Blinatumomab vs historic standard-of-care treatment for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukaemia.

OBJECTIVES: Survival outcomes from a single-arm phase 2 blinatumomab study in patients with minimal residual disease (MRD)-positive B-cell precursor (BCP)-acute lymphoblastic leukaemia (ALL) were compared with those receiving standard of care (SOC) in a historic data set. METHODS: The primary analysis comprised adult Philadelphia chromosome (Ph)-negative patients in first complete haematologic remission (MRD ≥ 10-3 ). Relapse-free survival (RFS) and overall survival (OS) were compared between blinatumomab- and SOC-treatment groups. Baseline differences between groups were adjusted by propensity scores. RESULTS: The primary analysis included 73 and 182 patients from the blinatumomab and historic data sets, respectively. When weighted by age to the blinatumomab-treatment group, median RFS was 7.8 months and median OS was 25.9 months in the SOC-treated group. In the blinatumomab study, median RFS was 35.2 months; median OS was not evaluable. Propensity score weighting achieved balance with seven baseline prognostic factors. With adjustment for haematopoietic stem cell transplantation (HSCT) status, a 50% reduction in risk of relapse or death was observed with blinatumomab vs SOC. Median RFS, unadjusted for HSCT status, was 35.2 months with blinatumomab and 8.3 months with SOC. CONCLUSIONS: These analyses suggest that blinatumomab improves RFS, and possibly OS, in adults with MRD-positive Ph-negative BCP-ALL vs SOC.

A large observational study of patients with primary immune thrombocytopenia receiving romiplostim in European clinical practice.

OBJECTIVE: Romiplostim has maintained long-term platelet counts in patients with immune thrombocytopenia (ITP) for up to 5 yr in clinical studies. This prospective observational study aimed to describe romiplostim utilisation and outcomes in European clinical practice. METHODS: Adults with primary ITP who received romiplostim in routine care were eligible. RESULTS: Three-hundred and forty patients were eligible for analysis, of whom 299 (88%) completed the 2-yr observation period. The median age was 62 yr, with 43% of patients aged ≥65 yr, and two-thirds of patients initiated romiplostim before splenectomy. The median average weekly dose of romiplostim was 2.8 µg/kg. The median baseline platelet count was 20 × 109 /L, which increased after 2 wk of romiplostim treatment and remained >50 × 109 /L thereafter. After romiplostim initiation, there was a decrease in rates of grade ≥3 bleeding events (from 12 to 2 per 100 patient-years) and ITP-related hospitalisations (from 87 to 33 per 100 patient-years). The rate of thrombotic events was 2 per 100 patient-years, and bone marrow fibrosis occurred in two patients. CONCLUSIONS: Romiplostim dosing, effectiveness and safety in an unselected real-world ITP population seemed comparable with that observed in clinical studies.

The DA VINCI study: is Ireland achieving ESC/EAS guideline-directed LDL-C goals?

BACKGROUND: The EU-wide, cross-sectional observational study of lipid-lowering therapy (LLT) use in secondary and primary care (DA VINCI) assessed the proportion of patients achieving low-density lipoprotein cholesterol (LDL-C) goals recommended by the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines and provided an insight into regional use of LLT in Europe, including Ireland. AIMS: This analysis focuses on data from patients in Ireland who participated in the DA VINCI study. METHODS: The DA VINCI study enrolled patients receiving LLT at primary and secondary care sites across 18 European countries between June 2017 and November 2018. The study assessed the achievement of risk-based 2016 and 2019 ESC/EAS LDL-C goals. This subgroup analysis aimed to evaluate LDL-C goal attainment in an Irish cohort of primary and secondary care patients. RESULTS: In total, 198 patients from Ireland were enrolled from three primary care and three secondary care centres. Most patients were White and male, and were receiving moderate- or high-intensity statin therapy (most frequently atorvastatin or rosuvastatin). Few patients (< 10%) were receiving combination therapy of statin and ezetimibe. Approximately 60% of patients achieved their 2016 ESC/EAC LDL-C goals while less than half the patients achieved their 2019 ESC/EAS goals. Approximately half of secondary prevention patients achieved their 2016 ESC/EAS goals and only 20% of secondary prevention patients achieved their 2019 ESC/EAS goals. CONCLUSIONS: These results highlight the disparity between dyslipidaemia management in clinical practice in Ireland and guideline recommendations. TRIAL REGISTRATION: ENCePP; EU PAS 22,075; date registered 06 February 2018.

