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A Prospective, Multicenter, Observational Study on Adherence                                    With Viral Hepatitis C Tre...
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A Prospective, Multicenter, Observational Study on Adherence With Viral Hepatitis C Treatments (CHEOBS Study): Impact of Past Psychiatric Disorders on Sustained Virologic Response (SVR) EASL 2007

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A Prospective, Multicenter, Observational Study on Adherence With Viral Hepatitis C Treatments (CHEOBS Study): Impact of Past Psychiatric Disorders on Sustained Virologic Response (SVR) by JP Lang, P Melin, D Ouzan, L Cattan, M Chousterman, M. Rotily, T Fontanges, P Marcellin, P Cacoub

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A Prospective, Multicenter, Observational Study on Adherence With Viral Hepatitis C Treatments (CHEOBS Study): Impact of Past Psychiatric Disorders on Sustained Virologic Response (SVR) EASL 2007

  1. 1. A Prospective, Multicenter, Observational Study on Adherence With Viral Hepatitis C Treatments (CHEOBS Study): Impact of Past Psychiatric Disorders on Sustained Virologic Response (SVR) J. P. Lang,1 P. Melin,2 D. Ouzan,3 L. Cattan,4 M. Chousterman,5 J. M. Rotily,6 T. Fontanges,7 P. Marcellin,8 P. Cacoub9 1 Centre Hospitalier Erstein, Erstein, France; 2Hôpital Général, Saint Dizier, France; 3Institut Arnaud Tzanck, Saint Laurent du Var, France; 4Private Practice, Paris, France; 5Hôpital de Créteil, Créteil, France; 6 INSERM, Bagneux, France; 7Centre de l’Appareil Digestif, Bourgoin Jallieu, France; 8Hôpital Beaujon, Clichy, France; 9Hôpital Pitié-Salpêtrière, Paris, FranceAbstract Results Patient-Reported Adherence and Virologic Response • Adherence was similar at months 3 and 6 in PPD+ and PPD– patients (Figure 2).Background: The French multicenter, prospective, observational CHEOBS study was designed to • SVR rates were also similar between PPD+ and PPD– patients (Figure 3). Patient Dispositionevaluate adherence to peginterferon α-2b (PegIFN) plus ribavirin (RBV) combination in patients withchronic hepatitis C virus (HCV). • From January 2003 to December 2004, a total of 2000 patients with chronic hepatitis C were Figure 2. Patient-reported treatment adherence at 6 months (univariate analysis) included in the CHEOBS study (Figure 1).Aim: In this sub-analysis, we assessed the impact of past psychiatric disorders (PPDs) on treatment — 702 had G2/3 HCV infection; 641 were eligible for inclusion in this analysis. 100adherence and SVR in patients with genotype 2 or 3 (G2/3) infection. PPD+ ■ 61 received monotherapy or their treatment end date was unavailable. P = .59Methods: From Jan 2003 to Dec 2004, 702 out of 2000 patients included were infected with G2/3 virus, PPD–among which 641 had sufficient data to be analyzed: 460 patients without PPDs and 181 with PPDs. • Overall, 28% (181/641) of G2/3 patients had at least 1 PPD (depression, 93%; attempted suicide, 80PPDs were defined by depression (169, 93%) and/or attempted suicide (49, 27%) and/or psychiatric 27%; psychiatric hospitalization, 32%; Figure 1). P = .90 Adherent Patients, %hospitalization (58, 32%). Baseline characteristics, impact of PPD on adherence (=3 injections of PegIFN • Proportions of patients who were PPD+ (at least 1 PPD) or PPD– (no PPDs) and who were enrolled 76 P = .56 73during the past 4 weeks and =800 mg/d of RBV during the past week), and SVR (=21 weeks after in the therapeutic education program were similar between groups (61% vs 53%, respectively; P = .08). 60stopping therapy) were assessed. 