Risk of chemotherapy-induced febrile neutropenia by day of pegfilgrastim prophylaxis in US clinical practice from 2010 to 2015

<p><b>Objective:</b> Pegfilgrastim prophylaxis (PP) is recommended 1–3 days following administration of chemotherapy during the cycle. Some patients, however, receive PP before or after the recommended timing. While evidence suggests that risk of febrile neutropenia (FN) may be lower when PP is administered per recommendation, such evidence is based on older data. We undertook a new study to compare FN risk between patients who received PP on the last day of chemotherapy (“day 0”) or 4–5 days following chemotherapy (“days 4–5”), versus 1–3 days following chemotherapy (“days 1–3”), using recent data from US clinical practice.</p> <p><b>Methods:</b> A retrospective cohort design and data from two US private healthcare claims repositories (2010–2016) were employed. Patients received intermediate/high-risk chemotherapy regimens for solid tumors or non-Hodgkin’s lymphoma, and PP in ≥1 cycle; all cycles with PP were pooled for analyses. Adjusted odds ratios (OR) for FN during the cycle were estimated for patients who received PP on day 0 or days 4–5, vs. days 1–3, using generalized estimating equations.</p> <p><b>Results:</b> The study population included 53,814 patients who received PP in 217,273 cycles; in 9% of cycles, patients received PP on day 0 (8%) or days 4–5 (<1%). Odds of FN in cycle 1 were significantly higher among patients receiving PP on day 0 (OR: 1.4 [95% CI: 1.2–1.7]) or days 4–5 (1.9 [1.2–3.0]), vs. days 1–3, in that cycle. Results for subsequent cycles of chemotherapy were comparable to those for the first cycle.</p> <p><b>Conclusions:</b> In this large-scale retrospective evaluation of cancer chemotherapy patients receiving PP in recent US clinical practice, PP was administered before or after the recommended timing in 9% of cycles. FN incidence was significantly higher in these cycles providing additional real-world evidence that PP should be administered the day after chemotherapy in alignment with recently updated US practice guidelines.</p

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis based on real-world data from 2010 to 2015

<p><b>Objective:</b> Evidence suggests that not all cancer chemotherapy patients who receive first-cycle pegfilgrastim prophylaxis (PP) continue to receive it in later cycles, and that these patients may be subsequently at higher risk of febrile neutropenia (FN). Available evidence, however, may not be reflective of current clinical practice. We undertook an evaluation to estimate the odds of FN, beginning with second chemotherapy cycle, among patients who received PP in that cycle and all previous cycles versus those who received PP in all previous cycles only, using recent real-world data.</p> <p><b>Methods:</b> A matched-cohort design and data from two US healthcare claims repositories (2010–2015) were employed. The source population comprised cancer patients who received intermediate/high-risk chemotherapy 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 subset, 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 (ORs) for FN (broad and narrow definitions) were estimated using generalized estimating equations.</p> <p><b>Results:</b> Among 47,254 patients in the source population, 9% did not receive second-cycle PP and were matched to those who did. FN odds in cycle 2 were significantly higher among comparison patients versus PP patients (OR [broad definition]: 1.7, <i>p</i> < .001); OR [narrow definition]: 4.3, <i>p</i> < .001). Results for subsequent cycles and for the last cycle, respectively, were comparable (OR [range, broad definition]: 1.6 to 3.1, <i>p</i> < .001 for all; OR [range, narrow definition]: 2.7 to 11.8, <i>p</i> < .001 for all).</p> <p><b>Conclusions:</b> In this real-world evaluation of cancer chemotherapy patients who received first-cycle PP, FN risk was substantially higher among patients who did not receive PP in subsequent cycles versus those who continued PP.</p

Risk of exacerbation following pneumonia in adults with heart failure or chronic obstructive pulmonary disease

<div><p>Background</p><p>Recent evidence demonstrates increased short-term risk of cardiac complications and respiratory failure among patients with heart failure (HF) and chronic obstructive pulmonary disease (COPD), respectively, concurrent with an episode of community-acquired pneumonia (CAP). We evaluated patients with pre-existing HF or COPD, beginning 30 days after CAP diagnosis, to determine if CAP had a prolonged impact on their underlying comorbidity.</p><p>Methods</p><p>A retrospective matched-cohort design using US healthcare claims was employed. In each month of accrual, patients with HF or COPD who developed CAP (“CAP patients”) were matched (1:1, without replacement, on demographic and clinical profiles) to patients with HF or COPD who did not develop CAP (“comparison patients”). All patients were aged ≥40 years, and were pneumonia free during prior 1-year period. Exacerbation beginning 30 days after the CAP diagnosis and for the subsequent 1-year period were compared between CAP and comparison patients.</p><p>Findings</p><p>38,010 (4·6%) HF patients and 48,703 (5·9%) COPD patients experienced a new CAP episode requiring hospitalization or outpatient care only, and were matched to comparison patients. In the HF subset, CAP patients were 47·2% more likely to experience an exacerbation vs patients without CAP (17·8% vs. 12·1%; p<0·001); in the COPD subset, CAP patients were 42·3% more likely to experience an exacerbation (16·2% vs. 11·4%; p<0·001).</p><p>Conclusions</p><p>Our data provide evidence that CAP foreshadows a prolonged increase in risk of exacerbation of underlying HF or COPD in adults, and suggests a potential benefit to CAP prevention strategies.</p></div

Cumulative percentage of hospitalized pneumonia patients and matched comparison patients who experienced an HF/COPD-related exacerbation*.

