Real-world effectiveness of voxelotor for treating sickle cell disease in the US: a large claims data analysis.

BACKGROUND: Sickle cell disease (SCD) is a genetic disease that impacts patients' quality of life, healthcare costs, and life expectancy. Elevated sickle hemoglobin (HbS), which readily polymerizes, causes red blood cell sickling, leading to chronic hemolytic anemia and complications often requiring hospitalization and transfusions. In 2019, voxelotor, which inhibits HbS polymerization, was approved for SCD treatment. OBJECTIVES: This study uses real-world evidence to assess voxelotor's effectiveness in SCD patients in typical clinical practice from 2019 to 2021 using a national medical claims database (N = 3128). RESULTS: After initiating voxelotor, 60.8% of patients with available hemoglobin (Hb) laboratory data (n = 74) showed a Hb increase >1 g/dL. Mean transfusion rate per patient-year dropped 52% in patients with ≥1 transfusion before treatment (n = 190). In patients with ≥1 of the corresponding events (n = 1065), decreases were observed in mean vaso-occlusive crisis (VOC) frequency (-23%); mean VOC-related hospitalizations and length of stay (LOS) time (-34% and -30%, respectively); mean all-cause hospitalization and LOS time (-37% and -23%, respectively); outpatient visits (-10%); iron chelation use (-46%); and prescribed opioids (-13%). CONCLUSION: These data align with randomized controlled trial results showing voxelotor improvements and support that voxelotor may lower transfusion and VOC rates in clinical practice.

Quality-Adjusted Survival with Ribociclib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Postmenopausal Women with HR±HER2- Advanced Breast Cancer in the MONALEESA-3 Trial.

BACKGROUND: MONALEESA-3 demonstrated an overall survival (OS) benefit for ribociclib plus fulvestrant (R+F) in postmenopausal women with hormone receptor (HR) positive, HER2 negative advanced breast cancer (ABC). This study estimated quality-adjusted (QA) survival outcomes for patients receiving R+F vs. placebo (P)+F in MONALEESA-3. METHODS: Kaplan-Meier OS was partitioned into health states: (1) toxicity (TOX)=time spent with grade 3 -4 adverse events before progression (DP); (2) progression (PROG)=time between DP and death; and (3) time without symptoms or toxicity (TWiST)=time not in TOX or PROG. QA time was calculated by combining estimated mean time in each health state with treatment-group specific health-state utility values estimated using EQ-5D-5L questionnaire. Outcomes included QA progression-free survival (QAPFS), QAOS, and QA TWiST (Q-TWiST). Q-TWiST was calculated with health-state utility values for TOX and PROG defined relative to TWiST. RESULTS: Mean PFS and OS were significantly greater with R+F vs. P+F (difference 0.56 and 0.19 years). Mean time in TOX and TWiST were greater with R+F; mean time in PROG was greater with P+F. QAPFS was 0.45 years (95% CI 0.27 -0.63) greater with R+F than P+F (P <.001). QAOS was numerically greater with R+F vs. P+F (0.16 years, 95% CI 0.07 -0.45, P = .0569). Q-TWiST was 0.23 years greater with R+F (95% CI 0.07 -0.45, P = .0069). In a sensitivity analysis using an estimate of disutility for PROG, the difference in QAOS was 0.23 years (95% CI 0.08 -0.41, P = .0022). CONCLUSION: R+F in postmenopausal women with HR+/HER2- ABC improves QAPFS, resulting in clinically important improvements in Q-TWiST and may improve QAOS.

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.

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.

Use of colony-stimulating factor primary prophylaxis and incidence of febrile neutropenia from 2010 to 2016: a longitudinal assessment.

BACKGROUND: Guidelines recommend primary prophylactic use of colony-stimulating factor (PP-CSF) when risk of febrile neutropenia (FN) - based on chemotherapy and patient risk factors - is high. Whether and how PP-CSF use may have changed over time (e.g. due to guideline revisions, increasing use of myelosuppressive regimens, controversy regarding inappropriate CSF use), and whether there has been a concomitant change in the incidence of FN, is unknown. METHODS: A retrospective cohort design and data from two US healthcare claims repositories were employed. The study population included patients who had non-metastatic cancer of the breast, colon/rectum, lung or ovaries, or non-Hodgkin's lymphoma (NHL), and who received myelosuppressive chemotherapy regimens with an intermediate/high risk for FN. For each patient, the first cycle of the first course was characterized in terms of PP-CSF use and FN episodes. Crude incidence proportions for PP-CSF and FN during the first cycle were estimated by calendar quarter (2010-2016); multivariable logistic regression models were used to estimate quarter-specific adjusted mean probabilities of FN by PP-CSF use. RESULTS: The study population totaled 142,730 patients with breast cancer (61%), colorectal cancer (14%), NHL (11%), ovarian cancer (10%) or lung cancer (5%). PP-CSF use increased from 52% in 1Q2010 to 58% in 4Q2016; pegfilgrastim was the most commonly used agent (>96% across quarters). PP-CSF administration on the same day as chemotherapy ranged from 8 to 11% until 1Q2015, and increased to 64% by 4Q2016. Adjusted incidence proportions for FN in the first chemotherapy cycle ranged from 2.7% (95% CI: 2.3-3.0) to 3.7% (95% CI: 3.1-4.3) among those who did not receive PP-CSF, and was 2.6% (95% CI: 2.5-2.7) across quarters among those who received PP-CSF. CONCLUSIONS: Although the use of PP-CSF is commonplace in current US clinical practice, underutilization in cancer patients receiving chemotherapy regimens with an intermediate/high risk for FN may still be an issue. Use of same-day PP-CSF increased markedly from the end of 2015, although this finding reflects (at least in part) increased uptake of pegfilgrastim delivered via an on-body injector as well as the recent change in clinical practice guidelines. Overall, patients receiving PP-CSF appear to have a lower risk of FN during the first cycle of chemotherapy.

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.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.