Real-world effectiveness of elexacaftor/tezacaftor/ivacaftor on the burden of illness in adolescents and adults with cystic fibrosis.

Background: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and efficacious in people with cystic fibrosis (CF) aged ≥2 years. Here, we describe results from an observational study assessing change in burden of illness following initiating ELX/TEZ/IVA in real-world settings. Methods: This US-based, multicenter, observational study used data from electronic medical records to evaluate real-world burden of illness before and after ELX/TEZ/IVA initiation in people with CF aged ≥12 years heterozygous for F508del and a minimal function mutation (F/MF) or an uncharacterized CFTR mutation. Endpoints included absolute change from baseline in percent predicted forced expiratory volume in 1 s (ppFEV1), body mass index (BMI) and BMI-for-age z-score, glycated hemoglobin (HbA1c), and numbers of pulmonary exacerbations (PEx). Results: Overall, 206 people with CF were enrolled (mean [SD] age 22.5 [11.1] years; 192 [93.2%] with F/MF genotype). Mean follow-up was 15.6 (SD, 1.6) months. Improvements in ppFEV1 (7.3 [95% CI: 5.7, 8.8] percentage points) were observed from baseline through follow-up. Increases in BMI (1.40 [95% CI: 1.07, 1.77] kg/m2) and BMI-for-age z-score (0.14 [95% CI: 0.00, 0.28]) were also observed from baseline at 12 months. The estimated annualized rate of any PEx was 1.31 at baseline and 0.61 over follow-up (rate ratio 0.47 [95% CI: 0.39, 0.55]), with annualized rates of PEx requiring antibiotics and hospitalizations of 0.55 and 0.88 in the baseline period and 0.12 and 0.36 over follow-up (rate ratios 0.22 [95% CI: 0.15, 0.31] and 0.41 [95% CI: 0.32, 0.51]), respectively. Absolute change in HbA1c was -0.22 (95% CI: -0.38, -0.06) from baseline through follow-up. Conclusions: ELX/TEZ/IVA treatment was associated with improved lung function, increased BMI, reduced frequency of PEx, and improved (i.e., reduced) HbA1c. These results confirm the broad clinical benefits of ELX/TEZ/IVA seen in clinical trials and show the potential for ELX/TEZ/IVA to improve markers of glucose metabolism.

Reduction in healthcare resource use through 24 months following sinus surgery with steroid-eluting implants in chronic rhinosinusitis patients with and without nasal polyps: a real-world study.

OBJECTIVE: To investigate the impact of steroid-eluting implants after endoscopic sinus surgery (ESS) on health care resource use (HCRU) in chronic rhinosinusitis patients with (CRSwNP) and without (CRSsNP) nasal polyps. METHODS: This retrospective, observational cohort study using real-world evidence data included adult patients with CRS who underwent ESS in 2015-2019 with at least 24 months of data before and after ESS. Patients who received implants were matched to patients who did not based on a propensity score developed using baseline characteristics and NP status. HCRU was compared between cohorts within each CRSwNP and CRSsNP subgroup using chi-square tests (binary variables). RESULTS: The implant cohort in the CRSwNP subgroup had fewer all-cause outpatient (90.0% vs. 93.9%, p < .001) and all-cause otolaryngology (64.3% vs. 76.4%, p < .001) visits as well as fewer endoscopy (40.5% vs. 47.4%, p = .005) and debridement (48.8% vs. 55.6%, p = .007) procedures than the non-implant cohort. The implant cohort in the CRSsNP subgroup had fewer all-cause outpatient (88.9% vs. 94.2%, p < .001) and all-cause otolaryngology (53.5% vs. 74.4%, p < .001) visits as well as fewer endoscopy (31.8% vs. 41.7%, p < .001) and debridement (36.7% vs. 53.4%, p <.001) procedures than the non-implant cohort. Revision sinus surgery was reduced in the implant cohort in both subgroups, and reached statistical significance in the CRSwNP subgroup (3.8% vs. 6.0%, p = .039) but not in the CRSsNP subgroup (3.6% vs. 4.2%, p = .539). CONCLUSIONS: Overall, patients receiving implants had lower HCRU for 24 months after sinus surgery independent of nasal polyp status, and revision surgery was reduced in CRSwNP patients. These findings provide additional evidence that long-term reductions in HCRU may be achieved with steroid-eluting implant use during sinus surgery.What is known on this topicPatients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a disproportionately higher burden of disease and consume greater healthcare resources than chronic rhinosinusitis patients without nasal polyps (CRSsNP).CRSwNP patients represent approximately 30% of CRS patients who undergo surgery, but their clinical course is disproportionally complicated by disease recurrence and revision surgery.Steroid-eluting sinus implants have been shown in clinical trials to improve short-term postoperative outcomes after endoscopic sinus surgery (ESS) in CRS patients in general.A recent real-world evidence study reported that steroid-eluting sinus implants following ESS were associated with a reduction in HCRU in CRS patients followed for 18 months, but the impact of implants on HCRU in CRSwNP and CRSsNP patients separately remains unknown. What this study addsIn this observational study, reduced HCRU was observed in CRSwNP and CRSsNP patients who receive steroid-eluting sinus implants.Use of implants in CRSwNP and CRSsNP patients was associated with a significant reduction in healthcare visits (all-cause outpatient, all-cause otolaryngology), and sinus procedures (endoscopy, debridement).Revision surgery was significantly reduced in the implant cohort of CRSwNP patients and trended lower in the implant cohort of CRSsNP patients.Use of implants had no significant impact on all-cause ER/urgent care visits or sinus-related imaging.

