Comparative analysis of persistence and remission with guselkumab versus secukinumab and ixekizumab in the United States.

Purpose: Real-world data comparing long-term performance of interleukin (IL)-23 and IL-17 inhibitors in psoriasis are limited. This study compared treatment persistence and remission among patients initiating guselkumab versus IL-17 inhibitors.Methods: Adults with psoriasis initiating guselkumab, secukinumab, or ixekizumab treatment (index date) were identified from Merative™ MarketScan® Research Databases (01/01/2016-10/31/2021). Persistence was defined as no index biologic supply gaps of twice the labeled maintenance dosing interval. Remission was defined using an exploratory approach as index biologic discontinuation for ≥6 months without psoriasis-related inpatient admissions and treatments.Results: There were 3516 and 6066 patients in the guselkumab versus secukinumab comparison, and 3805 and 4674 patients in guselkumab versus ixekizumab comparison. At 18 months, the guselkumab cohort demonstrated about twice the persistence rate as secukinumab (hazard ratio [HR] = 2.15; p < 0.001) and ixekizumab cohorts (HR = 1.77; p < 0.001). At 6 months after index biologic discontinuation, the guselkumab cohort was 31% and 40% more likely to achieve remission than secukinumab (rate ratio [RR] = 1.31; p < 0.001) and ixekizumab cohorts (RR = 1.40; p < 0.001).Conclusions: Guselkumab was associated with greater persistence and likelihood of remission than IL-17 inhibitors, indicating greater disease control and modification potential.

Real-World Maintenance Phase Persistence on Ustekinumab and Adalimumab in Ulcerative Colitis.

Purpose: To describe real-world persistence in bio-naïve and bio-experienced adults with ulcerative colitis (UC) treated with ustekinumab, a recently approved anti-interleukin 12/23 antibody, or adalimumab, an anti-TNF biologic. Methods: This is a descriptive, retrospective cohort study. Patients initiating ustekinumab or adalimumab (index date, between 10/21/2019 and 08/13/2021) were selected from the Komodo Health comprehensive dataset and stratified into bio-naïve and bio-experienced subgroups based on biologic use 12 months pre-index date. Endpoints evaluated at 12-months after maintenance phase start using Kaplan-Meier analysis included 1) persistence; 2) persistence while being corticosteroid-free (<14 consecutive days of corticosteroid supply after day 90 post-index); and, 3) persistence while on monotherapy (no immunomodulators/non-index biologics/advanced therapies). Results: Ustekinumab cohort included 778 patients (236 bio-naïve, 542 bio-experienced) and adalimumab cohort included 1693 patients (1517 bio-naive, 176 bio-experienced). At 12 months after maintenance phase start, 75.5% and 50.5% of bio-naïve patients persisted on ustekinumab and adalimumab and 72.3% and 56.9% of bio-experienced patients persisted on ustekinumab and adalimumab, respectively. Further, 55.1% and 38.2% of bio-naïve patients were persistent and corticosteroid-free with ustekinumab and adalimumab; 43.7% and 33.4% of bio-experienced patients were persistent and corticosteroid-free with ustekinumab and adalimumab, respectively. Moreover, 68.1% and 44.5% of bio-naïve patients were persistent and on monotherapy with ustekinumab and adalimumab; 61.6% and 47.9% of bio-experienced patients were persistent and on monotherapy with ustekinumab and adalimumab, respectively. Conclusion: At 12 months after maintenance phase start, patients with UC treated with ustekinumab had numerically higher persistence, including persistence while corticosteroid-free and persistence while on monotherapy, than patients treated with adalimumab.

Traumatic Life Events, Violence, and Obesity: A Cross-Sectional Study from 408 Patients Enrolled in a Bariatric Surgery Program.

