To the editor,
We read with great interest the research article, ‘‘Effectiveness of Telaprevir and Boceprevir Triple Therapy for Patients with Hepatitis C Virus in a Large Integrated Care Setting’’ by Price et al. [1]. To date, there have been few reports on treatment initiation and effectiveness of telaprevir- and boceprevir-based triple regimens in clinical practice. In this paper, only 6.8 % patients were started on therapy and overall 54 % achieved SVR. A disappointing 37 % of cirrhotics achieved SVR.
Previously, our group showed that 18.7 % of patients from two large academic centers in Dallas and Miami were initiated on treatment with triple therapy during the first 12 months following approval of boceprevir and telaprevir [2]. Here, we would like to share our results of patients treated with triple therapy beginning 6/1/2011 through 11/30/2012 from this Dallas–Miami cohort.
A total of 154 patients were treated (Dallas—48, Miami—106). Data were collected through 6/30/13 to allow 6 months of follow-up. Protease inhibitor was chosen at the discretion of the provider.
Baseline variables (Tables 1, 2) included site, age, white blood cells, hemoglobin, platelets, alanine aminotransferase, albumin, body mass index (BMI, categorized by normal/overweight/obese), viral load (VL < or ≥ 800,000 IU/L), specific protease inhibitor, presence of cirrhosis, and history of decompensation. The primary outcome was SVR at 12 or 24 weeks post-treatment. On-treatment measures included hospital admissions and need for blood transfusions.
Table 1.
Baseline and end-of-treatment variables meeting statistical significance or qualifying for multivariable analysis
| Variable | Population (n = 154) median (IQR) or n (% of total) |
SVR median (IQR) or n (% of variable) |
No. SVR median (IQR) or n (% of variable) |
Sig |
|---|---|---|---|---|
| Site | 0.11 | |||
| Dallas | 48 (31.2 %) | 21 (43.8 %) | 27 (56.3 %) | |
| Miami | 106 (68.8 %) | 61 (57.5 %) | 45 (42.5 %) | |
| Race | 0.0004 | |||
| White | 114 (74.0 %) | 68 (59.6 %) | 46 (40.4 %) | |
| AA/Black | 25 (16.2 %) | 4 (16.0 %) | 21 (84.0 %) | |
| Asian | 5 (3.2 %) | 4 (80.0 %) | 1 (20.0 %) | |
| Other | 4 (2.6 %) | 1 (25.0 %) | 3 (75.0 %) | |
| Unknown | 6 (3.9 %) | 5 (83.3 %) | 1 (16.7 %) | |
| Ethnicity | 0.0001 | |||
| Non-hispanic/non-latino | 105 (71.9 %) | 45 (42.9 %) | 60 (57.1 %) | |
| Hispanic/latino | 41 (28.1 %) | 32 (78.0 %) | 9 (22.0 %) | |
| ALT | 60 (7–402) | 46 (7–350) | 69 (14–402) | 0.0094 |
| Albumin | 4.2 (1.4–5) | 4.3 (1.4–5) | 4.1 (2–4.7) | 0.0001 |
| Cirrhosis | 72 (46.8 %) | 28 (38.9 %) | 44 (61.1 %) | 0.0008 |
| History of Decompensation | 15 (9.7 %) | 3 (20.0 %) | 12 (80.0 %) | 0.0066 |
| VL (≥ 800,000 IU/L) | 110 (73.8 %) | 52 (47.3 %) | 58 (52.3 %) | 0.0083 |
| Treatment history | 0.0004 | |||
| Naïve | 49 (31.8 %) | 32 (65.3 %) | 17 (34.7 %) | |
| Non-responder | 56 (36.4 %) | 18 (32.1 %) | 38 (67.9 %) | |
| Relapser | 49 (31.8 %) | 32 (65.3 %) | 17 (34.7 %) | |
| BMI category | 0.0313 | |||
| Normal < 25 | 51 (33.1 %) | 33 (64.7 %) | 18 (35.3 %) | |
| Overweight 25–<30 | 54 (35.1 %) | 30 (55.6 %) | 24 (44.4 %) | |
| Obese ≥ 30 | 49 (31.8 %) | 19 (38.8 %) | 30 (61.2 %) | |
| On-treatment and end-of-treatment variables | ||||
| pRBC infusion | 29 (18.8 %) | 10 (34.5 %) | 19 (65.5 %) | 0.0249 |
| Early discontinuation | 69 (44.8 %) | 11 (15.9 %) | 58 (84.1 %) | <0.0001 |
| Hospital admission during treatment | 43 (27.9 %) | 17 (39.5 %) | 26 (60.5 %) | 0.0338 |
| Discontinuation reason | <0.0001 | |||
| Completed therapy | 84 (54.5 %) | 72 (85.7 %) | 12 (14.3 %) | |
| Non-responder/futility | 18 (11.7 %) | 0 | 18 (100.0 %) | |
| Side effects | 33 (21.4 %) | 7 (21.2 %) | 26 (78.8 %) | |
| Heme side effects | 15 (9.7 %) | 3 (20.0 %) | 12 (80.0 %) | |
| Financial/death/other | 4 (2.6 %) | 0 | 4 (100.0 %) |
Chi-squared and Fisher’s exact test used when appropriate. Variables not meeting a significance criterion of ≤2.000 are available in Table 2
IQR interquartile range, SVR sustained viral response, Sig significance, AA African American, ALT alanine aminotransferase, VL viral load, IU/L international units/liter, BMI body mass index, pRBC packed red blood cells
Table 2.
