Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice.

BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is a potentially serious complication that can lead to chemotherapy dose delays, dose reductions, or discontinuation, and increases the risk of serious bleeding events. The objectives of this study were to characterize the incidence, clinical consequences, and economic costs of CIT in current US clinical practice. METHODS: A retrospective cohort design and data from two US private healthcare claims repositories (01/2010-12/2016) were employed. Study population comprised adults who received selected myelosuppressive chemotherapy regimens for solid tumors or non-Hodgkin's lymphoma. CIT was identified based on: diagnosis code for thrombocytopenia or bleeding; procedure code for platelet transfusion or bleeding control; or drug code for thrombopoietin-receptor agonist. Incidence of CIT was evaluated during the chemotherapy course (max. no. cycles = 8), and associated consequences and costs (2016US$) were evaluated during the cycle of the CIT episode. RESULTS: Among 215,508 cancer chemotherapy patients, CIT incidence during the course (mean no. cycles = 4.6) was 9.7% (95% CI: 9.6-9.8), and ranged from 6.1% (5.9-6.3) for regimens containing cyclophosphamide to 13.5% (12.7-14.3) for regimens containing gemcitabine; among all patients, incidence was 2.7% (2.6-2.8) in cycle 1, 2.7% (2.6-2.8) in cycle 2, and 2.9% (2.9-3.0) in cycles thereafter. One-third of CIT episodes were managed in hospital, and for the subset of patients hospitalized with a first-listed diagnosis of CIT, mean length of stay was 4.6 (4.4-5.0) days and mean cost of inpatient care was $36,448 (32,332-41,331). Across cycles with CIT, mean cost of CIT-related care was $2179 (2029-2329), comprising $1024 (881-1167) for inpatient care and $1153 (1119-1187) for outpatient care. CONCLUSIONS: In this retrospective evaluation of cancer chemotherapy patients, CIT incidence was high, especially among patients receiving gemcitabine-based regimens, and the costs of CIT-related care were substantial. Accordingly, interventions aimed at identifying and targeting high-risk patients for preventative measures may yield substantial clinical and economic benefits.

Use and effectiveness of pegfilgrastim prophylaxis in US clinical practice:a retrospective observational study.

BACKGROUND: Febrile neutropenia (FN) is a serious complication of myelosuppressive chemotherapy. Clinical practice guidelines recommend routine prophylactic coverage with granulocyte colony-stimulating factor (G-CSF)-such as pegfilgrastim-for most patients receiving chemotherapy with an intermediate to high risk for FN. Patterns of pegfilgrastim prophylaxis during the chemotherapy course and associated FN risks in US clinical practice have not been well characterized. METHODS: A retrospective cohort design and data from two commercial healthcare claims repositories (01/2010-03/2016) and Medicare Claims Research Identifiable Files (01/2007-09/2015) were employed. Study population included patients who had non-metastatic breast cancer or non-Hodgkin's lymphoma and received intermediate/high-risk regimens. Pegfilgrastim prophylaxis use and FN incidence were ascertained in each chemotherapy cycle, and all cycles were pooled for analyses. Adjusted odds ratios for FN were estimated for patients who did versus did not receive pegfilgrastim prophylaxis in that cycle. RESULTS: Study population included 50,778 commercial patients who received 190,622 cycles of chemotherapy and 71,037 Medicare patients who received 271,944 cycles. In cycle 1, 33% of commercial patients and 28% of Medicare patients did not receive pegfilgrastim prophylaxis, and adjusted odds of FN were 2.6 (95% CI 2.3-2.8) and 1.6 (1.5-1.7), respectively, versus those who received pegfilgrastim prophylaxis. In cycle 2, 28% (commercial) and 26% (Medicare) did not receive pegfilgrastim prophylaxis; corresponding adjusted FN odds were comparably elevated (1.9 [1.6-2.2] and 1.6 [1.5-1.8]). Results in subsequent cycles were similar. Across all cycles, 15% of commercial patients and 23% of Medicare patients did not receive pegfilgrastim prophylaxis despite having FN in a prior cycle, and prior FN increased odds of subsequent FN by 2.1-2.4 times. CONCLUSIONS: Notwithstanding clinical practice guidelines, a large minority of patients did not receive G-CSF prophylaxis, and FN incidence was substantially higher among this subset of the population. Appropriate use of pegfilgrastim prophylaxis may reduce patient exposure to this potentially fatal but largely preventable complication of myelosuppressive chemotherapy.