INTRODUCTION: Obesity is a chronic disease that increases cardiovascular and metabolic morbidity and mortality, decreases quality of life, and increases health care costs. While the role of lifestyle behavioral factors in the development of obesity is well established, the role of traumatic life events, including violence, is unclear. The purpose of this study was to describe situations of traumatic life events reported by patients undergoing a bariatric surgery program, with a particular focus on sexual violence and its clinical correlates. METHODS: In this cross-sectional study, patients with grade II or III obesity, admitted to our digestive surgery department for bariatric surgery from August 01, 2019, to December 31, 2020, underwent a structured interview by a trained psychologist to describe the history of traumatic life events self-reported by the patients. The primary endpoint was the presence of a history of sexual violence (SV). Multivariate logistic regressions were applied to identify independent risk factors for SV. RESULTS: Of the 408 patients interviewed, 87.1% reported at least one traumatic life event and 33.1% reported having had an SV in the past. Female gender (aOR = 7.44, 95% confidence interval: 3.85-15.73; p < 0.001) and higher body mass index (1.05, 1.02-1.08; p = 0.002) were associated with an increased risk of SV. Male gender was associated with a higher risk of difficulties including sports cessation, depression, and work-related distress. CONCLUSION: In the context of obesity, psychosocial trauma is characterized by a high frequency and several gender specificities that must be taken into account in the management of these patients.

Characterizing the real-world economic burden of metastatic castration-sensitive prostate cancer in the United States.

AIMS: To describe healthcare resource utilization (HRU) and costs of patients with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: Linked data from Flatiron Metastatic PC Core Registry and Komodo's Healthcare Map were evaluated (01/2016-12/2021). Patients with chart-confirmed diagnoses for metastatic PC without confirmed castration resistance in Flatiron who initiated androgen deprivation therapy (ADT) monotherapy or advanced therapy for mCSPC in 2017 or later (index date) with a corresponding pharmacy or medical claim in Komodo Health were included. Advanced therapies considered were androgen-receptor signaling inhibitors, chemotherapies, estrogens, immunotherapies, poly ADP-ribose polymerase inhibitors, and radiopharmaceuticals. Patients with <12 months of continuous insurance eligibility before index were excluded. Per-patient-per-month (PPPM) all-cause and PC-related HRU and costs (medical and pharmacy; from a payer's perspective in 2022 $USD) were described in the 12-month baseline period and follow-up period (from the index date to castration resistance, end of continuous insurance eligibility, end of data availability, or death). RESULTS: Of 871 patients included (mean age: 70.6 years), 52% initiated ADT monotherapy as their index treatment without documented advanced therapy use. During baseline, 31% of patients had a PC-related inpatient admission and 94% had a PC-related outpatient visit; mean all-cause costs were $2551 PPPM and PC-related costs were $839 PPPM with $787 PPPM attributable to medical costs. Patients had a mean follow-up of 15 months, during which 38% had a PC-related inpatient admission and 98% had a PC-related outpatient visit; mean all-cause costs were $5950 PPPM with PC-related total costs of $4363 PPPM, including medical costs of $2012 PPPM. LIMITATIONS: All analyses were descriptive; statistical testing was not performed. Treatment effectiveness and clinical outcomes were not assessed. CONCLUSION: This real-world study demonstrated a significant economic burden in mCSPC patients, and a propensity to use ADT monotherapy in clinical practice despite the availability and guideline recommendations of advanced life-prolonging therapies.

Weight suppression at lowest weight as an indicator of eating disorder clinical severity: A retrospective cohort study.

OBJECTIVES: Weight suppression (WS) defines the difference between the highest weight in adulthood and the current weight. WS at lowest weight is the difference between the highest and the lowest ever weight. Weight rebound is the difference between the past lowest weight and current weight. The distinction in the capacities of WS, weight rebound, and WS at the lowest weight remains unclear regarding their efficacy in forecasting clinical endpoints. This study assessed the relationship between WS, WS at lowest weight and/or weight rebound and eating disorder (ED) clinical severity. METHODS: In this retrospective cohort study, adult participants were selected at the Outpatient Unit for multidisciplinary assessment of ED, Montpellier, France, between February 2012 and October 2014 and May 2017 and January 2020. ED clinical severity was evaluated using the Eating Disorder Examination Questionnaire (EDE-Q). RESULTS: The sample included 303 patients: 204 with anorexia nervosa (AN) and 99 with bulimia nervosa (BN). The EDE-Q total score was positively correlated with WS at lowest weight in patients with AN (Spearman's rho = 0.181, p = 0.015) and with BN (Spearman's rho = 0.377; p < 0.001). It was also positively correlated with weight rebound (Spearman's rho = 0.319; p = 0.003) in patients with BN. In the multivariate analysis, EDE-Q total score was associated with WS at lowest weight only in patients with BN (ß = 0.265; p = 0.03). CONCLUSION: WS at lowest weight seems to be a good measure of ED clinical severity. More research is needed for better understanding WS at lowest weight in assessment and treatment of patients with ED.

