Treatment Comparative Effectiveness In Rare Diseases: The Case of Transthyretin Familial Amyloid Polyneuropathy Survival

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steroids regimens after first-line therapy failure was 55.9%.  The most common second-line steroid regimen used was prednisolone alone.  Steroid side effects, including hyperglycemia, dizziness, dyspepsia, edema, flushing, malaise, and pruritus were reported in 21.7% of treated patients.  Conclusions: Corticosteroids remained as the mainstay of therapy for both first- and second-line management of primary ITP in Hong Kong with acceptable outcomes. Further studies may be warranted to investigate the risk and benefits of various steroid regimens and newer agents. PSY14 Matching Adjusted Indirect Comparison (MAIC) Analysis For Ponatinib Vs Bosutinib In Third-Line Chronic Phase Chronic Myeloid Leukemia (CP-CML) Iannazzo S1, McGarry L2, Lustgarten S2, Chiroli S3 1SIHS SRL, Torino, Italy, 2ARIAD Pharmaceuticals, Inc., Cambridge, MA, USA, 3INCYTE, Epalinges, Switzerland

Objectives: In cost-effectiveness analysis in oncology, relative effects of competing treatments are rarely available from head-to-head trials. For tyrosine kinase inhibitors ponatinib and bosutinib, indicated for third-line CP-CML, efficacy data are derived from single-arm trials, making unfeasible the application of traditional network meta-analysis approaches. Matching-adjusted indirect comparison (MAIC) is a novel method that can be used to overcome an incomplete evidence network.  Methods: An MAIC analysis was conducted to compare efficacy in the subgroup of third-line CP-CML patients in the ponatinib trial (PACE) and bosutinib trial (NCT00261846; published by Khoury 2012). Individual patients treated with ponatinib in the PACE study were assigned weights obtained from a logistic regression model for the propensity of being treated with bosutinib vs. ponatinib. The mean baseline characteristics in the reweighted PACE data were expected to closely match those reported for patients treated with bosutinib. The weights were used to produce matching-adjusted estimates of ponatinib best response rates, in terms of complete (CCyR) and partial (PCyR) cytogenetic response, complete hematologic response (CHR), and no response (NR).  Results: Baseline characteristics, including gender, race, median age, median time since diagnosis, ECOG performance status, and T315I mutation at study entry of the adjusted ponatinib cohort matched those of bosutinib. The effective sample size from PACE decreased from 97 to 69 patients, as a consequence of matching. Best response rates in the matched-adjusted ponatinib cohort (CCyR: 61.34%, PCyR: 8.46%, CHR: 18.19%, and NR: 12.01%) were consistent with unadjusted results (CCyR: 64.95%, PCyR: 6.19%, CHR: 17.53%, and NR: 11.34%), with considerably more ponatinib patients in deeper response categories versus bosutinib (CCyR: 24.07%, PCyR: 8.33%, CHR: 37.93%, and NR: 29.66%).  Conclusions: Adjusted ponatinib response rates in third-line CP-CML were similar to unadjusted outcomes, suggesting that the higher efficacy observed in ponatinib versus bosutinib trial is not due to cohort imbalances. PSY15 Levonorgestrel Intrauterine System And Norethisterone For The Treatment of Chronic Abnormal Uterine Bleeding: A Randomized Clinical Comparison In The Patients of Bahawalpur, Pakistan Ashraf MN1, Murtaza G2 of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Bahawalpur - 63100, Pakistan, Bahawalpur, Pakistan, 2Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan 1Faculty

