CC is
more cost-effective than triple therapy:
– For patients with IL28B CC: SVR rates (~90%) are
about the same with P/R as if T/P/R was used right
from the start
– It is more cost-effective to treat IL28B CC subjects
initially with PEG/RBV and reserve TVR-based triple
therapy to those who do not respond.
Gellad et al: AASLD 2011
Dual versus Triple Therapy
• However,….
– This two step strategy means that at least 36% of patients
will require a subsequent course of triple therapy
– It assumes that 100% of P/R failures will undergo retreatment - not supported by clinical experience data.
– Evolution of therapy may demonstrate that these uniquely
responsive patients may achieve a comparably high rate of
SVR with only 12 weeks of triple therapy without the need
for a PEG/RBV tail (trial in progress)
– Finally, patients may refuse a non-DAA containing therapy
– But, if government or insurance mandated…….
Duration of Therapy: 24 vs 48 weeks
• The argument: Those with geno-1, IL28B CC
are more likely to have an eRVR and qualify for
24 weeks (RGT) therapy.
• However,….
– Regardless of IL28B status, an eRVR still requires
actual measurement of undetectable HCV RNA at
weeks 4 and 12
– It’s on-treatment virologic responses that really
matter, not pre-treatment dispositions
Selecting Candidates for Therapy
• Argument: IL28B CT or TT with ‘mild disease’
may be able to wait for future therapies
However,…
– How do we define ‘mild’? What is the accuracy?
• E.g. Liver bx: 25-30% may miss cirrhosis
• Surrogate testing not perfect either
– Could argue that all ‘mild’ cases be deferred given
the toxicity of DAA triple therapy, not just IL28B T?
– When is IFN-free therapy anticipated? 2014-2015?
Selecting Candidates for Therapy
• Argument: IL28B may identify a cohort of
uniquely sensitive subjects for short course
IFN-free therapy
However,….
– As therapies become more effective (>90% SVR),
the role of IL28B will decline as a predictor (e.g.
PILLAR)
– In the absence of IFN, will there even be a role for
l-IFN responsiveness? (e.g. PROTON)
Summary
• How will IL28B be utilized in the era of DAA
triple therapy?
– Predict shorter treatment duration
– Identify patients who may benefit from dual
therapy
However,…
– True utilization may depend upon real life clinical
experience with triple therapy and retrospective
analysis of IL28B
Ten years too late????