Cost of genetic testing, delayed care, and suboptimal treatment associated with polymerase chain reaction versus next-generation sequencing biomarker testing for genomic alterations in metastatic non-small cell lung cancer.

AIMS: To assess US payers' per-patient cost of testing associated with next-generation sequencing (NGS) versus polymerase chain reaction (PCR) biomarker testing strategies among patients with metastatic non-small cell lung cancer (mNSCLC), including costs of testing, delayed care, and suboptimal treatment initiation. METHODS: A decision tree model considered biomarker testing for genomic alterations using either NGS, sequential PCR testing, or hotspot panel PCR testing. Literature-based model inputs included time-to-test results, costs for testing/medical care, costs of delaying care, costs of immunotherapy [IO]/chemotherapy [CTX] initiation prior to receiving test results, and costs of suboptimal treatment initiation after test results (i.e. costs of first-line IO/CTX in patients with actionable mutations that were undetected by PCR that would have been identified with NGS). The proportion of patients testing positive for a targetable alteration, time to appropriate therapy initiation, and per-patient costs were estimated for NGS and PCR strategies combined. RESULTS: In a modeled cohort of 1,000,000 members (25% Medicare, 75% commercial), an estimated 1,119 had mNSCLC and received testing. The proportion of patients testing positive for a targetable alteration was 45.9% for NGS and 40.0% for PCR testing. Mean per-patient costs were lowest for NGS ($8,866) compared to PCR ($18,246), with lower delayed care costs of $1,301 for NGS compared to $3,228 for PCR, and lower costs of IO/CTX initiation prior to receiving test results (NGS: $2,298; PCR:$5,991). Cost savings, reaching $10,496,220 at the 1,000,000-member plan level, were driven by more rapid treatment with appropriate therapy for patients tested with NGS (2.1 weeks) compared to PCR strategies (5.2 weeks). LIMITATIONS: Model inputs/assumptions were based on published literature or expert opinion. CONCLUSIONS: NGS testing was associated with greater cost savings versus PCR, driven by more rapid results, shorter time to appropriate therapy initiation, and minimized use of inappropriate therapies while awaiting and after test results.

Real-world economic burden of metastatic castration-resistant prostate cancer before and after first-line therapy initiation.

AIMS: To describe healthcare costs of patients with metastatic castration-resistant prostate cancer (mCRPC) initiating first-line (1 L) therapies from a US payer perspective. METHODS: Patients initiating a Flatiron oncologist-defined 1 L mCRPC therapy (index date) on or after mCRPC diagnosis were identified from linked electronic medical records/claims data from the Flatiron Metastatic Prostate Cancer (PC) Core Registry and Komodo's Healthcare Map. Patients were excluded if they initiated a clinical trial drug in 1 L, had <12 months of insurance eligibility prior to index, or no claims in Komodo's Healthcare Map for the Flatiron oncologist-defined index therapy. All-cause and PC-related total costs per-patient-per-month (PPPM), including costs for services and procedures from medical claims (i.e. medical costs) and costs from pharmacy claims (i.e. pharmacy costs), were described in the 12-month baseline period before 1 L therapy initiation (including the baseline pre- and post- mCRPC progression periods) and during 1 L therapy (follow-up). RESULTS: Among 459 patients with mCRPC (mean age 70 years, 57% White, 16% Black, 45% commercially-insured, 43% Medicare Advantage-insured, and 12% Medicaid-insured), average baseline all-cause total costs (PPPM) were $4,576 ($4,166 pre-mCRPC progression, $8,278 post-mCRPC progression). Average baseline PC-related total costs were $2,935 ($2,537 pre-mCRPC progression, $6,661 post-mCRPC progression). During an average 1 L duration of 8.5 months, mean total costs were $13,746 (all-cause) and $12,061 (PC-related) PPPM. The cost increase following 1 L therapy initiation was driven by higher PC-related outpatient and pharmacy costs. PC-related medical costs PPPM increased from $1,504 during baseline to $5,585 following 1 L mCRPC therapy initiation. LIMITATIONS: All analyses were descriptive; statistical testing was not performed. CONCLUSION: Incremental costs of progression to mCRPC are significant, with the majority of costs driven by higher PC-related costs. Using contemporary data, this study highlights the importance of utilizing effective therapies that slow progression and reduce healthcare resource demands despite the initial investment in treatment costs.