Minimal residual disease level predicts outcome in adults with Ph-negative B-precursor acute lymphoblastic leukemia.

OBJECTIVES: Detectable minimal residual disease (MRD) after therapy for acute lymphoblastic leukemia (ALL) is the strongest predictor of hematologic relapse. This study evaluated outcomes of patients with B-cell precursor ALL with MRD of ≥10-4 Methods: Study population was from ALL study groups in Europe managed in national study protocols 2000-2014. MRD was measured by polymerase chain reaction or flow cytometry. Patients were age ≥15 years at initial ALL diagnosis. Patients were excluded if exposed to blinatumomab within 18 months of baseline or prior alloHSCT. RESULTS: Of 272 patients in CR1, baseline MRD was ≥10-1, 10-2 to <10-1, 10-3 to <10-2, and 10-4 to <10-3 in 15 (6%), 71 (26%), 109 (40%), and 77 (28%) patients, respectively. Median duration of complete remission (DoR) was 18.5 months (95% confidence interval [CI], 11.9-27.2), median relapse-free survival (RFS) was 12.4 months (95% CI, 10.0-19.0) and median overall survival (OS) was 32.5 months (95% CI, 23.6-48.0). Lower baseline MRD level (P ≤ .0003) and white blood cell count <30,000/µL at diagnosis (P ≤ .0053) were strong predictors for better RFS and DoR. Allogeneic hematopoietic stem cell transplantation (alloHSCT) was associated with longer RFS (hazard ratio [HR], 0.59; 95% CI, 0.41-0.84) and DoR (HR, 0.43; 95% CI, 0.29-0.64); the association with OS was not significant (HR, 0.72; 95% CI, 0.50-1.05). DISCUSSION: In conclusion, RFS, DoR, and OS are relatively short in patients with MRD-positive ALL, particularly at higher MRD levels. AlloHSCT may improve survival but has limitations. Alternative approaches are needed to improve outcomes in MRD-positive ALL.

Sources of European drug consumption data at a country level.

OBJECTIVES: This study aimed at outlining the characteristics of nationwide administrative databases monitoring drug consumption in Europe. METHODS: Internet and bibliographic databases (April 2010) were searched and experts in drug utilization (DU) research interviewed to find nationwide administrative medicines consumption databases in Europe, with data for the out- and inpatient healthcare sector. A questionnaire was developed to gather additional information. We collected data providers, websites, accessibility, data sources, healthcare settings, population coverage, medicines-related data, patient and prescriber data, periods covered, and linkage to other databases. RESULTS: Thirty-one administrative nationwide medicine consumption databases in 25 countries were identified. Questionnaires were responded for 20 databases. Eleven provided wholesalers' sales data, 11 on reimbursed, 5 on prescribed, and 4 on dispensing medicines. Fifteen databases provided inpatient drug consumption data, mainly wholesalers' sales. CONCLUSIONS: Nationwide administrative databases are of value to all stakeholders involved in the conduct and interpretation of post-marketing safety studies, and in the conduct of DU research. The endorsement of the anatomical therapeutic chemical/defined daily dose methodology by these databases contributes to data harmonization. However, there is still a lack of information on inpatient medicines consumption at a patient-level.

A compilation of research working groups on drug utilisation across Europe.