Objectives: This study was aimed at the comparison of therapeutic outcome of Levonorgestrel Intrauterine System (LNG-IUS) and norethisterone in idiopathic chronic Abnormal Uterine Bleeding (AUB) in the patients of Bahawalpur, Punjab province, Pakistan.  Methods: This study was carried out for six months in the selected clinical settings of Bahawalpur. After recruiting the patients with AUB, they were equally divided into two groups, i.e. group A and B that were treated with LNGIUS and norethisterone, respectively. A predesigned questionnaire was employed to collect various information like mean age, duration of the disease and parity. Besides, the main outcomes of this treatment was reduction in menstrual blood loss (MBL) that was tested by the PBAC score. The PBAC score was recorded on day 1, 90th day, and 180th day after start of therapy.  Results: There was statistically non-significant (P >  0.05) difference in the mean age, mean duration of the disease, and the reduction in MBL of both groups after 3 months. After a treatment of 180 days, the reduction in MBL was significantly (P <  0.05) higher in group A (94.74%) than group B patients (73.68%). It shows good treatment response in group A than group B. However, the response of both the treatments showed no association with the patient’s age, parity and chronicity of the disease.  Conclusions: The local population of Bahawalpur, Pakistan suffering from idiopathic chronic AUB can efficiently be treated by using the LNG-IUS than norethisterone; since the former showed potential clinical benefits in terms of reduction in MBL. PSY16 Eficacy And Satefy of Methylprednisolone In The Treatment of Idiopathic Thrombocytopenic Purpura Rego MJ1, Araujo BC2, Galdino-Pitta MR2, Zanghelini F3, Nunes TR2, Landim MS3, Oliveira MD1, Pereira MC2, Viana DC4, Andrade CA1, Pitta MG1 1Universidade Federal de Pernambuco, Recife, Brazil, 2University Federal de Pernambuco, Recife, Brazil, 3UFPE, Recife, Brazil, 4Avenida Professor Moraes Rego, Recife, Brazil

Objectives: To evaluate the therapeutic indication of 40mg/m and 125mg/ml injectable suspension (IV) methylprednisolone in the treatment of people with idiopathic thrombocytopenic purpura.  Methods: A literature search was carried out on February 04, 2015 in the following databases: BMJ - Best Practice, Dynamed and UpToDate. It was chosen to use evidence synthesis databases due to the fact that it is a medical issue which daily brings new information on the subject and it enables to recover the original information examined, commented and evaluated critically, according to the methodology recommended by clinical epidemiology. The search strategy adopted the vocabulary of structured Descriptors in Health Sciences (DeCS)

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and Medical Subject Headings (MeSH) to better identify the references of interest. Indexed terms used in the research were: “Purpura, Thrombocytopenic, Idiopathic” and “Methylprednisolone.”  Results: According to the evidence located in BMJ the use of corticosteroids (methylprednisolone) is indicated as first-line treatment in patients with idiopathic thrombocytopenic purpura in some situations. According to the located in Dynamed, the use of high doses of methylprednisolone (oral 30 mg/kg/day for 3 days plus oral 20mg/kg/day for 4 days) is indicated as second-line therapy for the treatment of patients with persistent or chronic idiopathic thrombocytopenic purpura. Since the evidence synthesis found in UpToDate showed that for treatment of patients with serious bleeding and platelet count < 30,000/ microL it is recommended the immediate use of platelet transfusion, intravenous immunoglobulin or 1g intravenous methylprednisolonefor 3 days.  Conclusions: According to the presented syntheses, there is not enough evidence about the use of methylprednisolone in treating people with idiopathic thrombocytopenic purpura. Thus, we do not recommend the inclusion of 40mg/mL and 125mg/ml injectable suspension (IV) methylprednisolone in RENAME 2016, being maintained only the 500mg injectable lyophilized powder pharmaceutical form. PSY17 Indications For Prescription of Immodin®, Its Efficacy And Effect on The Most Commonly Examined Immunological Parameters Hrubisko M1, Keszegh J2, Hrubisko M3, Panakova I1, Marusakova E4 1IMUNA PHARM a.s., Sarisske Michalany, Slovakia, 2Kantar Health, Bratislava, Slovakia, 3OUSA, Bratislava, Slovakia, 4Medical Care Consulting Ltd., Lozorno, Slovak Republic

