BBCIC Research Network Analysis of First-Cycle Prophylactic G-CSF Use in Patients Treated With High-Neutropenia Risk Chemotherapy.

BACKGROUND: Chemotherapy-induced febrile neutropenia (FN) is prevented or minimized with granulocyte colony-stimulating factors (G-CSFs). Several G-CSF biosimilars are approved in the United States. The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) is a nonprofit initiative whose objective is to provide scientific evidence on real-world use and comparative safety and effectiveness of biologics and biosimilars using the BBCIC distributed research network (DRN). PATIENTS AND METHODS: We describe real-world G-CSF use in patients with breast or lung cancer receiving first-cycle chemotherapy associated with high FN risk. We assessed hospitalizations for FN, availability of absolute neutrophil counts, and G-CSF-induced adverse events to inform future observational comparative effectiveness studies of G-CSF reference products and their biosimilars. A descriptive analysis of 5 participating national health insurance plans was conducted within the BBCIC DRN. RESULTS: A total of 57,725 patients who received at least one G-CSF dose were included. Most (92.5%) patients received pegfilgrastim. FN hospitalization rates were evaluated by narrow (<0.5%), intermediate (1.91%), and broad (2.99%) definitions. Anaphylaxis and hyperleukocytosis were identified in 1.15% and 2.28% of patients, respectively. This analysis provides real-world evidence extracted from a large, readily available database of diverse patients, characterizing G-CSF reference product use to inform the feasibility of future observational comparative safety and effectiveness analyses of G-CSF biosimilars. We showed that the rates of FN and adverse events in our research network are consistent with those reported by previous small studies. CONCLUSIONS: Readily available BBCIC DRN data can be used to assess G-CSF use with the incidence of FN hospitalizations. Insufficient laboratory result data were available to report absolute neutrophil counts; however, other safety data are available for assessment that provide valuable baseline data regarding the effectiveness and safety of G-CSFs in preparation for comparative effectiveness studies of reference G-CSFs and their biosimilars.

Chemotherapy-induced peripheral neuropathy (CIPN) and its treatment: an NIH Collaboratory study of claims data.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling complication of many chemotherapies. We investigated the feasibility of using health plan claims and administrative data to identify CIPN occurrence by comparing patients who received neurotoxic and non-neurotoxic chemotherapies. METHODS: The sample included over 53,000,000 patients from two regional and one national insurer in the USA (> 400,000 exposed to chemotherapy). Peripheral neuropathy was identified using a broad definition (definition 1) and a specific definition (i.e., drug-induced polyneuropathy code) (definition 2). RESULTS: CIPN incidence as measured by definition 1 within 6 months of chemotherapy initiation was 18.1% and 6.2% for patients who received neurotoxic and non-neurotoxic chemotherapy, respectively (relative risk neurotoxic vs. non-neurotoxic (RR), 2.93 (95% CI, 2.87-2.98)). For definition 2, these incidences were 3.6% and 0.1% (RR, 25.2 (95% CI, 22.8-27.8)). The incidences of new analgesic prescriptions for neurotoxic and non-neurotoxic groups were as follows: gabapentin, 7.1%/1.7%; pregabalin, 0.69%/0.31%; and duloxetine, 0.78%/0.76%. The incidence of CIPN as defined by definitions 1 and 2 was low compared with that of published research studies, but the relative risk of CIPN among patients who received neurotoxic chemotherapies compared with those who received non-neurotoxic chemotherapies was high using definition 2. CONCLUSIONS: These data suggest that as used currently by clinicians, administrative codes likely underestimate CIPN incidence. Thus, studies using administrative data to estimate CIPN incidence are not currently feasible. However, the drug-induced polyneuropathy code is a specific indicator of CIPN in administrative data and may be useful for investigating predictors or potentially preventive therapies of CIPN.

Safety assessment of niacin in the US Food and Drug Administration's mini-sentinel system.