61 62Results: At baseline, both groups did not differ significantly for most socio-demographic, virological, Figure 1. Patient disposition 54 51and histological characteristics. The rate of patients who received a therapeutic education was similar 40between PPD+ and PPD– patients (61% vs. 53%, p=0.08). Unemployment (30% vs. 12%, p=0.015),indebtedness (11% vs. 4%, p=0.005), lower study level (67% vs. 58%, p=0.025), former drug abuse PPD–(66% vs. 42%, p=0.001), current psychiatric disorders (64% vs. 8%, p=0.001), and the number of G3 72% 20(82% vs. 66%, p=0.001) were significantly more frequent in PPD+ patients. Current psychiatric disorders (n = 460) Patients G2/3 Patientswere depression (63%), anxiety (53%), chronic psychosis (6%), bipolar depression (3%), and others with HCV patients analyzed(2%). They were diagnosed by a psychiatrist in 71% of patients. The mean duration of treatment N = 2000 n = 702 0 n = 641(28.4 ± 12.3 vs. 29.4 ± 13.8 weeks, p=0.88), the rate of early discontinuations of treatment (13% PPD+ PEG-IFN alfa-2b RBV PEG-IFN alfa-2b +vs. 13%, p=0.89), the adherence to RBV plus PegIFN at month 6 (140/259, 54% vs. 54/107, 51%, 28% RBVp=0.56), and the SVR (88/101, 92% vs. 231/286, 83%, p=0.151) did not differ significantly between (n = 181) ExcludedPPD+ and PPD– patients, respectively. Excluded (monotherapy PEG-IFN = pegylated interferon; PPD = past psychiatric disorder; RBV = ribavirin. (not G2/3) or treatment endConclusion: In the real-life, for patients infected with genotype 2 or 3 treated with peginterferon n = 1298 date unavailable) Figure 3. Virologic response rates (univariate analysis)α-2b plus ribavirin, past psychiatric disorders were not a contraindication to HCV treatment, neither n = 61a risk of nonadherence nor nonsustained virological response. 100 P = .151 G = genotype; HCV = hepatitis C virus; PPD = past psychiatric disorder. PPD+Background Baseline Characteristics 80 92 PPD–• Adherence is an important component in treating patients with chronic hepatitis C with pegylated • Employment status, debt management, educational level, current psychiatric diagnosis, tobacco 83 interferon (PEG-IFN) plus ribavirin (RBV), particularly because these drugs are associated with consumption, and drug abuse profiles were significantly different between PPD+ and PPD– patients adverse effects. (Table 1). 60 Patients, %• Adherence is generally defined by the 80:80:80 rule, whereby at least 80% of the planned PEG-IFN • Proportions of patients with a history of injection or intranasal drug abuse, G3 HCV infection, or HIV alfa and 80% of the planned RBV doses are taken for at least 80% of the duration of the planned coinfection were significantly higher in the PPD+ group than in the PPD– group (Table 2). treatment.1 Table 1. Sociodemographic Baseline Characteristics 40• Clinical trial data indicate that adherence differentially affects response to therapy, depending Baseline Characteristic PPD+ PPD– P on hepatitis C virus (HCV) genotype. (n = 181) (n = 460) Men, n/N (%) 107/181 (59) 273/459 (59) .92 20 — For genotype 1 (G1) patients, adherence is closely related to treatment outcome, with higher sustained virologic response (SVR) rates reported in adherent patients.1 Mean age ± SD, y 42.9 ± 9.6 45.2 ± 12 .08 3 5 5 — For genotype 2 or 3 (G2/3) patients, SVR rates are similar among G2/3 patients who meet the Mean body mass index ± SD, kg/m2 23.7 ± 4.2 23.9 ± 4.2 .46 11 0 80:80:80 rule and among those who are less adherent.1,2 Employment status, n/N (%) <.001 Sustained Responders* Nonresponders Relapsers• The impact of adherence among G2/3 patients in real-world clinical practice is unknown, particularly Professional activity 95/181 (52) 296/459 (64) in those with comorbid or past psychiatric disorders (PPDs). PPD = past psychiatric disorder. Unemployed 54/181 (30) 56/459 (12) *Defined as those with undetectable serum HCV RNA 21 weeks or more after the end of treatment. Other 32/181 (18) 107/459 (23)Aim Educational level, n/N (%) .02 Treatment Dosing and Duration • Mean number of PEG-IFN alfa-2b injections and RBV capsules (in milligrams) was similar in the <High school 122/181 (67) 261/452(58)• To assess the impact of PPDs on treatment adherence and SVR rates among patients with chronic PPD+ and PPD– groups (Figure 4). hepatitis C infected with G2/3 HCV. ≥High school 59/181 (33) 191/452 (42) • Mean duration of PEG-IFN alfa-2b and RBV therapy was approximately 29 weeks in each group, as Origin of income, n/N (%) <.001 reported by the investigator (Table 3).Patients and Methods Employment Unemployment 73/178 (41) 44/178 (25) 258/455 (57) 55/455 (12) • Mean duration of HCV treatment, rate of early discontinuation, and dose of PEG-IFN alfa-2b and of RBV were similar in both groups (Table 3). Other 61/178 (34) 142/455 (31)Patients Figure 4. Patient-reported mean number of PEG-IFN alfa-2b injections administered and Indebtedness, n/N (%) .005 RBV capsules consumed at 6 months of treatment• Only patients with G2/3 HCV infection were included in this analysis. Difficult to manage 17/153 (11) 16/371 (4)• Included were patients 18 years or older with chronic hepatitis C who were treated with PEG-IFN alfa-2b (PegIntron®) (1.5 µg/kg/wk), alone or in combination with weight-based RBV (800 mg/d, None or easily managed 136/153 (89) 355/371 (96) P = .61 1000 mg/d, or 1200 mg/d, depending on body weight). Current psychiatric disorder, n/N (%) 115/181 (64) 35/453 (8) <.001 25 PPD+• Patients could be treatment naive or nonresponsive to or have relapsed after previous therapy. Depression 69/110 (63) 3/24 (13) 21.4 PPD–• PPD was indicated by a previous diagnosis of depression, a documented suicide attempt, a hospital Anxiety 58/110 (53) 22/24 (92) 20 20.9 stay because of a psychiatric condition, or any combination of these. Chronic psychosis 6/110 (5) —Study Design Bipolar depression 3/110 (3) — Mean Number 15• CHEOBS is a French, prospective, multicenter, observational study designed to evaluate adherence Other 2/110 (2) 1/24 (4) with PEG-IFN alfa-2b (1.5 µg/kg/wk) and weight-based RBV (800-1200 mg/d) combination therapy Chronic disease, n/N (%) 43/178 (24) 104/455 (23) .75 in patients with chronic hepatitis C in a real-world, community-based setting. Alcohol consumption >14 glasses/wk, n/N (%) 11/64(17) 21/100 (21) .687 10• 100 centers in France that specialize in the management of hepatitis C were invited to participate P = .77 Tobacco consumption, n/N (%) 136/181 (75) 200/451 (44) <.001 in the study. Drug abuse, n/N (%) <.001 5Questionnaires None 47/181 (26) 251/457 (55) 2.9 3.1• Some patients in the study participated in a therapeutic education program, defined as intervention Former 120/181 (66) 192/457 (42) by a third person (eg, nurse, behavioral specialist), during the first 3 months of therapy to optimize 0 Current 14/181 (8) 14/457 (3) tolerance to and efficacy of PEG-IFN alfa-2b and RBV. RBV Capsules* PEG-IFN alfa-2b Injections† PPD = past psychiatric disorder. PEG-IFN = pegylated interferon; PPD = past psychiatric disorder; RBV = ribavirin.• Every 3 months during treatment and 6 months after treatment cessation, investigator and patient *During the previous 7 days. questionnaires were completed. Table 2. Hepatitis C History †During the previous 4 weeks.