Objectives: Evaluation of the effectiveness of IMMODIN® by the assessment of documented recurrent infections comparing its incidence during the last year´s period preceding the treatment to the incidence during one year period following the start of the treatment. Summarization of the indications for the prescription in routine clinical practice. Assessment of the changes in selected immunological parameters, including the laboratory ones. Methods: Non-interventional, multicenter, retrospective study conducted at 18 private or hospital immunology out-patient departments in the Slovak Republic. The evaluation was based on anonymous data collection about adult and pediatric patients obtained from routine clinical practice of the out-patient departments; the patients had to receive at least one dose of IMMODIN®between February 2012 and September 2014. The results of routinely performed medical examinations and information about used immunomodulatory therapy, were collected for a period of 12 months prior and after the first IMMODIN®administration.  Results: In total, 133 patients (48 male (36,1%) and 85 female (63,9%)) fulfilled inclusion criteria and their data has been collected. The most frequently reported indications involved recurrent chronic infections (27,2%), followed by chronic fatigue syndrome (22,4%) and severe states of allergic origin with a proven defective cellular immunity (7,1%). Evaluation of the effectiveness parameters confirmed a statistically significant decrease in the absolute number of respiratory (p< 0,0001), urogenital and skin infections (p< 0,05).  Conclusions: The recurrent infection is one of the main reason why patients having immunodeficiency seek medical attention. The presence of recurrent infections decrease the quality of life. The treatment using IMMODIN® significantly lowered the frequency of recurrent respiratory, urogenital or skin infection incidence. Therefore the treatment of patients with recurrent infection using IMMODIN® seems to be valuable alternative to improve their health outcomes and to increase their quality of life. PSY18 Real-World Evidence of Ruxolitinib In The Treatment of Myelofibrosis: Experince of A Portuguese Hospital Center Almeida A1, Alnajjar K1, Viriato D2 Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal, 2Novartis Farma – Produtos Farmacêuticos S.A., Porto Salvo, Portugal

1Instituto

Objectives: Myelofibrosis (MF) is a myeloproliferative disorder characterized by progressive scarring of the bone marrow, splenomegaly and debilitating symptoms. Ruxolitinib, a JAK2 inhibitor, demonstrated rapid and sustained reductions of spleen size and control of MF-related symptoms. This analysis aimed to characterize MF patients treated with ruxolitinib in the real-world setting.  Methods: Data from a Portuguese hospital were collected prospectively (2013-2015) and included MF patients with splenomegaly refractory to cytotoxic agents and/or the presence of constitutional symptoms, under treatment with ruxolitinib. MPN-SAF TSS was used to assess symptoms and QoL. Data were collected at baseline and after 1, 3, 6 and 12 months of treatment.  Results: The registry included 15 patients (86.7% male), with a median age of 68 years. At diagnosis, 80% of patients had primary MF, 6.7% post-polycythemia vera MF and 13.3% post-essential thrombocythemia MF. Risk score DIPSS (Dynamic International Prognostic Scoring System) was classified as intermediate-1 in 40% of patients and intermediate-2 in 60%. At baseline, the median spleen size of patients was 15cm (0cm - 30cm). After starting treatment with ruxolitinib, there was an average (median) reduction of 67% (80%) at the first month and 75% (83%) after one year. The most common adverse events were grade 1 and 2, with anemia as the most frequent (92.9%). Half of the patients experienced anemia G3-4 (n= 14). There were no records of neutropenia and thrombocytopenia G3-4. Ruxolitinib also provided significant improvement of MF-related symptoms, including pain, fatigue, night sweats and itching. Seven out of eleven patients who completed MPN-SAF TSS experienced an improvement in the overall QoL.  Conclusions: Ruxolitinib demonstrated to be an effective therapeutic alternative in reducing splenomegaly in MF patients, with a well-tolerated safety profile. Most patients experienced an improvement in symptoms and quality of life. PSY19 Treatment Comparative Effectiveness In Rare Diseases: The Case of Transthyretin Familial Amyloid Polyneuropathy Survival Inês M1, Coelho T2, Conceição I3, Saramago Goncalves P4, Carvalho M3, Costa J5 de Medicina Molecular, Lisboa, Portugal, 2Unidade Clinica de Paramiloidose, Hospital de Santo Antonio, Porto, Portugal, 3Centro Hospitalar de Lisboa Norte, Lisbon, Portugal, 4University

