Post-Authorization Safety Studies of Acute Liver Injury and Severe Complications of Urinary Tract Infection in Patients with Type 2 Diabetes Exposed to Dapagliflozin in a Real-World Setting.

INTRODUCTION: At the time of dapagliflozin's approval in Europe (2012) to treat patients with type 2 diabetes mellitus, concerns regarding acute liver injury and severe complications of urinary tract infection (sUTI) led to two post-authorization safety (PAS) studies of these outcomes to monitor the safety of dapagliflozin in real-world use. OBJECTIVE: To investigate the incidence of hospitalization for acute liver injury (hALI) or sUTI (pyelonephritis or urosepsis) among patients initiating dapagliflozin compared with other glucose-lowering drugs (GLDs). METHODS: These two noninterventional cohort studies identified initiators of dapagliflozin and comparator GLDs in November 2012-February 2019 using data from three longitudinal, population-based data sources: Clinical Practice Research Datalink (UK), the HealthCore Integrated Research Database (USA), and the Medicare database (USA). Outcomes (hALI and sUTI) were identified with electronic algorithms. Incidence rates were estimated by exposure group. Incidence rate ratios (IRRs) were calculated comparing dapagliflozin to comparator GLDs, using propensity score trimming and stratification to address confounding. The sUTI analyses were conducted separately by sex. RESULTS: In all data sources, hALI and sUTI incidence rates were generally lower in dapagliflozin initiators than comparator GLD initiators. The adjusted IRR (95% confidence interval) pooled across data sources for hALI was 0.85 (0.59-1.24) and for sUTI was 0.76 (0.60-0.96) in females and 0.74 (0.56-1.00) in males. Findings from sensitivity analyses were largely consistent with the primary analyses. CONCLUSIONS: These real-world studies do not suggest increased risks of hALI or sUTI, and they suggest a potential decreased risk of sUTI with dapagliflozin exposure compared with other GLDs.

Post-Authorization Safety Study of Hospitalization for Acute Kidney Injury in Patients with Type 2 Diabetes Exposed to Dapagliflozin in a Real-World Setting.

INTRODUCTION: Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor approved to treat type 2 diabetes mellitus (T2DM), among other conditions. When dapagliflozin was approved in Europe for treating T2DM (2012), potential safety concerns regarding its effect on kidney function resulted in this post-authorization safety study to assess hospitalization for acute kidney injury (hAKI) among dapagliflozin initiators in a real-world setting. OBJECTIVE: The aim of this study was to evaluate the incidence of hAKI in adults with T2DM initiating dapagliflozin compared with other glucose-lowering drugs (GLDs). METHODS: This noninterventional cohort study identified new users of dapagliflozin and comparator GLDs from November 2012 to February 2019 from three longitudinal, population-based data sources: Clinical Practice Research Datalink (CPRD; United Kingdom), the HealthCore Integrated Research Database (HIRD; United States [US]), and Medicare (US). Electronic algorithms identified occurrences of hAKI, from which a sample underwent validation. Incidence rates for hAKI were calculated, and incidence rate ratios (IRRs) compared hAKI in dapagliflozin with comparator GLDs. Propensity score trimming and stratification were conducted for confounding adjustment. RESULTS: In all data sources, dapagliflozin initiators had a lower hAKI incidence rate than comparator GLD initiators (adjusted IRRs: CPRD, 0.44 [95% confidence interval (CI), 0.22-0.86]; HIRD, 0.76 [95% CI, 0.62-0.93]; Medicare, 0.69 [95% CI, 0.59-0.79]). The adjusted IRR pooled across the data sources was 0.70 (95% CI, 0.62-0.78). Results from sensitivity and stratified analyses were consistent with the primary analysis. CONCLUSIONS: This study, with > 34,000 person-years of real-world dapagliflozin exposure, suggests a decreased risk of hAKI in patients with T2DM exposed to dapagliflozin, aligning with results from dapagliflozin clinical trials. STUDY REGISTRATION: European Union Post-Authorisation Studies Register, EUPAS 11684; ClinicalTrials.gov, NCT02695082.

Incidence of safety events after immune checkpoint inhibitor initiation for advanced-stage non-small-cell lung cancer: a real-world study.

Aim: To describe the incidence of safety events after immune checkpoint inhibitor (ICI) initiation for advanced-stage non-small-cell lung cancer. Methods: Retrospective cohort study using the HealthCore Integrated Research Database in the USA to examine the incidence of prespecified safety events of interest after ICI initiation (n = 5278). Results: The most common safety events after ICI initiation included malaise/fatigue (incidence rate [IR]: 70.7 per 100 person-years; 95% CI: 66.5-75.1) and nausea/vomiting (IR: 32.4; 30.0-34.8). Other potential immune-mediated events, including colitis (IR: 7.11; 6.26-8.04) and pneumonitis (IR: 5.47; 4.76-6.25), were less frequent but higher than after any systemic anti-cancer therapy. No safety event rate substantially increased 6 months after ICI initiation. Conclusion: This large real-world study reports the incidence of safety events with ICI regimens for advanced-stage non-small-cell lung cancer.