BACKGROUND: The assessment of the benefit-risk of medicines needs careful consideration concerning their patterns of utilization. Systems for the monitoring of medicines consumption have been established in many European countries, and several international groups have identified and described them. No other compilation of European working groups has been published. As part of the PROTECT project, as a first step in searching for European data sources on the consumption of five selected groups of medicines, we aimed to identify and describe the main characteristics of the existing collaborative European working groups. FINDINGS: Google and bibliographic searches (PubMed) of articles containing information on databases and other sources of drug consumption data were conducted. For each working group the main characteristics were recorded.Nineteen selected groups were identified, focusing on: a) general drug utilisation (DU) research (EuroDURG, CNC, ISPE'S SIG-DUR, EURO-MED-STAT, PIPERSKA Group, NorPEN, ENCePP, DURQUIM), b) specific DU research: b.1) antimicrobial drugs (ARPAC, ESAC, ARPEC, ESGAP, HAPPY AUDIT), b.2) cardiovascular disease (ARITMO, EUROASPIRE), b.3) paediatrics (TEDDY), and b.4) mental health/central nervous system effects (ESEMeD, DRUID, TUPP/EUPoMMe). Information on their aims, methods and activities is presented. CONCLUSIONS: We assembled and updated information on European working groups in DU research and in the utilisation of five selected groups of drugs for the PROTECT project. This information should be useful for academic researchers, regulatory and health authorities, and pharmaceutical companies conducting and interpreting post-authorisation and safety studies. European health authorities should encourage national research and collaborations in this important field for public health.

The burden of immune thrombocytopenia in adults: evaluation of the thrombopoietin receptor agonist romiplostim.

BACKGROUND: Immune thrombocytopenia (ITP) is a chronic, immune-mediated disease characterized by a transient or long-lasting decrease in platelet counts. ITP is associated with numerous serious clinical consequences. Discussed here are clinical aspects of ITP, the humanistic and economic burden of ITP, and current treatment options with a focus on romiplostim, a thrombopoietin (TPO) receptor agonist. The aim of this review is to provide decision-makers with the background information necessary to evaluate the value of romiplostim. SCOPE: PubMed was searched for relevant, English-language papers published from January 2006 through November 2011 relating to the epidemiology and treatment options of chronic ITP, and, focusing on the TPO mimetic romiplostim, patient-reported outcomes (PRO) and economic burden. Recent select conference abstracts were also reviewed. FINDINGS: The initial clinical management of ITP (e.g., corticosteroids, immunoglobulins) is often associated with adverse events and recommended for short-term use only. Splenectomy, a potentially curative second-line treatment, is associated with increased risks of bleeding and infection, and patients often require additional long-term drug intervention. ITP and its sequelae are associated with a substantial burden on patients' health-related quality-of-life (HRQoL) and increased medical costs. Use of TPO receptor agonists in ITP patients may represent a more efficient use of healthcare resources than existing therapies. CONCLUSION: While this literature review is not a systematic review, e.g., it considers only approved therapies and published literature written in English, it provides a comprehensive overview of the clinical, humanistic, and economic factors that should be considered in treating ITP, particularly with new agents such as romiplostim. Among the limited number of safe and effective therapies currently available for chronic ITP, highly effective and well-tolerated medications such as romiplostim may reduce the healthcare resource utilization associated with ITP while improving patients' HRQoL.

Quality of urological cancer diagnoses in the Danish National Registry of Patients.

Valid and up-to-date data on cancer diagnoses are needed for clinical quality monitoring and epidemiological research. The Danish National Registry of Patients (DNRP) is continuously updated, recording all Danish hospital contacts including cancer diagnoses. The Danish Cancer Registry (DCR) is updated once a year and includes quality control of diagnoses. We compared the quality of urological cancer diagnoses in the DNRP with the DCR to assess whether data in an administrative hospital registry are valid compared with data from a well-established cancer registry. We identified 60 434 incident urological cancer cases in the DNRP and/or the DCR from 2001 to 2009. Completeness and the positive predictive value (PPV) of urological cancer registration in the DNRP were estimated using the DCR as the reference standard. To examine the impact of potential misclassification, we computed mortality estimates for urological cancer patients in each registry. Because DCR registration procedures changed in 2004, the periods 2001-2003 and 2004-2009 were analyzed separately. In 2004-2009, the overall completeness and PPV of urological cancer registration in the DNRP were 94.9% (95% confidence interval: 94.7-95.2%) and 86.6% (95% confidence interval: 86.3-86.9%), respectively, compared with diagnoses recorded in the DCR. Completeness and PPV of cancer registration in the DNRP varied between cancer subgroups. In 2001-2003, both completeness and PPV in the DNRP were slightly lower compared with 2004-2009. Mortality estimates in patients registered in the DNRP and the DCR varied slightly. The DNRP could be a valuable source of data for clinical quality monitoring and epidemiological research for some urological cancers, especially when current data are essential.