1Instituto

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of York, Heslington, York, UK, 5Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal

Objectives: This study aims to estimate long-term survival in transthyretin familial amyloid polyneuropathy (TTR-FAP) rare disease using data from the largest and oldest worldwide patient’s cluster as treatment comparative effectiveness is very scarce.  Methods: Registry data from the Portuguese TTR-FAP referral centres were merged encompassing Val30Met patients followed until Dec2015. Three different cohorts were compared: untreated patients with disease onset between 1969 and 1992 (n= 945), liver transplant (LTx) with intervention at stage 1 (n= 935) and disease modifying oral tafamidis treated stage 1 patients with less 65 years age (n= 331). Kaplan-Meier survival estimates were obtained and Cox proportional hazards model with delayed entry were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted by sex, late-onset, disease duration and treatment.  Results: Untreated patients have a median survival of 11.57 years (95%CI: 11.19-11.87) and treated with LTx of 24.73 years (95%CI: 22.90-27.09). Median survival was not reached in the tafamidis group, with 10 years’ survival rate 95.67% (95%CI: 87.49%-98.54%). LTx (HR 0.12, 95%CI: 0.09-0.15) and tafamidis (HR 0.05; 95%CI: 0.020.14) are associated with increased survival, compared with untreated patients. Being a late-onset patient and disease duration at treatment initiation are risk factors associated with increased mortality. No significant statistical effect was found for sex.  Conclusions: Whereas still considered poor, substantial increases in long-term survival of TTR-FAP patients have been observed over the last decades. Although with higher short-term mortality, LTx significantly improved long-term survival. Tafamidis is associated with higher survival though longer follow-up data is still needed. Shorter time between disease onset and treatment is associated with increased survival. In case of clinical progression under drug treatment it’s important to further assess how and when to cross-over to other options such as LTx in order to maximize long-term survival from sequential treatments, with patients in the centre of medical decision making. PSY20 Characteristics, Resources Utilization And Safety Profile of Patients with Acute Pain: A European Real World Evidence Study Katz P1, Pegoraro V2, Heiman F2, Liedgens H1 GmbH, Aachen, Germany, 2IMS Health Information Solutions Italy S.r.l., Milan, Italy

1Grünenthal

Objectives: To identify characteristics, resources utilization and safety profile of patients with acute pain prescribed with Lidocaine 5% plasters, Pregabalin, Gabapentin, Amitriptyline, Duloxetine.  Methods: Retrospective analysis on Real World Data from IMS Health Longitudinal Patient Database in Italy, Germany, UK, Spain, Belgium. All patients with at least one prescription of the drugs of interest during 2014 were selected. Patients with a diagnosis not compatible with pain, patients previously treated with the drugs of interest and patients treated with more than one drug of interest were excluded. For each patient, demographic and clinical characteristics, co-prescriptions, examinations, specialist visits and hospitalizations were collected. Adverse Drug Reactions (ADRs) as described in the leaflet were searched to evaluate patients’ safety profile. Multivariate logistic models were implemented to understand whether there was an association between treatments and ADRs occurrence.  Results: Patients were selected from Italy (11,287), Germany (5,604), UK (70,515), Spain (10,700 ) and Belgium (2,513). In all countries, patients treated with Lidocaine 5% plasters were older than those in the other groups and more women were treated with Lidocaine 5% plasters, Amitriptyline and Duloxetine than with Pregabalin and Gabapentin. Lidocaine 5% plasters patients had fewer co-medication prescriptions, but no relevant differences were found in the number of specialist visits, examinations and hospitalizations. Compared to all other treatments, significantly less Lidocaine 5% plasters patients experienced at least one ADR in all countries, with odds ratios in favor of Lidocaine 5% plasters, ranging from 3.41 (p= 0.036) to 52.33 (p< 0.001).  Conclusions: Although Lidocaine 5% plasters treated patients were older, their resources utilization profile was comparable to those of the other treatments, but their likelihood of experiencing ADRs was significantly lower. These Real World Data confirm the findings from clinical and observational studies with the Lidocaine 5% plaster. PSY21 A Population-Based Cohort of Gaucher Disease Patients Identified Using EHR Data Jaffe DH1, Flaks-Manov N2, Benis A2, Gabay H2, DiBonaventura M3, Rosenbaum H4, Joseph A5, Leventer-Roberts M2 1Kantar Health, Jerusalem, Israel, 2Clalit Research Institute, Clalit Health Services, Tel Aviv, Israel, 3Kantar Health, New York, NY, USA, 4Clalit Health Services, Nazareth, Israel, 5Shire International GmbH, Zug, Switzerland