Clinical and Economic Benefit of Achieving Disease Control in Psoriatic Arthritis and Ankylosing Spondylitis: A Retrospective Analysis from the OM1 Registry.

BACKGROUND: There is limited evidence on the clinical and economic benefit of achieving disease control in psoriatic arthritis (PsA) and ankylosing spondylitis (AS), thus we aimed to assess the impact of disease control on healthcare resource use (HCRU) and direct medical costs among US patients with PsA or AS over 1 year. METHODS: Data were derived from the US OM1 PsA/AS registries (PsA: 1/2013-12/2020; AS: 01/2013-4/2021) and the Optum Insight Clinformatics® Data Mart to identify adult patients with PsA or AS. Two cohorts were created: with disease control and without disease control. Disease control was defined as modified Disease Activity Index for Psoriatic Arthritis (DAPSA28) ≤ 4 for PsA and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 4 for AS. Outcomes were all-cause inpatient, outpatient, and emergency department (ED) visits and associated costs over a 1-year follow-up period. Mean costs per person per year (PPPY) were assessed descriptively and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were estimated for the likelihood of HCRU by logistic regression. RESULTS: The study included 1235 PsA (with disease control: N = 217; without: N = 1018) and 581 AS patients (with disease control: N = 342; without: N = 239). Patients without disease control were more likely to have an inpatient (aOR [95% CI]; PsA: 3.0 [0.9, 10.1]; AS: 7.7 [2.3, 25.1]) or ED (PsA: 1.6 [0.6, 4.2]; AS: 3.5 [1.5, 8.3]) visit than those with disease control. Those without disease control, vs. those with disease control, had greater PPPY costs associated with inpatient (PsA: $1550 vs. $443), outpatient (PsA: $1789 vs. $1327; AS: $2498 vs. $2023), and ED (PsA: $114 vs. $57; AS: $316 vs. $50) visits. CONCLUSIONS: Findings from this study demonstrate lower disease activity among patients with PsA and AS is associated with less HCRU and lower costs over the following year.

Real-world evidence analysis of the impact of steroid-eluting implants on healthcare resource use among chronic rhinosinusitis patients undergoing sinus surgery.

