Search

Susan Kearney,1,* Leslie J Raffini,2 Tan P Pham,3 Xin Ying Lee,4 Sylvia von Mackensen,5,* Andrea Landorph,6 Hideyuki Takedani,7 Johannes Oldenburg8 1Center for Bleeding and Clotting Disorders, Children’s Hospital Minnesota, Minneapolis, MN, USA; 2Division of Hematology, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; 3Mapi (an Icon plc company), Boston, MA, USA; 4Global Biopharm Patient Access, Biopharm Operations, Novo Nordisk A/S, Copenhagen, Denmark; 5Department of Medical Psychology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; 6Medical & Science, Biopharm Operations, Novo Nordisk A/S, Copenhagen, Denmark; 7Department of Joint Surgery, Research Hospital of the Institute of Medical Science, The University of Tokyo, Tokyo, Japan; 8Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany *These authors contributed equally to this work Background: Prophylactic treatment regimens lead to improvements in health-related quality-of-life (HRQoL) among individuals with hemophilia. Turoctocog alfa pegol (N8-GP) provides the benefit of extending the duration of protection from bleeding and reducing the number of injections, which is expected to impact HRQoL and treatment satisfaction (TS). Aim: To investigate the HRQoL and TS of patients with severe hemophilia A from two phase III trials evaluating the safety and efficacy of N8-GP. Methods: HRQoL was assessed using the Haemo-QoL (reported by children and their parents) and Haem-A-QoL (reported by adults). TS was assessed using Hemo-Sat. Domain and total scores for all questionnaires ranged from 0 to 100, with lower scores indicating a better HRQoL or TS. A negative change in score indicates an improvement in HRQoL/TS. Results: Mean changes in HRQoL scores were reported for 14 children aged 4–7 years, 21 children aged 8–11 years, 10 adolescents aged 13–16 years, and 163 adults (17 years and above). Mean changes in children/adolescents-reported Haemo-QoL total score were -14.0 for ages 4–7 years, -3.6 for ages 8–11 years, and -0.1 for ages 13–16 years. Mean changes in parent-reported Haemo-QoL total scores were -11.5 for 4–7 years, -8.6 for ages 8–11 years, and -4.0 for 13–16 years. Adults’ mean change in Haem-A-QoL total score was -3.1 for those receiving on-demand treatment and -2.3 for those receiving prophylaxis treatment. High levels of TS with N8-GP were reported by parents of children/adolescents and the adults at the end of the trial. Conclusion: While most patients reported a relatively good baseline HRQoL when entering the respective trials, the HRQoL of patients was either maintained or further improved when treated with N8-GP. Adults and parents of children and adolescents reported a high level of treatment satisfaction with N8-GP. Keywords: hemophilia A, turoctocog alfa pegol, health-related quality-of-life, children, adults, treatment satisfaction

Christian Beisland,1,2 Tom B Johannesen,3 Olbjorn Klepp,4 Ulrika Axcrona,5 Knut Martin Torgersen,6 Jan Kowalski,7 Oddvar Solli,6 Rickard Sandin,8 Jan Oldenburg9,10 1Department of Urology, Haukeland University Hospital, 2Department of Clinical Medicine, University of Bergen, Bergen, 3Department of Registration, Cancer Registry of Norway, Oslo, 4Department of Oncology, Ålesund Hospital, Ålesund, 5Department of Pathology, Oslo University Hospital, the Norwegian Radium Hospital, Oslo, 6Pfizer AS, Oslo, Norway; 7JK Biostatistics AB, Stockholm, 8Pfizer AB, Sollentuna, Sweden; 9Department of Oncology, Akershus University Hospital, Lørenskog, 10Medical Faculty, University of Oslo, Oslo, Norway Background: This population-wide retrospective, non-interventional registry study assessed changes in overall survival (OS) and factors influencing OS in Norwegian patients with renal cell carcinoma (RCC). Methods: Two population-wide health registries were used to identify all RCC patients with (mRCC) or without metastases diagnosed before (2002–2005) and after (2006–2008 and 2009–2011) introduction of targeted therapies. Median OS was estimated using Kaplan–Meier method. Cox proportional hazards regression modeling was used to identify prognostic factors. Results: Overall, 5,463 patients were diagnosed with RCC during 2002–2005 (n=1,898), 2006–2008 (n=1,631), and 2009–2011 (n=1,934); of these, 1,678 (31%) had mRCC. Patients diagnosed in 2009–2011 and 2006–2008 had significant (P

