Abstract. Background. Aim. Patients and Methods. Patients. Study Design

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Impct of the Use of Drugs nd Substitution Tretments on the Antivirl Tretment of Chronic Heptitis C: Anlysis of Complince, Virologicl Response nd Qulity of Life (CHEOBS). Melin, 1 J.-. Lng, D.

1 Impct of the Use of Drugs nd Substitution Tretments on the Antivirl Tretment of Chronic Heptitis C: Anlysis of Complince, Virologicl Response nd Qulity of Life (CHEOBS). Melin, 1 J.-. Lng, D. Ouzn, 3 M. Choustermn, M. Vrstet, 5 M. Rotily, 5 T. Fontnges, 6. Mrcellin, 7. Ccoub 8 1 Hôpitl Générl, Sint Dizier, Frnce; Centre Hospitlier Erstein, Erstein, Frnce; 3 Institut Arnud Tznck, Sint Lurent du Vr, Frnce; Hôpitl de Créteil, Créteil, Frnce; 5 ClinSerch, Bgneux, Frnce; 6 Centre de l Appreil Digestif, Bourgoin Jllieu, Frnce; 7 Hôpitl Beujon, Clichy, Frnce; 8 Hôpitl itié-slpêtrière, ris, Frnce Abstrct Bckground nd ims: CHEOBS is French multicenter, prospective, observtionl study tht imed to nlyse the fctors ssocited with dherence to tretment with peginterferon lfb nd ribvirin in chronic heptitis C ptients. The present nlysis focuses on dherence to ntivirl dul therpy, virologicl response, nd qulity of life (QoL) ccording to whether the ptients were ctive drug users or under substitution tretment (), ex-drug users (), or non-drug users (). tients nd methods: Between 3 nd 6, 18 clinicins evluted 1 heptitis C ptients every 3 months during tretment nd 6 months fter the end of tretment. Among these ptients, 11 were excluded from the nlysis. The studied popultion included, 578 nd 138. Good dherence ws defined by >8% of the dose nd durtion of the ntivirl dul therpy prescribed. Sustined virologicl response (SVR) ws defined by negtive CR 1 weeks fter the end of tretment. QoL ws ssessed using the SF-36 questionnire. Results: The ptient profile in the group ws between tht in the nd groups for men ge, body mss index (BMI), liver fibrosis, level of eduction or debt difficult to mnge, high consumption of lcohol, psychitric disorders, or chronic diseses. The proportion of good dherents to dul therpy ws similr in ll three groups:, 9.%;, %;, 5.% (p=.7). The SVR rte ws lso similr: 9.3%, 5.9%, nd 57.8%, respectively (p=.1). The QoL in the group ws less ltered on the physicl nd mentl levels thn in the other groups. Conclusions: The rte of SVR ws similr in the three groups. Excess consumption of lcohol, precrious socioeconomic sitution, nd the psychitric disorders observed in drug users in this study hd no negtive impct on the tretment outcomes. On the contrry, young ge, recent contmintion, high prevlence of genotype 3 infection, lower BMI, less severe liver fibrosis, nd good dherence to tretment seem to hve blnced the negtive prmeters. Bckground The French Consensus Conference of Februry recommended treting ptients infected with heptitis C virus (HCV) with stble drug use 1 Key findings from the Hepcom Study, 1-month, multicenter, observtionl prospective study of tretment-nive chronic heptitis C ptients treted in the French helth cre system, were : Only one-third of ptients with ccess to helth cre initited ntivirl tretment Access to tretment ws more difficult mong these ptient popultions: Women HIV-coinfected ptients Drug users receiving substitution therpy Dt from Hepcom reveled tht helth cre ccess ws still limited for drug users, suggesting tht further study of this ptient popultion ws needed Aim This nlysis from the CHEOBS study compred the efficcy, tolerbility, complince, nd effect on qulity of life of pegylted interferon (EG-IFN) lfb (egintron ; Schering-lough) + ribvirin (RBV) in 3 groups of ptients with chronic heptitis C Non-drug users () Ex-drug users () Active