Time to next treatment in patients with chronic lymphocytic leukemia initiating first-line ibrutinib or acalabrutinib.

Aim: To investigate real-world time to next treatment in patients with chronic lymphocytic leukemia initiating first-line (1L) ibrutinib or acalabrutinib. Materials & methods: US specialty pharmacy electronic medical records (21/11/2018-30/4/2022) were used; patients initiated 1L on/after 21/11/2019 (acalabrutinib approval). Results: Among 710 patients receiving ibrutinib, 5.9% initiated next treatment (mean time to initiation = 9.2 months); among 373 patients receiving acalabrutinib, 7.5% initiated next treatment (mean time to initiation = 5.9 months). Adjusting for baseline characteristics, acalabrutinib-treated patients were 89% more likely to initiate next treatment (hazard ratio = 1.89; p = 0.016). Conclusion: This study addresses a need for real-world comparative effectiveness between 1L ibrutinib and acalabrutinib and shows that next treatment (a clinically meaningful measure for real-world progression) occurred less frequently with 1L ibrutinib.

Ibrutinib and acalabrutinib are oral medications taken once-daily and twice-daily, respectively. They are recommended as initial treatment for chronic lymphocytic leukemia (CLL). The goal of this study was to compare the efficacy of these treatments as initial treatment for CLL. To meet this goal, real-world US specialty pharmacy electronic medical records between 11/21/2018­4/30/2022 were used. Patients treated with ibrutinib or acalabrutinib as initial treatment for CLL were studied. Treatment had to be started on or after the date of acalabrutinib approval for CLL (11/21/2019). Time to next treatment was used to estimate real-world disease progression. It was defined as the time from the initiation of initial treatment with ibrutinib or acalabrutinib to the initiation of a next treatment. Study results showed that patients were observed for a median of up to 1.5 years. Over this period, next treatment was more likely for acalabrutinib (7.5%) compared with ibrutinib (5.9%). After adjusting for differences in patient characteristics, next treatment was 89% more likely with acalabrutinib than ibrutinib. This study addresses a need to compare the effectiveness of initial treatment with ibrutinib and acalabrutinib in the real-world. It helps better contextualize results from clinical trial data and shows that next treatment occurred less frequently with ibrutinib.

Gastrointestinal manifestations in pediatric and adult patients with Rett syndrome: an analysis of US claims and physician survey data.

Aim: Patients with Rett syndrome (RTT) experience gastrointestinal (GI) manifestations. This study aimed to describe the prevalence of GI manifestations and the associated medical costs in patients with RTT in the USA. Patients & Methods: The study combined an insurance claims database analysis with a survey of 100 physicians experienced in RTT management. Results: GI manifestations affected 43.0% of 5940 patients, with increased prevalence in pediatric patients (45.6%) relative to adult patients (40.2%). Annualized mean medical cost of managing GI manifestations was $4473. Only 5.9-8.2% of neurologists and pediatricians ranked GI symptom management among the five most important treatment goals. Conclusion: Patients with RTT experience a high burden of GI manifestations, which translate to considerable medical costs. Importantly, the prevalence of GI manifestations was likely underestimated in this study, as only those symptoms which resulted in a healthcare encounter were captured.

Economic Burden of Delayed Diagnosis in Patients with Pulmonary Arterial Hypertension (PAH).