Primary immune thrombocytopenia in US clinical practice: incidence and healthcare burden in first 12 months following diagnosis.

Introduction: Primary immune thrombocytopenia (ITP), an autoimmune disorder characterized by low platelet count, can lead to serious bleeding events. Little is known about the current epidemiology of ITP in the US, and even less is known about the current healthcare burden of ITP, especially in the 12-month period following ITP diagnosis.Method: We used a retrospective cohort design and data from two US private healthcare claims databases (2010-2016) to identify persons with evidence of newly diagnosed ITP. We weighted estimates of the annual incidence of ITP by age and sex to reflect the US population, and summarized healthcare utilization and expenditures (2016 US$) during the first 12 months after ITP diagnosis ("follow-up period").Results: Annual incidence of ITP in the US was 6.1 per 100,000 persons, higher among females versus males (6.7 vs. 5.5), and highest among children aged 0-4 years (8.1) and adults aged ≥65 years (13.7). Patients with ITP averaged 0.33 (95% CI: 0.32-0.35) hospitalizations and 15.3 (15.1-15.6) ambulatory encounters during the follow-up period; mean total healthcare expenditures during this period were $21,290 (20,502-22,031). Hospitalizations were more common during the first 3 months following diagnosis, and were twice as frequent among children versus adults; expenditures for ambulatory encounters were substantially higher for adults versus children aged 0-4 years.Conclusions: Our findings suggest that nearly 20,000 children and adults are newly diagnosed with ITP each year in the US, substantially higher than previously reported. Among patients requiring formal medical care, the economic burden during the first 12 months following diagnosis is high, with estimated US expenditures totaling over $400 million.

Bleeding and recurrent VTE with apixaban vs warfarin as outpatient treatment: time-course and subgroup analyses.

In the phase 3 trial Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy, apixaban was noninferior to enoxaparin, overlapped and followed by warfarin, in the treatment of venous thromboembolism (VTE) with significantly less bleeding; in a real-world evaluation, risks for bleeding and recurrent VTE were lower with apixaban vs warfarin plus parenteral anticoagulant (PAC) bridge therapy. The present study extends this research by comparing outcomes over time and within selected subgroups. A retrospective observational cohort design and 4 US private health care claims databases were used. Study population included patients who initiated outpatient treatment with apixaban or warfarin (plus PAC bridge therapy) for VTE. Major bleeding, clinically relevant nonmajor (CRNM) bleeding, and recurrent VTE were compared during the 180-day follow-up period, at selected follow-up time points (days 21, 90, 180), and within subgroups (pulmonary embolism [PE] with or without deep vein thrombosis [DVT], DVT only, provoked VTE, unprovoked VTE) using multivariable shared frailty models. Study population consisted of 20 561 apixaban patients and 35 080 warfarin patients; baseline characteristics were comparable. Overall, at selected follow-up time points, and within the aforementioned subgroups, adjusted risks were lower among apixaban vs warfarin patients: major bleeding, by 27% to 39%, CRNM bleeding, by 17% to 28%, and recurrent VTE, by 25% to 39% (all P ≤ .01). In this real-world study of VTE patients, risks of bleeding and recurrent VTE were lower among apixaban (vs warfarin) patients during the 180-day follow-up period, at selected follow-up time points, and within subgroups defined by index VTE episode.

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis: a retrospective evaluation using Medicare claims.

BACKGROUND: Two recent evaluations reported that many cancer chemotherapy patients discontinue pegfilgrastim prophylaxis (PP) following the first cycle, and that these patients have a higher subsequent risk of febrile neutropenia (FN). Such evidence is based principally on the experience of younger adults with private healthcare coverage, and the generalizability of results to elderly Medicare patients is unknown. METHODS: A matched-cohort design and data from the Medicare Claims Research Identifiable Files were employed. The source population comprised cancer patients aged ≥65 years who received chemotherapy with intermediate/high-risk for FN and first-cycle PP. From the source population, beginning with the second cycle, all patients who received PP in all previous cycles were identified. From this sub-set, patients who did not receive PP in the cycle of interest ("comparison patients") were matched to those who received PP in that cycle ("PP patients"); the same process was repeated for subsequent cycles. Odds ratios (OR) for FN (broad and narrow definitions) were estimated using generalized estimating equations. RESULTS: Among 77,616 elderly patients in the source population, 5.3% did not receive second-cycle PP and were matched to those who did. In cycle 2, FN odds were significantly higher among comparison patients vs PP patients when employing the broad definition (OR = 1.9, p < .001) and the narrow definition (OR = 2.1, p < .001). Results for subsequent cycles (broad definition: OR = 2.0, p < .001; narrow definition: OR = 2.1, p < .001) and for the last cycle (broad definition: OR = 1.4, p = .060; narrow definition: OR = 1.7, p = .055) were largely comparable. CONCLUSIONS: In this large-scale evaluation of elderly Medicare patients who received myelosuppressive chemotherapy and first-cycle PP in recent US clinical practice, FN risk was substantially lower among patients who continued to receive PP in subsequent cycles vs those who discontinued PP.