drug users or users undergoing substitution tretment () tients nd Methods tients tients ged 18 nd older who hd chronic heptitis C nd initited tretment with EG-IFN lfb (1.5 µg/kg/wk) lone or in combintion with RBV (8-1 mg/d, depending on body weight) were eligible for enrollment tients were tretment nive or were nonresponders or relpsers to previous nti-hcv therpy Study Design The CHEOBS study ws prospective, multicenter, observtionl study conducted between 3 nd 6 tients were enrolled from 18 centers in Frnce tht specilize in the mngement of heptitis C Questionnires Both the investigtor nd the ptient completed questionnires t bseline, pproximtely every 3 months during tretment, nd 6 months fter tretment cesstion The investigtor questionnire collected the following informtion: tient sociodemogrphic dt Therpeutic eduction provided to the ptient History of HCV infection lnned heptitis C tretment History of psychoctive drug use Tretment modifictions Heptitis C therpy received before inclusion Virologic sttus of the ptient 6 months fter in the CHEOBS study tretment cesstion tient self-questionnires collected the following informtion: Qulity-of-life ssessment (SF-36 form) Complince with EG-IFN lfb + RBV tretment Results This nlysis includes 1 ptients who were clssified s,, nd (including ptients undergoing substitution therpy) (Figure 1) Of the, 7 ptients were receiving methdone therpy nd 137 were receiving buprenorphine substitution tretment Figure 1. tient flow digrm. HCV = heptitis C virus. Non-drug users n = 138 tients with chronic HCV infection N = 1 Anlyzed n = 1 Ex-drug users tient sociodemogrphics, comorbidities, nd risk fctors re shown in Tble 1 Heptitis C disese chrcteristics for enrolled ptients re shown in Tble Tble 1. Bseline Chrcteristics of tients Excluded: n = 11 - Monotherpy (n = 37) - Dte of cesstion of combintion therpy unknown (n = 79) - Virologic response unknown (n = 5) Active drug users or substituted ptients n = 138 Sociodemogrphics n/n (%) n/n (%) n/n (%) Men 51/135 (9) 8/578 (7) 198/3 (8) <.1 Age, y, men ± SD 51.7 ± ± ± 6. <.1 BMI, kg/m, men ± SD 5.3 ± ±. 3. ± 3.7 <.1 Employment sttus <.1 rofessionl ctivity 5/135 (56) 385/578 (67) 138/ (57) Unemployed 7/135 (7) 11/578 () 88/ (36) Other 39/135 (38) 79/578 (1) 18/ (7) Eduction level <.1 Low 57/13 (56) 337/569 (59) 18/ () High 53/13 () 3/569 (1) 6/ (5) Indebtedness <.1 Difficult to mnge 3/83 () /71 (9) 8/6 (1) None or esy to mnge 8/83 (96) 9/71 (91) 178/6 () Comorbidities sychitric history Depression 183/136 (18) 1/578 (3) 95/ (39) <.1 Suicide ttempt 31/13 (3) 8/577 (8) 5/1 (19) <.1 Hospitliztion for mentl illness 6/131 (5) 63/5 (11) 7/ (19) <.1 sychitric illnesses 168/13 (16) 138/576 () 97/ () <.1 Other chronic illnesses 366/1 (36) 95/571 (17) 3/39 (13) <.1 Risk fctors Alcohol consumption, > g/d 3/169 (1) /187 () 3/93 (37) <.1 Tobcco consumption 18/11 (1) /569 () 17/ (9) <.1 = ctive drug user or user undergoing substitution tretment; BMI = body mss index; = ex-drug user; = non-drug user. Tble. Heptitis C Disese Chrcteristics nd Etiology n = 138 Source of HCV infection n/n (%) n/n (%) n/n (%) Trnsfusion 7/119 (7) 19/578 (3) 3/ (1) <.1 Drug buse 1/119 (1) 56/578 (95) 3/ (96) <.1 Other 5/119 (53) 8/578 (5) 9/ () <.1 Durtion of HCV infection, y, men ± SD 3.5 ± ± ± 7. <.1 Serum HCV RNA.1 8, IU/mL /77 (57) /3 (56) 116/18 (6) >8, IU/mL 33/77 (3) 19/3 () 66/18 (36) HIV coinfection 1/13 (1) 38/578 (7) 15/ (6).1 HBV coinfection 6/15 (1) 1/5 () 8/1 (3).3 METAVIR ctivity grde or equivlent. A or A1 8/891 (6) 1/89 (9) 7/19 (39) A or A3 83/891 (5) 8/89 (51) 118/19 (6) METAVIR fibrosis stge or equivlent.5 F or F1 31/895 (3) 17/9 (35) 7/193 (38) F or F3 39/895 (9) 5/9 (51) 13/193 (53) F 155/895 (17) 68/9 (1) 16/193 (8) = ctive drug user or user undergoing substitution tretment; = ex-drug user; HBV = heptitis B virus; HCV = heptitis C virus; HIV = humn immunodeficiency virus; = non-drug user. Or equivlent. The distribution of genotypes ws significntly different cross the 3 ptient groups (.1; Figure ) The proportions of ptients with genotype 3 infection were higher mong nd thn mong Among, most ptients hd genotype 1 or infection Figure. Distribution of genotypes Genotype 1 Genotype Genotype 3 Genotypes, 5, 6 Tretment Dosing, Durtion, nd Adherence There ws significnt heterogeneity cross the ptient groups in terms of durtion of tretment nd dosing of EG-IFN lfb (.1; Tble 3) Men durtion of therpy ws longer in thn in or Men EG-IFN lfb doses were higher in thn in or 9.9 Tble 3. Investigtor-Reported Dose nd Durtion n = 138 Men durtion of tretment, wk 37. ± ± ± 16.6 <.1 Erly discontinution 315/138 (3) 169/578 (9) 79/ (3).653 Therpeutic eduction 6/138 (58) 35/578 (56) 16/ (66).1 Men cumultive dosge EG-IFN lfb, µg/kg/wk 1.3 ± ±.7 1. ±.1.1 Ribvirin, mg/d 89 ± ± ± Men dosge t lst tretment EG-IFN lfb, µg/kg/wk 1.3 ± ±.3 1. ±.3 <.1 Ribvirin, mg/d 879 ± 897 ± ± Vlues re men ± SD or n/n (%). = ctive drug user or user undergoing substitution tretment; = ex-drug user; = non-drug user. < weeks genotype 1 (G1), G, G5, nd G6 infection; < weeks for G nd G3 infection. Adherence (>8% of the recommended dose of EG-IFN lfb nd RBV for >8% of the recommended durtion [ccording to genotype]) to therpy ws similr in ll ptient groups (Figure 3) Figure 3. Adherence to EG-IFN lfb + ribvirin therpy. 1 5 =.598 =. =.7 = Virologic Response Virologic response rtes ssessed t lest 1 weeks fter completion of therpy were not significntly different mong ptient groups (Figure ) Figure. Virologic response rtes t lest 1 weeks fter end of tretment Qulity of Life = Sustined virologic response = Nonresponse 8.3 Chnges in qulity-of-life scores throughout tretment re shown in Figure 5 Figure 5. Qulity of life (SF-36 form): mentl (top) nd physicl (bottom) composite scores. Men Chnge From Bseline Men Chnge From Bseline =.13 =.9 =.16 = Relpse = Month 3 Month 6 Month 1 osttretment =.7 =.9 = = Month 3 Month 6 Month 1 osttretment The incidence of dverse events is shown in Figure 6 Mentl dverse events were more common mong t month 3 nd month 1 thn mong nd Figure 6. All dverse events (top) nd ll mentl dverse events (bottom) =.16 =.91 =.1 = Mentl =. =.89 =.7 = Summry In this study, there ws predominnce of genotype 3 infection mong nd Adherence to therpy nd virologic response rtes were similr in,, nd Mentl dverse events were more frequent mong ; however, combintion therpy hd less negtive impct on qulity of life in these ptients thn in or Conclusions In this nlysis, ctive drug use ws frequently ssocited with excessive lcohol intke, vulnerble socioeconomic sitution, nd psychitric illness However, ctive drug use did not hve negtive impct on Adherence to EG-IFN lfb + RBV combintion therpy Rte of premture discontinution Sustined virologic response rte It is possible tht predominnce of fvorble chrcteristics, such s young ge, recent HCV infection, high prevlence of genotype 3 infection, low body mss index, nd less dvnced stge of fibrosis counterblnced the potentilly negtive impct of the unfvorble prmeters ssocited with ctive drug use References 1. Consensus Conference: Tretment of Heptitis C; Februry 78, ; ris, Frnce. Accessed October 6, 8.. Agostini H et l. Gstroenterol Clin Biol. 7;31: Disclosures. Melin, J.-. Lng, D. Ouzn, M. Choustermn, M. Rotily, T. Fontnges,. Mrcellin, nd. Ccoub re consultnts for Schering-lough Frnce. M. Vrstet hs nothing to disclose. 56. resented t the th Annul Meeting of the Europen Assocition for the Study of the Liver, April 6, 9, Copenhgen, Denmrk