Researchers wanted to investigate side effects identified with advanced lung cancer during treatment, particularly immunotherapy. To investigate these side effects, researchers examined health insurance claims records from patients who were diagnosed with advanced lung cancer between January 2010 and July 2019, and who received treatment at various clinics across the USA. Researchers identified records for 44,045 patients treated for advanced lung cancer, with 5278 being treated with immunotherapy. After patients started immunotherapy, the most commonly reported side effects were tiredness and nausea/vomiting. Other side effects possibly related to immunotherapy were inflammation of the large intestine and lung inflammation ­ these events were not reported very often and did not increase in frequency 6 months after start of treatment. This large real-world study provides estimates for the frequency of side effects for those treated for advanced lung cancer, and finds that there were no large increases in the occurrence of any particular side effect in the 6 months after patients started immunotherapy for advanced lung cancer.

Health care resource utilization and costs associated with advanced or metastatic nonsmall cell lung cancer in the United States.

BACKGROUND: The treatment landscape for advanced nonsmall cell lung cancer (NSCLC) has evolved from 2015 onward, since the introduction of immune checkpoint inhibitors (ICIs). Considering this shift, there have been limited prior analyses that assess the economic burden of NSCLC within the current treatment landscape. OBJECTIVE: To present an analysis of health care resource utilization (HCRU) and costs associated with the treatment of patients with advanced or metastatic NSCLC in the United States between 2010 and 2019. METHODS: Patients with locally advanced or metastatic NSCLC who initiated first-line (1L) systemic treatment between January 1, 2010, and June 30, 2019, were included from the HealthCore Integrated Research Database using a previously developed claims-based predictive model algorithm. Mean total HCRU and costs and mean per-person-per-year (PPPY) HCRU and costs were estimated for 2 follow-up periods: the time during the entire follow-up period and the time during the 1L treatment period. Distribution of treatment classes (defined as chemotherapy, ICIs, targeted therapies, and others) were also analyzed by index year. RESULTS: 27,257 patients met the eligibility criteria and were included in the analysis. The mean duration of follow-up for all patients was 16.6 months (median 10.6 months), and the median time to discontinuation of 1L treatment was 2.8 months. The number of outpatient visits accounted for the majority of HCRU across the entire study follow-up (mean 97.7 in total and 147.1 PPPY) and for the 1L treatment period (mean 46.3 in total and 167.5 PPPY). The total mean cost across the entire study follow-up was $158,908 ($250,942 PPPY). For the 1L treatment period, the total mean cost was $72,760 ($271,590 PPPY). Total mean outpatient costs for systemic anticancer treatment were $61,797 for the entire study follow-up ($85,609 PPPY) and $27,138 during the 1L treatment period ($92,412 PPPY). Total costs increased over the study duration, which were mainly due to increasing outpatient costs for systemic therapy. In both follow-up periods, inpatient costs, other outpatient costs (nonsystemic therapy-related costs), and pharmacy costs remained relatively stable but still accounted for more than 60% of the total costs. Analysis of treatment classes over time showed that chemotherapy was the most frequently used treatment, regardless of line of therapy. A trend was observed for increased ICI use from 2015 onward. CONCLUSIONS: Despite the improvement in treatment options, a high economic burden associated with the treatment of NSCLC still exists. The total costs have been increasing, mainly driven by outpatient costs for systemic therapy, which might reflect the greater use of ICIs for advanced NSCLC. Costs for inpatient services, other outpatient services, and pharmacy services remained stable but still accounted for the majority of the economic burden. Further studies are required to assess the impact of innovative treatments on the disease management costs of advanced NSCLC. DISCLOSURES: This study was funded by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945) as part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany, and Pfizer. Zhang, Liu, and Yang are employees of EMD Serono. Beachler, Dinh, and Jamal-Allial are employees of HealthCore Inc., which received funding from the healthcare business of Merck KGaA, Darmstadt, Germany, and Pfizer for the implementation of this study. Masters and Kolitsopoulos are employees of Pfizer. Lamy was an employee of the healthcare business of Merck KGaA, Darmstadt, Germany, at the time this study was conducted.

A real-world study on characteristics, treatments and outcomes in US patients with advanced stage ovarian cancer.