OBJECTIVE: To compare healthcare resource use (HCRU) in patients undergoing sinus surgery with or without steroid-eluting sinus implants. METHODS: A retrospective, observational cohort study using real-world evidence data (OM1, Inc, Boston, MA, USA) was conducted on adult patients with chronic rhinosinusitis (CRS) with or without nasal polyps who underwent endoscopic sinus surgery between 2014 and 2019 and had at least 18 months of data both before and after surgery. Patients receiving implants ("implant cohort") were matched to patients who did not receive implants ("non-implant cohort") based on a propensity score developed using baseline characteristics. Chi-square for binary variables and analysis of variance tests for continuous variables were applied to compare HCRU measures. RESULTS: Comparison of the implant (N = 1983) and non-implant (N = 1983) cohorts during the 18-month follow-up period demonstrated significantly lower HCRU in those receiving implants, including all-cause outpatient visits (94.3% vs. 96.6%, p < .001), all-cause otolaryngologist visits (47.3% vs. 59.6%, p < .001) and all cause ER/urgent care visits (9.2% vs. 11.8%, p = .007), as well as sinus-related endoscopies (39.1% vs. 43.8%, p = .003). Although not statistically significant, fewer patients in the implant cohort had undergone repeat surgeries (4.6% vs. 5.3%, p = .273). CONCLUSION: Patients with steroid-eluting sinus implants had lower HCRU over a post-operative period of 18 months. These findings support the contention that reductions in HCRU may be achieved using steroid-eluting implants during sinus surgery.What is known on this topicChronic rhinosinusitis (CRS) causes severe symptoms that lead to poor quality of life.Endoscopic sinus surgery (ESS) is 76-98% effective in improving CRS patients' symptoms.Surgical outcomes can be compromised in the immediate post-operative period by scarring, adhesion formation, and early polyp recurrence.Oral and topical corticosteroid therapy has become integral to the maintenance of successful surgical outcomes, the management of post-operative scarring and edema, and the prevention of nasal polyp recurrence.Steroid-eluting sinus implants have been shown in clinical trials to improve postoperative outcomes after ESS by delivering localized, sustained release of corticosteroids directly onto inflamed sinus tissue.What this study addsThis observational study is one of the first to use real-world evidence to assess the effect of steroid-eluting sinus implants on healthcare resource use (HCRU) in patients with chronic rhinosinusitis who underwent sinus surgery with or without implants.Use of implants significantly reduced HCRU, including all-cause outpatient visits (94.3% vs 96.6%, p < .001), all-cause otolaryngologist visits (47.3% vs 59.6%, p < .001), and all-cause ER/urgent care visits (9.2% vs 11.8%, p = .007), as well as sinus endoscopy (39.1% vs 43.8%, p = .003).Use of implants had no significant effect on sinus procedures such as debridement and polypectomy, as well as sinus-related imaging such as CT, MRI, and x-ray.

A Fully Magnetically Levitated Left Ventricular Assist Device - Final Report.

BACKGROUND: In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device. METHODS: We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years. RESULTS: This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axial-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (relative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 for superiority). Pump replacement was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P<0.001). The numbers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, a fully magnetically levitated centrifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.).

Comprehensive Analysis of Stroke in the Long-Term Cohort of the MOMENTUM 3 Study.

BACKGROUND: The MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) has demonstrated that the HeartMate 3 (HM3) pump is associated with reduced strokes compared with the HeartMate II (HMII) device. We now perform a comprehensive analysis of stroke events to evaluate their longitudinal occurrence, clinical correlates, patterns, and impact on outcome across the 2-year duration of support. METHODS: MOMENTUM 3 is a randomized controlled trial of the HM3 centrifugal-flow pump versus the HMII axial-flow pump in patients with advanced heart failure, regardless of the intended goal of support (bridge to transplantation or destination therapy). Baseline and postimplantation clinical correlates of stroke events were assessed with multivariable analyses. Longitudinal patterns, including device association, type of stroke (hemorrhagic versus ischemic), changing severity of impairment assessed with the modified Rankin Scale (disabling [modified Rankin Scale score >3] versus nondisabling [modified Rankin Scale score ≤3]) over time, and association with outcome, were determined. RESULTS: In 361 patients with the intended implant (189 HM3 and 172 HMII), 65 strokes (40 ischemic strokes and 25 hemorrhagic strokes) occurred in 52 patients at a median of 131 (range, 1-733) days. No difference in stroke rate was noted between 0 and 180 days of follow-up between devices. However, stroke incidence in the long-term period (181-730 days after left ventricular assist device) was 3.3 times lower for the HM3 group (HM3: 0.04 versus HMII: 0.13 events per patient-year; odds ratio, 0.23; 95% CI, 0.08-0.63; P=0.01). Treatment with the HM3 pump was the only independent predictor of lower stroke events. We found no direct association of blood pressure or antithrombotic regimens with observed stroke rates. A stroke event significantly lowered 2-year postimplantation survival regardless of subtype or initial severity of neurological impairment compared with patients without a stroke (43±12% for hemorrhagic stroke, 57±9% for ischemic stroke, 51±11% for disabling, and 51±11% for nondisabling compared with 85±2% 2-year survival for patients without stroke). CONCLUSIONS: The HM3 pump is associated with a marked reduction in stroke rates compared with the HMII device, with benefits observed in the long-term period (>6 months). The occurrence of stroke of any type (hemorrhagic and ischemic) or of any functional severity (disabling and nondisabling) is predictive of a poor 2-year clinical outcome. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02224755.