2 Impct of the resented Chronic Heptitis 1 Hôpitl Générl, S Abstrct Bckground nd ims: CHEOBS is French multicenter, prospective, observtionl study tht imed to nlyse the fctors ssocited with dherence to tretment with peginterferon lfb nd ribvirin in chronic heptitis C ptients. The present nlysis focuses on dherence to ntivirl dul therpy, virologicl response, nd qulity of life (QoL) ccording to whether the ptients were ctive drug users or under substitution tretment (), ex-drug users (), or non-drug users (). tients nd methods: Between 3 nd 6, 18 clinicins evluted 1 heptitis C ptients every 3 months during tretment nd 6 months fter the end of tretment. Among these ptients, 11 were excluded from the nlysis. The studied popultion included, 578 nd 138. Good dherence ws defined by >8% of the dose nd durtion of the ntivirl dul therpy prescribed. Sustined virologicl response (SVR) ws defined by negtive CR 1 weeks fter the end of tretment. QoL ws ssessed using the SF-36 questionnire. Results: The ptient profile in the group ws between tht in the nd groups for men ge, body mss index (BMI), liver fibrosis, level of eduction or debt difficult to mnge, high consumption of lcohol, psychitric disorders, or chronic diseses. The proportion of good dherents to dul therpy ws similr in ll three groups:, 9.%;, %;, 5.% (p=.7). The SVR rte ws lso similr: 9.3%, 5.9%, nd 57.8%, respectively (p=.1). The QoL in the group ws less ltered on the physicl nd mentl levels thn in the other groups. Conclusions: The rte of SVR ws similr in the three groups. Excess consumption of lcohol, precrious socioeconomic sitution, nd the psychitric disorders observed in drug users in this study hd no negtive impct on the tretment outcomes. On the contrry, young ge, recent contmintion, high prevlence of genotype 3 infection, lower BMI, less severe liver fibrosis, nd good dherence to tretment seem to hve blnced the negtive prmeters. Bckground The French Consensus Conference of Februry recommended treting ptients infected with heptitis C virus (HCV) with stble drug use 1 Key findings from the Hepcom Study, 1-month, multicenter, observtionl prospective study of tretment-nive chronic heptitis C ptients treted in the French helth cre system, were : Only one-third of ptients with ccess to helth cre initited ntivirl tretment Access to tretment ws more difficult mong these ptient popultions: Women HIV-coinfected ptients Drug users receiving substitution therpy Dt from Hepcom reveled tht helth cre ccess ws still limited for drug users, suggesting tht further study of this ptient popultion ws needed Aim This nlysis from the CHEOBS study compred the efficcy, tolerbility, complince, nd effect on qulity of life of pegylted interferon (EG-IFN) lfb (egintron ; Schering-lough) + ribvirin (RBV) in 3 groups of ptients with chronic heptitis C Non-drug users () Ex-drug users () Active drug users or users undergoing substitution tretment () tients nd Methods tients tients ged 18 nd older who hd chronic heptitis C nd initited tretment with EG-IFN lfb (1.5 µg/kg/wk) lone or in combintion with RBV (8-1 mg/d, depending on body weight) were eligible for enrollment tients were tretment nive or were nonresponders or relpsers to previous nti-hcv therpy Study Design The CHEOBS study ws prospective, multicenter, observtionl study conducted between 3 nd 6 tients were enrolled from 18 centers in Frnce tht specilize in the mngement of heptitis C

