Table 2.
Ongoing studies of Boceprevir and Telaprevir with PEG-IFN and RBV in LT recipients with HCV genotype 1
| Study (ref) | Antiviral regimen | Immunosuppressant | % HCV-RNA undetectable | Immunosuppressant dose adjustments | % Adverse events |
|---|---|---|---|---|---|
| Coily (Ref #47) N=37 |
BOC 4 week PEG-IFN + RBV then BOC + PEG-IFN/RBV N=18 Mean Rx = 41 weeks TPV 4 week PEG-IFN + RBV; TPV + PEG-IFN + RBV × 12 week then PEG-IFN + RBV N=19 Mean Rx = 41 weeks |
BOC CSA =12 TAC =6 TPV CSA =10 TAC =9 |
BOC 56% Week 8 89% Week 16 72% Week 48 11% early viral breakthrough TPV 47% Week 8 58% Week 16 21% Week 48 21% early viral breakthrough |
BOC CSA 36% of original dose TAC 22% of original dose TPV CSA 54% of original dose TAC 5% of original dose All patients hospitalized for CNI dose adjustments |
BOC 100 % Anemia 61% Neutropenia 50% Thrombocytopenia 5% Rash 5% Nephrotoxicity 26% Infections 33% Hospitalization 11% DeathTPV 84% Anemia 21% Neutropenia 15% Thrombocytopenia 5% Rash 21% Nephrotoxicity 27% Infections 31% Hospitalization 5% Death |
| Pungpapong, (Ref #46) (n=60) |
BOC 4 week PEG-IFN + RBV then BOC + PEG-IFN/RBV (n=25) Mean Rx=39 wk TPV TPV + PEG-IFN/RBV × 12 wk then PEGIFN/RIB (n=35) Mean Rx = 32 wk |
BOC CSA = 23 TAC= 2 TPV CSA = 33 SRL =1 TAC =1 |
BOC 24% Week 8 40% Week 12 12% early viral breakthrough TPV 17% Week 4 80% Week 12 8% early viral breakthrough |
BOC CSA 33–100% (mean 56%) of original dosed every 12 hours TAC 86% reduction of original dose dosed twice weekly to every 48 hours TPV CSA 50–100% (mean 70%) of original dose every 12 hours SRL = 0.5 mg every 4 days TAC = 0.5 mg every 7 days |
BOC 100% Anemia 76% Leukopenia 36% increase SCr > 0.5 mg/dL 32% Rash 4 % Infections 4% Acute rejection 4% Death TPV 88% Anemia 77% Leukopenia 11% SCr increase > 0.5 mg/dL 31% Rash 6% Infections 6% Acute rejection 3% Death |
| Werner (Ref #49) (n=9) |
TPV TPV + PEG-IFN/RBV × 12 weeks then PEG-IFN/RBV Mean Rx= 12 wks |
TPV CSA = 4 TAC = 4 SRL = 1 |
TPV 44% Week 4 88% Week 12 |
TPV- Fold dose reduction TAC = 22 (96%) SRL = 7 (86%) CSA = 2.5 (60%) Immunosuppressant interval TAC – single dose per week SIRL – single dose per week CSA – single dose daily |
TPV 66% Anemia 66% Leukopenia 44% Thrombocytopenia 33% Rash 44% Hospitalized infection 11% Renal failure |
| Brown (Ref #48) (n=26) |
TPV TPV+PEG-IFN/RBV × 12 wks then PEG-IFN/RBV Mean Rx = 12 wks |
TPV TAC = 23 CSA =3 |
TPV 47% Week 4 82% Week 12 |
TPV CSA reduced 4-fold TAC reduced 10-fold Med time to 1st TAC dose =71 hrs Median TAC dose =0.5 mg every 7 days Med time to 1st CSA dose 22 hrs Med CSA dose =25 every 24 hrs |
TPV 39% Anemia 35% Rash (mild) 17% Anorectal symptoms 13% Pruritus 13% Renal insufficiency 4% Supratherapeutic CNI level (discontinued TPV) |
| O’Leary (Ref #44) (n= 120**) |
TPV/BOC TPV (n=107) or BOC (n=13) + PEG/IFN ± PEG-IFN/RBV lead-in (n=116) Median Rx = 148 days |
TPV/BOC TAC =35 CSA = 73 |
TPV/BOC 63% Week 4 78% Week 12 72% Week 24 7% Viral breakthrough |
TPV/BOC Median daily dose prior and after initiation of TPV or BOC CSA = 200 mg/50 mg TAC = 1.0 mg/0.19 mg |
TPV/BOC 79% Anemia 45% Blood transfusion 43% GCSF 20% Hospitalization 33% Scr increased > 0.5 mg/dL 6% Acute rejection 2% Death |
Abbreviations: BOC, boceprevir; CSA, cyclosporine; EVRL, everolimus; IS, immunosuppression; MMF, mycophenolate mofetil; PEG-IFN, peginterferon; RBV, ribavirin; Rx, treatment duration; Scr, serum creatinine; SIRL, sirolimus; TAC, tacrolimus; TPV, telaprevir
*
One patient received prolonged-release (once daily) tacrolimus
**
6 liver-kidney transplant recipients