BACKGROUND: The aim of this study was to assess health care resource utilization (HRU) and costs associated with delayed pulmonary arterial hypertension (PAH) diagnosis in the United States. METHODS: Eligible adults with newly diagnosed PAH from Optum's de-identified Clinformatics® Data Mart Database (2016-2021) were assigned to mutually exclusive cohorts based on time between first PAH-related symptom and first PAH diagnosis (i.e., ≤12 months' delay, >12 to ≤24 months' delay, >24 months' delay). All-cause HRU and health care costs per patient per month (PPPM) were assessed during the first year following diagnosis and compared across cohorts using regression analysis adjusted for baseline covariates. Sensitivity analyses were conducted to assess outcomes during all available follow-up post-diagnosis. RESULTS: Among 538 patients (mean age: 65.6 years; 60.6% female), 60.8% had ≤12 months' delay, 23.4% had a delay of >12 to ≤24 months, and 15.8% had >24 months' delay. Compared with ≤12 months, delays of >12 to ≤24 months and >24 months were associated with increased hospitalizations (incidence rate ratio [95% confidence interval]: 1.40 [1.11-1.71] vs 1.71 [1.29-2.12]) and outpatient visits (1.17 [1.06-1.30] vs 1.26 [1.08-1.41]). Longer delays were also associated with more intensive care unit (ICU) stays and 30-day readmissions. Diagnosis delays translated into excess costs PPPM of US$3986 [1439-6436] for >12 to ≤24 months and US$5366 [2107-8524] for >24 months compared with ≤12 months' delay; increased hospitalization costs (US$3248 [1108-5135] and US$4048 [1401-6342], respectively) being the driver. Sensitivity analyses yielded similar trends. CONCLUSIONS: Delayed PAH diagnosis is associated with significant incremental economic burden post-diagnosis, driven by hospitalizations including ICU stays and 30-day readmissions, highlighting the need for increased awareness and a potential benefit of earlier screening.

Real-world clinical management of individuals with Rett syndrome: a physician survey.

BACKGROUND: Rett syndrome (RTT) is a severe neurodevelopmental disorder. Management strategies are heterogeneous with no clear definition of success. This study describes physician decision-making regarding diagnosis, therapeutic goals, and management strategies to better understand RTT clinical management in the US. METHODS: This study was conducted among practicing physicians, specifically neurologists and pediatricians in the US with experience treating ≥2 individuals with RTT, including ≥1 individuals within the past two years. In-depth interviews with five physicians informed survey development. A cross-sectional survey was then conducted among 100 physicians. RESULTS: Neurologists had treated more individuals with RTT (median: 12 vs. 5, p < 0.001) than pediatricians throughout their career and were more likely to report being "very comfortable" managing RTT (31 vs. 4%, p < 0.001). Among physicians with experience diagnosing RTT (93%), most evaluated symptoms (91%) or used genetic testing (86%) for RTT diagnoses; neurologists used the 2010 consensus diagnostic criteria more than pediatricians (54 vs. 29%; p = 0.012). Improving the quality of life (QOL) of individuals with RTT was the most important therapeutic goal among physicians, followed by improving caregivers' QOL. Most physicians used clinical practice guidelines to monitor the progress of individuals with RTT, although neurologists relied more on clinical scales than pediatricians. Among all physicians, the most commonly treated symptoms included behavioral issues, epilepsy/seizures, and feeding issues. Management strategies varied by symptom, with referral to appropriate specialists being common across symptoms. A large proportion of physicians (37%) identified the lack of novel therapies and reliance on symptom-specific management as an unmet need. CONCLUSION: Although most physicians had experience and were comfortable diagnosing and treating individuals with RTT, better education and support among pediatricians is warranted. Additionally, novel treatments that target multiple symptoms associated with RTT could reduce the burden and improve the QOL of individuals with RTT and their caregivers.

Effect of Nutritional Deprivation after Sleeve Gastrectomy on Bone Mass, Periostin, Sclerostin and Semaphorin 4D: A Two-Year Longitudinal Study.