3 e Use of Drugs nd S C: Anlysis of Compl. Melin, 1 J.-. Lng, D. Ouzn Sint Dizier, Frnce; Centre Hospitlier Erstein, Erstein, F 6 Centre de l Appreil Digestif, Bourgoi Questionnires Both the investigtor nd the ptient completed questionnires t bseline, pproximtely every 3 months during tretment, nd 6 months fter tretment cesstion The investigtor questionnire collected the following informtion: tient sociodemogrphic dt Therpeutic eduction provided to the ptient History of HCV infection lnned heptitis C tretment History of psychoctive drug use Tretment modifictions Heptitis C therpy received before inclusion Virologic sttus of the ptient 6 months fter in the CHEOBS study tretment cesstion tient self-questionnires collected the following informtion: Qulity-of-life ssessment (SF-36 form) Complince with EG-IFN lfb + RBV tretment Results. This nlysis includes 1 ptients who were clssified s,, nd (including ptients undergoing substitution therpy) (Figure 1) Of the, 7 ptients were receiving methdone therpy nd 137 were receiving buprenorphine substitution tretment Figure 1. tient flow digrm. HCV = heptitis C virus. s e Non-drug users n = 138 tients with chronic HCV infection N = 1 Anlyzed n = 1 Ex-drug users Excluded: n = 11 - Monotherpy (n = 37) - Dte of cesstion of combintion therpy unknown (n = 79) - Virologic response unknown (n = 5) Active drug users or substituted ptients tient sociodemogrphics, comorbidities, nd risk fctors re shown in Tble 1 Heptitis C disese chrcteristics for enrolled ptients re shown in Tble ) Tble 1. Bseline Chrcteristics of tients n = 138 Sociodemogrphics n/n (%) n/n (%) n/n (%) Men 51/135 (9) 8/578 (7) 198/3 (8) <.1 Age, y, men ± SD 51.7 ± ± ± 6. <.1 BMI, kg/m, men ± SD 5.3 ± ±. 3. ± 3.7 <.1 Employment sttus <.1 rofessionl ctivity 5/135 (56) 385/578 (67) 138/ (57) Unemployed 7/135 (7) 11/578 () 88/ (36) Other 39/135 (38) 79/578 (1) 18/ (7) Eduction level <.1 Low 57/13 (56) 337/569 (59) 18/ () High 53/13 () 3/569 (1) 6/ (5) Indebtedness <.1 Difficult to mnge 3/83 () /71 (9) 8/6 (1) None or esy to mnge 8/83 (96) 9/71 (91) 178/6 () Comorbidities sychitric history Depression 183/136 (18) 1/578 (3) 95/ (39) <.1 Suicide ttempt 31/13 (3) 8/577 (8) 5/1 (19) <.1 Hospitliztion for mentl illness 6/131 (5) 63/5 (11) 7/ (19) <.1 sychitric illnesses 168/13 (16) 138/576 () 97/ () <.1 Other chronic illnesses 366/1 (36) 95/571 (17) 3/39 (13) <.1 Risk fctors Alcohol consumption, > g/d 3/169 (1) /187 () 3/93 (37) <.1 Tobcco consumption 18/11 (1) /569 () 17/ (9) <.1 = ctive drug user or user undergoing substitution tretment; BMI = body mss index; = ex-drug user; = non-drug user. ed t the th Annul Meeting of the Euro

4 ubstitution Tretmen lince, Virologicl Re, 3 M. Choustermn, M. Vrstet, 5 M. Rotily, 5 T. Fontnge Frnce; 3 Institut Arnud Tznck, Sint Lurent du Vr, Fr in Jllieu, Frnce; 7 Hôpitl Beujon, Clichy, Frnce; 8 Hôp Tble. Heptitis C Disese Chrcteristics nd Etiology n = 138 Source of HCV infection n/n (%) n/n (%) n/n (%) Trnsfusion 7/119 (7) 19/578 (3) 3/ (1) <.1 Drug buse 1/119 (1) 56/578 (95) 3/ (96) <.1 Other 5/119 (53) 8/578 (5) 9/ () <.1 Durtion of HCV infection, y, men ± SD 3.5 ± ± ± 7. <.1 Serum HCV RNA.1 8, IU/mL /77 (57) /3 (56) 116/18 (6) >8, IU/mL 33/77 (3) 19/3 () 66/18 (36) HIV coinfection 1/13 (1) 38/578 (7) 15/ (6).1 HBV coinfection 6/15 (1) 1/5 () 8/1 (3).3 METAVIR ctivity grde or equivlent. A or A1 8/891 (6) 1/89 (9) 7/19 (39) A or A3 83/891 (5) 8/89 (51) 118/19 (6) METAVIR fibrosis stge or equivlent.5 F or F1 31/895 (3) 17/9 (35) 7/193 (38) F or F3 39/895 (9) 5/9 (51) 13/193 (53) F 155/895 (17) 68/9 (1) 16/193 (8) = ctive drug user or user undergoing substitution tretment; = ex-drug user; HBV = heptitis B virus; HCV = heptitis C virus; HIV = humn immunodeficiency virus; = non-drug user. Or equivlent. The distribution of genotypes ws significntly different cross the 3 ptient groups (.1; Figure ) The proportions of ptients with genotype 3 infection were higher mong nd thn mong Among, most ptients hd genotype 1 or infection Figure. Distribution of genotypes Genotype 1 Genotype Genotype 3 Genotypes, 5, 6 Tretment Dosing, Durtion, nd Adherence There ws significnt heterogeneity cross the ptient groups in terms of durtion of tretment nd dosing of EG-IFN lfb (.1; Tble 3) Men durtion of therpy ws longer in thn in or Men EG-IFN lfb doses were higher in thn in or open Assocition for the Study of the L