BACKGROUND: Detailed epidemiologic descriptions of large populations of advanced stage ovarian cancer patients have been lacking to date. This study aimed to describe the patient characteristics, treatment patterns, survival, and incidence rates of health outcomes of interest (HOI) in a large cohort of advanced stage ovarian cancer patients in the United States (US). METHODS: This cohort study identified incident advanced stage (III/IV) ovarian cancer patients in the US diagnosed from 2010 to 2018 in the HealthCore Integrated Research Database (HIRD) using a validated predictive model algorithm. Descriptive characteristics were presented overall and by treatment line. The incidence rates and 95% confidence intervals for pre-specified HOIs were evaluated after advanced stage diagnosis. Overall survival, time to treatment discontinuation or death (TTD), and time to next treatment or death (TTNT) were defined using treatment information in claims and linkage with the National Death Index. RESULTS: We identified 12,659 patients with incident advanced stage ovarian cancer during the study period. Most patients undergoing treatment received platinum agents (75%) and/or taxanes (70%). The most common HOIs (> 24 per 100 person-years) included abdominal pain, nausea and vomiting, anemia, and serious infections. The median overall survival from diagnosis was 4.5 years, while approximately half of the treated cohort had a first-line time to treatment discontinuation or death (TTD) within the first 4 months, and a time to next treatment or death (TTNT) from first to second-line of about 6 months. CONCLUSIONS: This study describes commercially insured US patients with advanced stage ovarian cancer from 2010 to 2018, and observed diverse treatment patterns, incidence of numerous HOIs, and limited survival in this population.

The Association Between Doctor and Pharmacy Shopping and Self-Reported Misuse and Abuse of Prescription Opioids: A Survey Study.

BACKGROUND/RATIONALE: Little is known about the reasons for visiting multiple doctors/pharmacies, known as doctor/pharmacy shopping, to obtain opioids. OBJECTIVE: To investigate patients' self-reported reasons for doctor/pharmacy shopping and assess whether doctor/pharmacy shopping behavior can be used as a surrogate measure of opioid abuse/misuse. METHODS: We conducted a cross-sectional web-based survey among adult patients with ≥2 pharmacy claims for immediate-release or extended-release/long-acting opioids between 7/1/2015 and 12/31/2016, identified from a large United States (US) commercial claims database. Patients were classified into no, mild, moderate, or severe shopping categories based on their claims. Reasons for doctor/pharmacy shopping and opioid abuse/misuse were determined from patient responses to the Prescription Opioid Misuse and Abuse Questionnaire. RESULTS: A random sample of 10,081 patients was invited to participate in the survey and 1085 (11%) completed surveys. The most frequently reported reasons for doctor/pharmacy shopping were convenience, availability, price, and multiple morbidities requiring pain management. Among patients in the no, minimal, moderate, and severe shopping categories, only 7.8%, 8.5%, 11.8% and 12.6% reported opioid abuse/misuse, respectively. CONCLUSION: In this commercially-insured population, patient-reported reasons for doctor/pharmacy shopping do not suggest opioid abuse/misuse. Less than 15% of patients with shopping behavior in the past 3 months reported any reasons attributable to opioid abuse/misuse, indicating that shopping behavior in this population may not be a good surrogate for abuse/misuse.

Validation of a claims-based algorithm identifying eligible study subjects in the ADAPTABLE pragmatic clinical trial.

OBJECTIVE: Validate an algorithm that uses administrative claims data to identify eligible study subjects for the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness) pragmatic clinical trial (PCT). MATERIALS AND METHODS: This study used medical records from a random sample of patients identified as eligible for the ADAPTABLE trial. The inclusion criteria for ADAPTABLE were a history of acute myocardial infarction (AMI) or percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), or other coronary artery disease (CAD), plus at least one of several risk-enrichment factors. Exclusion criteria included a history of bleeding disorders or aspirin allergy. Using a claims-based algorithm, based on International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM) and 10th Edition (ICD-10) codes and Current Procedural Terminology (CPT) codes, we identified patients eligible for the PCT. The primary outcome was the positive predictive value (PPV) of the identification algorithm: the proportion of sampled patients whose medical records confirmed their ADAPTABLE study eligibility. Exact 95% confidence limits for binomial random variables were calculated for the PPV estimates. RESULTS: Of the 185 patients whose medical records were reviewed, 168 (90.8%; 95% Confidence Interval: 85.7%, 94.6%) were confirmed study eligible. This proportion did not differ between patients identified with codes for AMI and patients identified with codes for PCI or CABG. CONCLUSION: The estimated PPV was similar to those in claims-based identification of drug safety surveillance events, indicating that administrative claims data can accurately identify study-eligible subjects for pragmatic clinical trials.