Risk of chemotherapy-induced febrile neutropenia with same-day versus next-day pegfilgrastim prophylaxis among patients aged ≥65 years: a retrospective evaluation using Medicare claims.

BACKGROUND: Two recent evaluations reported that risk of febrile neutropenia (FN) may be higher when pegfilgrastim prophylaxis (PP) is administered on same day as chemotherapy rather than per recommendation (1-3 days following chemotherapy). Such evidence is based largely on the experience of younger privately insured adults and may not be generalizable to older patients in US clinical practice. METHODS: A retrospective cohort design and data from Medicare Claims Research Identifiable Files (January 2008-September 2015) were employed. Patients were aged ≥65 years, had breast cancer or non-Hodgkin's lymphoma, received chemotherapy with intermediate/high risk for FN, and received PP in ≥1 cycle; cycles with PP were stratified based on administration day (same-day ["Day 0"] vs. 1-3 days following chemotherapy ["Days 1-3"]) and were pooled for analyses. Adjusted odds ratios (ORs) for FN during the cycle were estimated for patients who received PP on Day 0 versus Days 1-3. RESULTS: Study population included 65,003 patients who received PP in 261,184 cycles; in 5% of cycles, patients received PP on Day 0. Incidence proportion for FN in cycle 1 was 11.4% for Day 0 versus 8.4% for Days 1-3; adjusted OR was 1.4 (p < .001). Incidence proportion for FN when considering all cycles was 7.7% for Day 0 and 6.0% for Days 1-3; adjusted OR was 1.3 (p < .001). Adjusted ORs when considering all cycles and only inpatient FN episodes (1.3, p < .001) and the narrow definition for FN (1.5, p < .001) were similar. CONCLUSIONS: Among Medicare patients receiving chemotherapy and PP in US clinical practice, PP was administered before the recommended timing in 5% of cycles and FN incidence was significantly higher in these cycles. Along with prior research, study findings support recently updated US practice guidelines indicating that PP should be administered the day after chemotherapy.

Effectiveness and Safety of Apixaban versus Warfarin as Outpatient Treatment of Venous Thromboembolism in U.S. Clinical Practice.

In the AMPLIFY clinical trial, apixaban was non-inferior to warfarin plus subcutaneous enoxaparin bridge therapy in the treatment of acute venous thromboembolism (VTE) and was associated with significantly less bleeding. This study evaluated their comparative effectiveness and safety in routine clinical practice. A matched-cohort design and data from four U.S. private health care claims databases were employed. Study population comprised patients who initiated outpatient treatment with apixaban versus warfarin (plus parenteral anticoagulant bridge therapy) within 30 days of their initial VTE episode; apixaban and warfarin patients were matched on age, characteristics of VTE episode, study database and propensity score. Major bleeding, clinically relevant non-major (CRNM) bleeding and recurrent VTE during the 180-day (maximum) follow-up period were compared using shared frailty models. During mean follow-up of 143 days among apixaban patients (n = 17,878) and 152 days among warfarin patients (n = 17,878), incidence proportions for apixaban versus warfarin, respectively, were 1.7% versus 2.3% for major bleeding, 7.0% versus 9.4% for CRNM bleeding and 2.3% versus 2.9% for recurrent VTE. In shared frailty models, risks of major bleeding (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.64-0.87), CRNM bleeding (HR = 0.77, 95% CI = 0.71-0.83) and recurrent VTE (HR = 0.80, 95% CI = 0.70-0.91) were lower for apixaban versus warfarin. In this large-scale evaluation of VTE patients receiving outpatient treatment with apixaban or warfarin in U.S. clinical practice, risks of major bleeding, CRNM bleeding and recurrent VTE were significantly lower among patients who received apixaban.