PURPOSE: The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trial found higher incidence rates of adverse reactions, including bleeding, in patients receiving the combination of extended-release niacin and laropiprant versus placebo. It is not known whether these adverse events are attributable to laropiprant, not approved in the USA, or to extended-release niacin. We compared rates of major gastrointestinal bleeding and intracranial hemorrhage among initiators of extended-release niacin and initiators of fenofibrate. METHODS: We used Mini-Sentinel (now Sentinel) to conduct an observational, new user cohort analysis. We included data from 5 Data Partners covering the period from January 1, 2007 to August 31, 2013. Individuals who initiated extended-release niacin were propensity score-matched to individuals who initiated fenofibrate. Within the matched cohorts, we used Cox proportional hazards models to compare rates of hospitalization for major gastrointestinal bleeding events and intracranial hemorrhage assessed using validated claims-based algorithms. RESULTS: A total of 234 242 eligible extended-release niacin initiators were identified, of whom 210 389 (90%) were 1:1 propensity score-matched to eligible fenofibrate initiators. In propensity score-matched analyses, no differences were observed between exposure groups in rates of major gastrointestinal bleeding (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.82 to 1.18) or intracranial hemorrhage (HR, 1.21; 95% CI, 0.66 to 2.22). Results were similar in pre-specified sensitivity and subgroup analyses. CONCLUSIONS: We did not observe evidence for an association between extended-release niacin versus fenofibrate and rates of major gastrointestinal bleeding or intracranial hemorrhage.

Improving immunization coverage in a rural school district in Pierce County, Washington.

Washington State has some of the highest percentages of school immunization exemptions in the country. We compared school immunization records in a rural school district in Pierce County, Washington, to immunization records in the state immunization information system (IIS) and parent-held records. Correcting school immunization records resulted in an increase in the number of students classified as fully immunized from 1,189 to 1,564 (p < .0001). We conducted school-based immunization clinics that increased the number of fully immunized students to 1,624 (p = .013). Immunized students with certificates of exemption on file suggest exemptions of convenience. Strategies to improve school immunization services include assigning IIS access to school administrative staff and educating school staff and parents on the importance of immunization.

Prevalence of cryoglobulinemia in hepatitis C virus (HCV) positive patients with and without human immunodeficiency virus (HIV) coinfection.

BACKGROUND: Coinfection with human immunodeficiency virus (HIV) has been shown to influence the natural history of hepatitis C infection. OBJECTIVE: Our interest was to determine if HIV coinfection influences the prevalence of cryoglobulinemia in hepatitis C virus (HCV) infected persons. STUDY DESIGN: A total of 384 HCV RNA positive (234 HIV-infected and 150 HIV-uninfected) participants were tested at two visits, 18 months apart, for HCV and HIV RNA, CD4, and liver enzyme levels. Serum cryoglobulin levels were measured at a subsequent visit for a subset of the sample. RESULTS: HIV-infected participants had significantly higher HCV RNA levels (P < 0.0001) and aspartate transaminase (AST) levels (P < 0.0001), but not alanine transaminase (ALT) levels (P > 0.05) as compared with HIV-uninfected participants. These findings were consistent at both visits and no significant changes were observed between visits. Fifty (19%) of the 264 participants tested had detectable cryoglobulins. No difference was observed in HIV seropositivity among participants with or without cryoglobulinemia (68% versus 61%; odds ratio = 1.34, P = 0.37). However, among HIV coinfected participants, elevated AST levels (P = 0.04) and lower CD4 levels (P = 0.02) were associated with cryoglobulinemia. CONCLUSIONS: While previously reported associations were found between HIV and coinfection with HCV in this study, we did not find an association between HIV infection and cryoglobulinemia.

Detection of human T-lymphotropic virus (HTLV) tax sequences in New York City blood donors seronegative for HTLV types 1 and 2.

A potential public health concern is the reported detection of the human T-lymphotropic virus (HTLV) tax gene in the lymphocytes of up to 11% of a low-risk group of New York City blood donors (NYBD). This study aimed to independently confirm the prevalence of HTLV tax sequences in 293 NYBD. All NYBD tested negative for antibodies to HTLV types 1 and 2 and HTLV Tax. HTLV tax sequences were not detected in the NYBD lymphocytes. These data demonstrate the lack of HTLV-1 tax in this group of NYBD at low risk for HTLV infection.