Bariatric surgery induces bone loss, but the exact mechanisms by which this process occurs are not fully known. The aims of this 2-year longitudinal study were to (i) investigate the changes in areal bone mineral density (aBMD) and bone turnover markers following sleeve gastrectomy (SG) and (ii) determine the parameters associated with the aBMD variations. Bone turnover markers, sclerostin, periostin and semaphorin 4D were assessed before and 1, 12 and 24 months after SG, and aBMD was determined by DXA at baseline and after 12 and 24 months in 83 patients with obesity. Bone turnover increased from 1 month, peaked at 12 months and remained elevated at 24 months. Periostin and sclerostin presented only modest increases at 1 month, whereas semaphorin 4D showed increases only at 12 and 24 months. A significant aBMD decrease was observed only at total hip regions at 12 and 24 months. This demineralisation was mainly related to body weight loss. In summary, reduced aBMD was observed after SG in the hip region (mechanical-loading bone sites) due to an increase in bone turnover in favour of bone resorption. Periostin, sclerostin and semaphorin 4D levels varied after SG, showing different time lags, but contrary to weight loss, these biological parameters did not seem to be directly implicated in the skeletal deterioration.

Real-World Incidence of Adverse Clinical Outcomes Among People With Coronary Artery Disease and/or Peripheral Artery Disease in Relation to Vascular Risk in the United States.

Presence of polyvascular disease, diabetes, heart failure, or renal insufficiency in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD) are associated with increased risks of adverse events, including major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs). In this retrospective observational study using administrative claims data from Optum's deidentified Clinformatics Data Mart Database from January 2016 to September 2021, we described the incidence rates of MACEs, MALEs, and major thrombotic vascular events in patients with CAD or PAD stratified by the presence of risk factors (i.e., polyvascular disease, diabetes, heart failure, or renal insufficiency). A total of 1,435,241 patients (77% CAD and 34% PAD) met the inclusion and exclusion criteria. Patients with 0 risk factors were deemed the low-risk group (47%; n = 681,333) and patients with ≥1 risk factor were deemed the high-risk group (53%; n = 753,908). The mean age was 71.8 and 73.6 years, and 42% and 44% were female in the low- and high-risk groups, respectively. Compared with the low-risk group, the high-risk group had a 72% higher hazard of developing MACEs (adjusted hazard ratio 1.72, 95% confidence interval 1.70 to 1.74), 82% higher hazard of developing major thrombotic vascular events (1.82, 1.80 to 1.84), and 146% higher hazard of developing MALEs (2.46, 2.39 to 2.53) (all p <0.001). In conclusion, in patients with CAD or PAD, the presence of 1 or more risk factors was associated with higher risks of MACEs, MALEs, and major thrombotic vascular events, underscoring the need to improve management of underlying diseases in this population.

Real-World Treatment Patterns Among Patients with Connective Tissue Disorder-Related Pulmonary Arterial Hypertension in the United States: A Retrospective Claims-Based Analysis.

INTRODUCTION: Connective tissue disorders (CTDs) are the most frequent diseases associated with pulmonary arterial hypertension (PAH). Despite advances in treatment, the prognosis of CTD-related PAH remains poor. To help identify areas for improvement in the management of CTD-related PAH, this study assessed real-world PAH treatment patterns in this population in the US. METHODS: Eligible adult patients with PAH initiated on a PAH treatment (index date: 1st initiation date) were identified from Optum's de-identified Clinformatics® Data Mart Database (10/01/2015-09/30/2021) and categorized into mutually exclusive cohorts (CTD + PAH; PAH) based on the presence of CTD diagnosis claims. Treatment patterns were assessed from the index date to the earliest of death or end of continuous insurance eligibility, or data availability. Treatment persistence was assessed using Kaplan-Meier analysis. RESULTS: A total of 4751 patients were included (CTD + PAH: n = 728, mean follow-up of 18.8 months; PAH: n = 4023, mean follow-up of 19.6 months). For both cohorts, the most common first treatment regimens were sildenafil (CTD + PAH: 38.7%; PAH: 51.5%), tadalafil (10.0%; 9.4%), and macitentan (8.1%; 5.4%) monotherapy; these were also the most frequent agents included in any of the first 3 treatment regimens. Combination therapy was more frequent in the CTD + PAH versus PAH cohort (any regimen: 40.9% vs. 27.2%; 1st treatment regimen: 26.9% vs. 18.5%; 2nd: 52.8% vs. 42.0%; 3rd: 55.2% vs. 48.5%). Treatment persistence was similar across cohorts and the first three treatment regimens, with persistence rates ranging from 42.6 to 49.7% at 12 months. CONCLUSIONS: Treatment patterns were generally similar between the CTD + PAH and PAH cohorts, although combination therapy was more frequent in the CTD + PAH cohort. Both cohorts may benefit from broader use of all available PAH treatment classes, including combination therapy. Considering the life-threatening nature of PAH, our findings also highlight the need to address the low persistence rates with PAH therapies regardless of etiology.