<p>CAP: Community-acquired pneumonia; COPD: chronic obstructive pulmonary disease; HF: heart failure. Exacerbation: Hospitalization with principal diagnosis of condition of interest, or emergency department visit with diagnosis of condition of interest in any position. *Patients identified between 1/2010 and 5/2013 within Truven Health Analytics MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits Databases. †Follow-up began 30 days after CAP diagnosis and ended 12 months later. ‡All comparisons p<0.001.</p

Cost-effectiveness of an autoantibody test (<i>Early</i>CDT-Lung) as an aid to early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules

<div><p>Objective</p><p>Patients who have incidentally detected pulmonary nodules and an estimated intermediate risk (5–60%) of lung cancer frequently are followed via computed tomography (CT) surveillance to detect nodule growth, despite guidelines for a more aggressive diagnostic strategy. We examined the cost-effectiveness of an autoantibody test (AABT)—Early Cancer Detection Test-Lung (EarlyCDT-Lung^TM)—as an aid to early diagnosis of lung cancer among such patients.</p><p>Methods</p><p>We developed a decision-analytic model to evaluate use of the AABT versus CT surveillance alone. In the model, patients with a positive AABT—because they are at substantially enhanced risk of lung cancer—are assumed to go directly to biopsy, resulting in diagnosis of lung cancer in earlier stages than under current guidelines (a beneficial stage shift). Patients with a negative AABT, and those scheduled for CT surveillance alone, are assumed to have periodic CT screenings to detect rapid growth and thus to have their lung cancers diagnosed—on average—at more advanced stages.</p><p>Results</p><p>Among 1,000 patients who have incidentally detected nodules 8–30 mm, have an intermediate-risk of lung cancer, and are evaluated by CT surveillance alone, 95 (9.5%) are assumed to have lung cancer (local, 73.6%; regional, 22.0%; distant, 4.4%). With use of the AABT set at a sensitivity/specificity of 41%/93% (stage shift = 10.8%), although expected costs would be higher by $949,442 ($949 per person), life years would be higher by 53 (0.05 per person), resulting in a cost per life-year gained of $18,029 and a cost per quality-adjusted life year (QALY) gained of$24,330. With use of the AABT set at a sensitivity/specificity of 28%/98% (stage shift = 7.4%), corresponding cost-effectiveness ratios would be $18,454 and$24,833.</p><p>Conclusions</p><p>Under our base-case assumptions, and reasonable variations thereof, using AABT as an aid in the early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules who are estimated to be at intermediate risk of lung cancer and are scheduled for CT surveillance alone is likely to be a cost-effective use of healthcare resources.</p></div

Population, disease, and strategy characteristics for patients who have incidentally detected pulmonary nodules, are at intermediate risk, and were scheduled for CT surveillance alone.

<p>Population, disease, and strategy characteristics for patients who have incidentally detected pulmonary nodules, are at intermediate risk, and were scheduled for CT surveillance alone.</p

Characteristics of hospitalized CAP patients and matched comparison patients in heart failure and chronic obstructive pulmonary disease populations^*.

<p>Characteristics of hospitalized CAP patients and matched comparison patients in heart failure and chronic obstructive pulmonary disease populations^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184877#t001fn002" target="_blank">*</a>}.</p

Additional file 1: of Rates and costs of invasive pneumococcal disease and pneumonia in persons with underlying medical conditions

Supplemental Material-Operational Algorithms and Additional Results. (DOCX 2446 kb

Health state utilities and costs for patients who have incidentally detected pulmonary nodules, are at intermediate risk, and were scheduled for CT surveillance alone.

<p>Health state utilities and costs for patients who have incidentally detected pulmonary nodules, are at intermediate risk, and were scheduled for CT surveillance alone.</p

Outcomes (discounted) with use of AABT versus CT surveillance alone for early diagnosis of lung cancer in patients who have incidentally detected pulmonary nodules, are at intermediate risk, and were scheduled for CT surveillance alone^*.

<p>Outcomes (discounted) with use of AABT versus CT surveillance alone for early diagnosis of lung cancer in patients who have incidentally detected pulmonary nodules, are at intermediate risk, and were scheduled for CT surveillance alone^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0197826#t003fn002" target="_blank">*</a>}.</p