Non-statistically significant baseline variables
| Variable | Population (n = 154) median (IQR) or n (%) |
SVR (n = 82) median (IQR) or n (%) |
No SVR (n = 72) median (IQR) or n (%) |
Sig |
|---|---|---|---|---|
| DAA | 0.54 | |||
| Boceprevir | 31 (20.1 %) | 15 (48.4 %) | 16 (51.6 %) | |
| Telaprevir | 123 (79.9 %) | 67 (54.5 %) | 56 (45.5 %) | |
| Male | 94 (61.0 %) | 51 (54.3 %) | 43 (45.7 %) | 0.75 |
| Age (years) | 57 (20–73) | 57 (20–73) | 57 (28–71) | 0.35 |
| White blood cells | 5.5 (0.3–36.7) | 5.4 (0.3–36.7) | 5.5 (1.7–9.8) | 0.95 |
| Hemoglobin | 14.6 (7.7–17.7) | 14.6 (9.8–17.7) | 14.4 (7.7–17.4) | 0.46 |
| Platelets | 155 (39.5–449) | 154 (39.5–343) | 158 (42.1–449) | 0.66 |
| HCV genotype | 0.51 | |||
| 1a | 83 (53.9 %) | 41 (49.4 %) | 42 (50.6 %) | |
| 1b | 52 (33.7 %) | 31 (59.6 %) | 21 (40.4 %) | |
| 1 Undetermined | 19 (12.3 %) | 10 (52.6 %) | 9 (47.4 %) |
None of the variables were included in the multivariable analysis
IQR interquartile range, SVR sustained viral response; Sig significance
Nearly 80 % of patients were treated with telaprevir and 20 % with boceprevir. In total, 53.2 % achieved SVR. SVR was particularly low in cirrhotic patients (38.9 %) versus non-cirrhotics (65.0 %). On multivariate analysis (Table 3), predictors of response included higher baseline albumin levels (OR 4.51, CI 1.76–11.5). Baseline VL ≥ 800,000 IU/mL (OR 0.30, CI 0.11–0.84), cirrhosis (OR 0.41, CI 0.17–0.95), and BMI ≥ 30.0 (OR 0.29, CI 0.10–0.81) were inversely associated with attaining SVR.
Table 3.
Multivariable logistic regression
| Variable | Odds ratio | 95 % CI | Sig |
|---|---|---|---|
| Cirrhosisa | 0.41 | 0.17–0.95 | 0.0388 |
| Age | 1.01 | 0.97–1.05 | 0.76 |
| Ethnicitya | 5.12 | 1.82–14.4 | 0.0019 |
| Alanine aminotransferase | 0.99 | 0.99–1.00 | 0.53 |
| Albumina | 4.51 | 1.76–11.5 | 0.0017 |
| Viral load ≥ 800,000 IU/La | 0.30 | 0.11–0.84 | 0.0210 |
| BMI ≥ 30a | 0.29 | 0.10–0.80 | 0.0172 |
| 25 ≥ BMI < 30 | 0.70 | 0.26–1.89 | 0.48 |
| Site | 1.34 | 0.53–3.34 | 0.54 |
Overall logistic regression analysis was significant at p < 0.0001
Sig significance, ALT alanine aminotransferase, IU/L international units/liter, BMI body mass index
Indicates continual significance after multivariable analysis
Despite considerable prior experience with first-generation directly acting antivirals, the overall SVR rate was lower than anticipated based on registration trials (a near 20 % drop in SVR [3]). Our data are consistent with the data presented in this paper [1] and also with the other published reports on SVR in clinical practice including the French Early Access Project (CUPIC)—which had cirrhotic SVR rates of 43 % (boceprevir) and 52 % (telaprevir) [4]; UCSF—which compared SVR rates in compensated (54 %) and mildly decompensated (35 %) cirrhotics [5]; and the national VA experience (SVR of 50 % for boceprevir and 52 % for telaprevir) [6].
It will be interesting to find out to what extent treatment initiation rates will rise with the use of second-generation directly acting antivirals available now and others nearing approval in the coming months. Our results are important to establish true SVR rates in clinical practice, specifically for patient profiles that were underrepresented in the registration trials. Also, these data will still be relevant in resource-poor regions of the world, which will continue to use boceprevir and telaprevir. Lastly, it is important to learn from our prior experiences, as often we face unexpected challenges in clinical practice.
Contributor Information
Perry H. Dubin, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA Doris Duke Foundation, New York, NY, USA.
Seth N. Sclair, Email: ssclair@med.miami.edu, Division of Hepatology, Department of Medicine, Center for Liver Diseases, University of Miami Miller School of Medicine, 1500 NW 12th Ave, Suite 1101, Miami, FL 33136, USA.
Rene Rico, Division of Hepatology, Department of Medicine, Center for Liver Diseases, University of Miami Miller School of Medicine, 1500 NW 12th Ave, Suite 1101, Miami, FL 33136, USA.
Amelia K. Boehme, Birmingham Department of Biostatistics and Epidemiology, University of Alabama, Tuscaloosa, AL, USA
Emerson Y. Chen, Division of Hepatology, Department of Medicine, Center for Liver Diseases, University of Miami Miller School of Medicine, 1500 NW 12th Ave, Suite 1101, Miami, FL 33136, USA
Paul Martin, Division of Hepatology, Department of Medicine, Center for Liver Diseases, University of Miami Miller School of Medicine, 1500 NW 12th Ave, Suite 1101, Miami, FL 33136, USA.
William M. Lee, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
References
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