Objectives: To characterize a population-based cohort of patients with Gaucher disease (GD) relative to the general population and assesses socio-demographic and clinical differences by disease severity as defined by use of enzyme replacement therapy (ERT).  Methods: A cross-sectional study was conducted using the Clalit Health Services’ (Clalit) electronic health record (EHR) database to identify the prevalence of GD cases as of 30/6/2014. Cases were identified using a combination of International Classification of Diseases codes, 9th revision and associated free text, internally and externally validated registries, laboratory tests, and medication use. Demographics and clinical characteristics are presented for all GD patients by ERT initiation (+/-) and for the general Clalit population. Differences by ERT initiation were tested using chi-square tests.  Results: We identified 500 GD patients in the Clalit database as of the index date. The prevalence of GD ranged from 5.3 per 100,000 for members aged ≤ 34 years old to 20.2 per 100,000 in ≥ 35-year-olds. The majority of GD patients were ≥ 18 years old (91.6%), female (54.0%), and of higher socioeconomic status relative to the general Clalit population (GD= 34.8% vs. Clalit= 19.0%). The prevalence of overweight/obesity was 51.0% among GD patients and 46.5% among all Clalit members. Only 35.0% of GD patients had a Charlson Comorbidity Index (CCI)< 1 compared with 68.2% in the general population. Among GD patients, no differences were observed by ERT initiation status for socio-demographic

or clinical characteristics with the exception of CCI< 1 (ERT+= 19.9% vs. ERT-= 45.6%; p< 0.001). Prior to ERT treatment, anemia, thrombocytopenia and hepatomegaly were more common in ERT+ than ERT- patients (p< 0.02).  Conclusions: This is the first study to have detailed socio-economic and clinical data on a large GD cohort using a comprehensive real-time EHR database. Establishing such a cohort is critical to understanding disease burden and outcomes in a real-world population. PSY22 A Retrospective, Cross Sectional Study on The Prevalence of Hyperuricemia Using A Healthcare Database In Japan Higa S1, Yoshida M1, Shima D1, Ii Y1, Kitazaki S2, Yamamoto Y2, Fujimoto Y1 1Pfizer Japan Inc, Tokyo, Japan, 2MinaCare co.ltd, Tokyo, Japan

Background: The prevalence of hyperuricemia (HU) is likely to be underestimated in Japan as previous studies reporting on prevalence have been based only on health checkup data and did not take into account anti-hyperuricemic medication use and its effect on serum uric acid (SUA) levels.  Objectives: To estimate more accurately the prevalence of HU in Japan by taking into account HU patients receiving drug therapy.  Methods: The MinaCare database, which includes linked health checkup and claims data, was used to estimate prevalence of HU. The study population consisted of subjects who had at least one SUA measurement from health checkup data between fiscal years (FY) 2010-2014 (FY= April 1st – March 31st). HU was defined as an SUA level >  7.0 mg/dL in health checkup data and/or a prescription of anti-hyperuricemic medication in claims data.  Results: The prevalence of HU in FY 2014 was 26.8% (95% confidence interval [CI]: 26.2~27.3%) in male subjects and 0.9% (95% CI: 0.7~1.0%) in female subjects. Overall, prevalence increased with the advancement in age (Prevalence in males was 19.8%, 25.1%, 27.1%, 29.4%, 29.5%, 30.6% and in females was 0.2%, 0.6%, 0.9%, 1.7%, 1.6%, 3.5% for age groups of < 30, 30-< 40, 40-< 50, 50-< 60, 60-< 65, > 65, respectively) and the prevalence of HU was higher in subjects with high BMI, hypertension or hyperlipidemia. Similar results were observed in other FY periods.  Conclusions: This is the first study of the prevalence of HU in Japan that takes into account both SUA levels and therapeutic status. The prevalence was higher than what has been reported in previous studies and it is considered to be a more accurate estimate of HU prevalence. PSY23 The Prevalence of Plaque Psoriasis, Psoriatic Arthritis And The Overlap Between Them In Norway Polyzoi M1, Virhage M1, Geale K2, Anell B1 International, Stockholm, Sweden, 2Umeå University, Umeå, Sweden