5 ts on the Antivirl Tre sponse nd Qulity o s, 6. Mrcellin, 7. Ccoub 8 nce; Hôpitl de Créteil, Créteil, Frnce; 5 ClinSerch, B itl itié-slpêtrière, ris, Frnce Tble 3. Investigtor-Reported Dose nd Durtion n = 138 Men durtion of tretment, wk 37. ± ± ± 16.6 <.1 Erly discontinution 315/138 (3) 169/578 (9) 79/ (3).653 Therpeutic eduction 6/138 (58) 35/578 (56) 16/ (66).1 Men cumultive dosge EG-IFN lfb, µg/kg/wk 1.3 ± ±.7 1. ±.1.1 Ribvirin, mg/d 89 ± ± ± Men dosge t lst tretment EG-IFN lfb, µg/kg/wk 1.3 ± ±.3 1. ±.3 <.1 Ribvirin, mg/d 879 ± 897 ± ± Vlues re men ± SD or n/n (%). = ctive drug user or user undergoing substitution tretment; = ex-drug user; = non-drug user. < weeks genotype 1 (G1), G, G5, nd G6 infection; < weeks for G nd G3 infection. Adherence (>8% of the recommended dose of EG-IFN lfb nd RBV for >8% of the recommended durtion [ccording to genotype]) to therpy ws similr in ll ptient groups (Figure 3) Figure 3. Adherence to EG-IFN lfb + ribvirin therpy. 1 =.598 =. =.7 = Virologic Response Virologic response rtes ssessed t lest 1 weeks fter completion of therpy were not significntly different mong ptient groups (Figure ) Figure. Virologic response rtes t lest 1 weeks fter end of tretment = = = Sustined virologic response Nonresponse Relpse Qulity of Life Chnges in qulity-of-life scores throughout tretment re shown in Figure 5 Figure 5. Qulity of life (SF-36 form): mentl (top) nd physicl (bottom) composite scores. Men Chnge From Bseline Men Chnge From Bseline =.13 =.9 = = Month 3 Month 6 Month 1 osttretment =.7 =.9 = = Month 3 Month 6 Month 1 osttretment iver, April 6, 9, Copenhgen, De

6 etment of f Life (CHEOBS) gneux, Frnce; The incidence of dverse events is shown in Figure 6 Mentl dverse events were more common mong t month 3 nd month 1 thn mong nd Figure 6. All dverse events (top) nd ll mentl dverse events (bottom). 1 =.16 =.91 =.1 = Mentl =. =.89 =.7 = Summry In this study, there ws predominnce of genotype 3 infection mong nd Adherence to therpy nd virologic response rtes were similr in,, nd Mentl dverse events were more frequent mong ; however, combintion therpy hd less negtive impct on qulity of life in these ptients thn in or Conclusions In this nlysis, ctive drug use ws frequently ssocited with excessive lcohol intke, vulnerble socioeconomic sitution, nd psychitric illness However, ctive drug use did not hve negtive impct on Adherence to EG-IFN lfb + RBV combintion therpy Rte of premture discontinution Sustined virologic response rte It is possible tht predominnce of fvorble chrcteristics, such s young ge, recent HCV infection, high prevlence of genotype 3 infection, low body mss index, nd less dvnced stge of fibrosis counterblnced the potentilly negtive impct of the unfvorble prmeters ssocited with ctive drug use References 1. Consensus Conference: Tretment of Heptitis C; Februry 78, ; ris, Frnce. Accessed October 6, 8.. Agostini H et l. Gstroenterol Clin Biol. 7;31: Disclosures. Melin, J.-. Lng, D. Ouzn, M. Choustermn, M. Rotily, T. Fontnges,. Mrcellin, nd. Ccoub re consultnts for Schering-lough Frnce. M. Vrstet hs nothing to disclose. enmrk

Efficacy of Pembrolizumab in Patients With Advanced Melanoma With Stable Brain Metastases at Baseline: A Pooled Retrospective Analysis

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