Impact of Pre-existing Mental Health Disorders on Adherence and Sustained Virologic Response with an Interferon-Free Trial of Sofosbuvir and Ribavirin for Chronic Hepatitis C
Amy Nelson1, Yu-Jin Lee1, Laura Heytens4, Susan Wroblewski3, William T Symonds5, John G. McHutchison5, Shyam Kottilil1, Anu Osinusi1,2
1LIR, NIAID / NIH, Bethesda, MD; 2SAIC-Frederick, Inc., Frederick, MD; 3Clinical Center Nursing, NIH, Bethesda, MMD; 4CCMD, NIH, Bethesda, MD; 5Gilead Sciences, Foster City, CA
Purpose: Mental health disorders (MHD) have long remained a barrier to treatment for those with chronic hepatitis C (HCV) infections. The complexity and side effect profile of interferon based HCV therapy make many patients with MHD ineligible, or unwilling to be treated. Our objective was to determine the impact of baseline MHD on adherence during an interferon-free study with a treatment regimen of sofosbuvir in combination with ribavirin. Methods: Sixty chronic HCV genotype-1, treatment naīve participants were treated with the NS5B RNA polymerase inhibitor sofosbuvir with either weight based or low dose ribavirin for 24 weeks. We identified all participants with significant baseline MHD defined as major depression, bipolar disorder, schizophrenia, generalized anxiety, and depression with anxiety or those requiring anti-depressants, antipsychotics, mood stabilizers or psychotropics. Participant adherence to required study visits (up to 24) was reviewed through treatment and follow up to date. Sofosbuvir adherence was documented during 11 time points based on participant recall and pill counts. Missed doses were recorded only through the time of treatment discontinuation in the six participants who stopped treatment early. Results: Of 60 participants, 23 met the criteria for significant baseline MHD. The prevalence of disorders was as follows: depression (18%), bipolar disorder (8%), depression with anxiety (5%), anxiety (3%), and schizophrenia (2%). There were no significant differences in completion of total required visits (97% vs. 98%) or study visits completed within required timeframes (95% vs. 95%) between participants in each group. Similar percentages had 3 or fewer total missed doses of the 168 doses of study medication in the MHD group vs. no MHD (84% vs. 83%). 〇f the six participants who stopped treatment early, 5 were in the baseline MHD group (83%). Reasons for early discontinuation were needle anxiety, renewed substance abuse post injury, poor adherence and lost to follow up. The overall sustained virologic response rate (SVR24) was 57% in those with baseline MHD vs. 65% in those without (p = 0. 59). In the 54 total participants that completed treatment, SVR24 was similar between groups; 7% in the MHD group vs. 64% in those without respectively (p = 0. 76). Conclusions: Our study suggests that while baseline MHD may contribute to early treatment discontinuations in all-oral interferon-free HCV treatments, these participants are appear similarly capable of completing a 24-week interferon-free regimen and achieving modest to high SVR rates.
William T. Symonds - Employment: Gilead
John G. McHutchison - Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences
The following people have nothing to disclose: Amy Nelson, Yu-Jin Lee, Laura Heytens, Susan Wroblewski, Shyam Kottilil, Anu Osinusi