Abstract Objective HIV/HCV co-infection is characterised by accelerated progression of liver disease. Recently, the rsl2979860 C/T polymorphism in the IL28B gene has been linked to progression towards cirrhosis in HCV mono-infected patients and to treatment response of HCV-infection in HIV/HCV co-infected patients. Our aim was to clarify by non-invasive techniques if this polymorphism affects fibrosis progression in HIV/HCV co-infection. Methods In a cross-sectional design, liver stiffness (transient elastography), surrogate markers of liver fibrosis (APRI and FIB-4 scores) and rsl2979860 genotypes were analysed in 84 HCV/H1V co-infected patients. IL28B genotypes were determined by real-time PCR using a light cycler. In 56 HIV/HCV co-infected patients we also studied progression of fibrosis in relation to rsl2979860 C/T genotypes over two years. Results 82% of the patients were on HAART (74% without detectable HI viremia) and 67% were haemophiliacs, respectively. HCV genotype 1 was present in 62%. Cross-sectional median liver stiffness was 7.4 kPa and correlated with APRI and FIB-4 scores (r = 0.6 each, p < 0.001). Frequencies of IL28B genotypes were: CC 50%, CT 43% and TT 7%. In the cross-sectional analysis liver stiffness values were not different between the various IL28B-genotypes. Upon follow-up under HAART carriers of a C allele did not show further progression, while liver stiffness significantly increased in HIV/HCV co-infected patients with the T allele (p = 0.047). Conclusion Although progression of liver fibrosis was low under HAART in our cohort, progression was more pronounced in HIV/HCV genotype 1 co-infected patients with the T allele.

Abstract Objectives To estimate the cancer risk of HIV-infected patients in the HAART era with respect to a general reference population and to determine risk factors for malignancy. Methods Long term (1996-2009) cancer incidence of the Bonn single centre HIV cohort was compared to the incidence of the reference population of Saarland using standardized incidence ratios (SIR). Poisson regression analysis was used to identify predictors of cancer risk. Results 1,476 patients entered the cohort, enabling 8,772 person years of observation. 121 tumours in 114 patients, 7 in-situ and 114 invasive cancers, were identified. Malignancies associated with infectious agents such as Kaposi sarcoma (SIRs: male: 5,683; female: 277), non-Hodgkin lymphoma (SIRs male: 35; female: 18), anal cancer (SIRs male: 88; female: 115) as well a cervical carcinoma (SIR female: 4) and Hodgkin's disease (SIR male: 39) and liver cancer (SIR male: 18) were substantially more frequent in HIV-infected patients than in the general population (p < 0.001, each), whereas all other types of cancer were not increased. Poisson regression identified HAART (incidence rate ratio IRR (95% CI): 0.28 (0.19-0.41), p < 0.001), CD4 count (IRR per 100 cells/μl increase: 0.66 (0.57-0.76), p < 0.001), hepatitis B (IRR: 2.15 (1.10-4.20), p = 0.046) and age (IRR per 10 year increase: 1.23 (1.03 - 1.46), p = 0.023) as independent predictors for the occurrence of any type of cancer. Conclusions HAART and preserved CD4 cells preferentially reduce the risk of malignancies associated with oncogenic infections.

Abstract Objective Progressive immunodeficiency associated with HIV-infection leads to a progressive course of liver disease in HIV/HCV-co-infected patients. Highly active antiretroviral therapy (HAART) efficiently restores and preserves immune functions and has recently been demonstrated to also result in reduced liver-related mortality in HIV/HCV-co-infected patients. Methods To analyse differences in current liver fibrosis as a possible effect of HAART on fibrosis progression we assessed hepatic fibrosis by transient elastography in a cross-sectional comparison between HCV-mono-infected and HIV/HCV-co-infected patients presenting at our outpatient department in 2007. Results Overall, we did not find any difference in the distribution of liver stiffness between mono- (n = 84) and double-infected (n = 57) patients (14.4 kPa (10.8 - 18.2) versus 12.4 kPa (9.1 - 16.1), mean (95%-CI)). However, in the 8 HIV+ patients with CD4 counts < 200/μl liver stiffness was markedly greater (18.4 kPa (0.8 - 36.0)) than in HIV+ patients with preserved immunity (11.5 kPa (8.4 - 15.0)). Conclusions These findings are in line with other data that show an improved prognosis of chronic hepatitis C in HIV+ patients under effective HAART, and may be a hint that fibrosis progression in well-treated HIV+ patients will no longer be different from that in HCV-mono-infected patients.