1PAREXEL

Introduction: Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic diseases that affect 1.5% to 8.5% and 8% to 21% of the Norwegian population, respectively, according to estimates in recent studies. The most common type of PsO is plaque psoriasis and the majority of patients with PsA also suffer from PsO. The disease burden of PsO and PsA are substantial and comparable to other major severe chronic diseases such as diabetes and rheumatoid arthritis. Patients with moderate to severe PsO and PsA are routinely referred from primary care to specialist care services.  Objectives: The objective of this study was to estimate the prevalence of moderate to severe plaque psoriasis and PsA, and the overlap between them, as reported diagnosis in the National Patient Registry (NPR) in Norway.  Methods: The total numbers of unique adult patients with main diagnoses of PsO and PsA (ICD-10 codes: L40+) in 2014, hospitalized or in contact with specialist services, were extracted from the NPR. Based on the Norwegian general population in 2014 (n= 5,109,056), the prevalence of each disease was estimated.  Results: The prevalence of moderate to severe plaque psoriasis was estimated to 0.14%. The prevalence of PsA was estimated to 0.18%, while the prevalence of the coexistence of moderate to severe plaque psoriasis and PsA equaled 0.02%.  Conclusions: Since the milder PsO cases are treated in the primary care setting in Norway, the prevalence of plaque psoriasis reported in this study reflected the moderate to severe cases with registered visits to specialist health services. This population constitutes approximately 10% of the total PsO population, based on the literature. The results indicate that very few of the estimated prevalent PsO patients are treated by specialists. Also, to our knowledge this is the first study reporting the prevalence of PsO and PsA in specialist care services in Norway. PSY24 Incidence And Prevalence of Multiple Myeloma From 2016 To 2020 According To The Treatment Line And Hematopoietic Stem Cell Transplantation Status Bouee S1, Fénéron-Chevé D2, Trancart M3, Gaudin A4 La Reine, France, 2Health Economics, Rueil-Malmaison, France, 3CEMKA-EVAL, Bourg La Reine, France, 4Bristol-Myers Squibb, Rueil-Malmaison, France

1CEMKA, Bourg

Objectives: The epidemiologic information on cancers are generally reported in terms of incidence. However, prevalence data are complementary to estimate the burden of the disease on the healthcare system. The objective of this model was to estimate the incidence and prevalence of patients suffering from multiple myeloma (MM) from 2016 to 2020, according to the treatment line and to the hematopoietic stem cell transplantation (HSCT) status.  Methods: An epidemiological model was developed from incidence rate since 1990, relapse rate after a first line and a secondline treatment (based on overall and progression free survival observed in clinical trials). This exponential survival model allowed to estimate yearly the incidence, the prevalence, and the number of patients joining a second or third line and more of therapy.  Results: The incidence of MM was expected to be 5,178 in 2016 and 5,485 in 2020, a 5,9% increase in 4 years. Excluding patients not needing treatment, 4,525 patients were expected to receive a first-line treatment in 2020 including 3,538 treated only by drugs therapy and 987 by drugs therapy+HSCT. The number of patients requiring a second line and a third-line or more of chemotherapy was respectively expected to be 1,635 and 1,579 in 2020 (+12.9% vs 2016). Overall, 6,752 patients would initiate a new MM chemotherapy in 2020. The prevalence of treated MM patients is expected to increase from 27,121 in 2016 to 30,263 in 2020 (+11.6%)