• The investigator questionnaire collected information on the following: Baseline Characteristic PPD+ PPD– P — Patient sociodemographic data. (n = 181) (n = 460) Table 3. Investigator-Reported Treatment Doses and Duration — History of HCV infection. Source of HCV infection, n/N (%) PPD+ PPD– P — History of psychoactive drug consumption. Transfusion 28/181 (15) 103/460 (22) .051 (n = 181) (n = 460) Injection or intranasal drug abuse 129/181 (71) 201/460 (44) <.001 Mean duration ± SD, wk* 28.4 ± 12.3 29.4 ± 13.8 .88 — Hepatitis C therapy received before inclusion in the CHEOBS study. Other 25/181 (14 ) 156/460 (34) <.001 Early discontinuation (<20 wk), n/N (%) 24/181 (13) 59/460 (13) .89 — Therapeutic education provided to the patient. Mean duration of HCV infection ± SD, y 19.8 ± 7.5 20.1 ± 8.6 .84 PEG-IFN alfa-2b weekly dose, µg/kg† 1.4 ± 0.26 1.3 ± 0.3 .58 — Planned hepatitis C treatment. Serum HCV RNA, n/N (%) RBV daily dose, mg† 858 ± 159 870.6 ± 163.2 .30 — Treatment modifications during follow-up. PEG-IFN = pegylated interferon; PPD = past psychiatric disorder; RBV = ribavirin. ≥800,000 IU/mL 71/125 (57) 199/308 (65) .15 *Date of end of combination therapy minus date of study entry. — Virologic status of the patient 6 months after treatment cessation. † As reported by the investigator at the last visit under treatment. >800,000 IU/mL 54/125 (43) 109/308 (35)• The patient self-questionnaire collected information on the following: HCV genotype, n/N (%) <.001 — Nature and source of therapeutic education received for chronic hepatitis C and associated treatment. G2 32/181 (18) 157/460 (34) Conclusions G3 149/181 (82) 303/460 (66) — Responses to quality-of-life assessment (Short Form-36). • This is the first prospective, community-based study to evaluate treatment adherence among Coinfection, n/N (%) patients with G2/3 HCV infection. — Self-reported adherence to PEG-IFN alfa-2b and RBV treatment. HIV 13/181 (7) 14/458 (3) .028 • Patients with at least 1 PPD reported rates of adherence to treatment and attained sustainedAssessments Hepatitis B virus surface antigen positive 2/181 (1) 3/458 (1) .44 response rates similar to those of patients without previous psychiatric diagnoses.• Treatment adherence was assessed at month 3 and month 6 during treatment and was defined as METAVIR activity grade, n/N (%) .21 — The presence of 1 or more PPDs should, therefore, not be considered a contraindication to the patient having A0 or A1 59/131 (45) 176/342 (51) HCV treatment with PEG-IFN alfa-2b and RBV. — 3 to 4 injections of PEG-IFN alfa-2b during the past 4 weeks. A2 or A3 72/131 (55) 166/342 (49) — At least 800 mg/d of RBV during the past week. METAVIR fibrosis stage, n/N (%) .14• Virologic response was defined as — Nonresponse (detectable HCV RNA at the end of treatment). F0 or F1 51/131 (39) 156/342 (46) References F2 or F3 65/131 (50) 136/342 (40) — Sustained response (undetectable HCV RNA for at least 21 weeks after treatment cessation). 1. McHutchison JG, et al. Gastroenterology. 2002;123:1061-1069. F4 15/131 (11) 50/342 (15) — Relapse (undetectable HCV RNA at the end of treatment and detectable HCV RNA during the 2. Zeuzem S, et al. J Hepatol. 2004;40:993-999. Mean Knodell score ± SD 8.9 ± 3.6 7.8 ± 3.1 .034 6 months of follow-up). Previous anti–HCV treatment course, n/N (%) .262• Virologic status was determined by qualitative and quantitative polymerase chain reaction. None 142/181 (78) 378/459 (82)Statistical Analysis One or more 39/181 (22) 81/459 (18)• Group comparisons were performed with use of the Kruskal-Wallis test and logistic regression, HCV = hepatitis C virus; PPD = past psychiatric disorder. where α = 5% and β = 80%. Supported by Schering-Plough. Presented at the 42nd Annual Meeting of the European Association for the Study of the Liver; 11-15 April 2007; Barcelona, Spain

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