Persistence and Dose Escalation During Maintenance Phase and Use of Nonbiologic Medications Among Patients With Ulcerative Colitis Initiated on Ustekinumab in the United States.

Background: Real-world data on treatment patterns among patients with ulcerative colitis (UC) initiated on ustekinumab are limited. Methods: Adults with UC initiated on ustekinumab (index date) between 10/18/2019 and 04/31/2022 were selected from a deidentified health insurance claims database (Symphony Health, an ICON plc Company, PatientSource). Persistence (no gaps in days of supply >120 days), persistence while being corticosteroid-free (no corticosteroid use for ≥14 days of supply after a 90-day grace period from index date) and dose escalation (≥2 consecutive subcutaneous claims ≥100% above daily maintenance dose) were described during the maintenance phase using Kaplan-Meier analysis. Nonbiologic treatments, among patients with ≥2 ustekinumab claims within 90 days post-index and ≥6 months of follow-up, were compared with logistic models 6 months post- versus pre-ustekinumab initiation. Results: 6565 patients on ustekinumab entered the maintenance phase. At month 12 of the maintenance phase, 72.0% (95% confidence interval [CI]: 70.1%-73.9%) were persistent, 50.8% (95% CI: 48.7%-52.9%) were persistent and corticosteroid-free, and 19.2% (95% CI: 17.3%-21.3%) of patients had dose escalation. In the 6 months post- versus pre-ustekinumab initiation, the odds of nonbiologic medication use assessed in 4147 patients were significantly lower: 57% lower odds for corticosteroid, 46% for 60 cumulative days of corticosteroid, 42% for 5-aminosalicylic acid, and 24% for immunomodulators (all P < .001). Conclusions: Most patients with UC reaching the maintenance phase on ustekinumab remained persistent after 12 months of maintenance therapy. Nonbiologic medication use post-ustekinumab initiation was significantly lower, notably for corticosteroids. Given the multiple complications associated with chronic corticosteroid use, this reduction can be seen as clinically relevant and informs treatment choice for patients with UC.

Real-world time to discontinuation of first-line venetoclax + obinutuzumab in chronic lymphocytic leukemia/small lymphocytic lymphoma.

OBJECTIVE: To evaluate the time to discontinuation (TTD) and baseline characteristics among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) treated with first-line (1L) venetoclax + obinutuzumab (VO) in the United States. METHODS: A nationwide electronic health record-derived database was used to select adults with CLL/SLL initiating a 1L venetoclax-based regimen between April 11, 2016-July 31, 2020. Study measures included TTD (defined as >120-day treatment gap or switching therapy) and baseline characteristics by discontinuation status. RESULTS: A total of 113 patients receiving 1L VO on/before July 31, 2020 were eligible for analysis (mean age: 65.9 years; 31.9% women). During the first 60 days post-treatment initiation, 3.5% had tumor lysis syndrome (TLS). The proportion of patients using corticosteroids, anti-hyperuricemics, and anti-emetics was higher during the first 60 days post-treatment initiation (100.0%, 78.8%, and 52.2%, respectively) than the period from day 61 onward (67.0%, 45.5%, and 33.9%, respectively). Mean (median) duration of active treatment was 11.6 (12.1) months; 16.8% discontinued treatment before completing 12 cycles, 68.1% completed ≥12 cycles (among which 29.9% completed ≥15 cycles), and 15.0% who did not discontinue treatment were censored before completing 12 cycles. Kaplan-Meier analysis showed that median TTD was 13.8 months. Relative to those completing ≥12 cycles, patients discontinuing treatment before completing the prescribed 12 cycles were older (70.4 vs. 65.1 years) and had poorer renal function (36.8% vs. 13.0% with creatinine clearance <60 mL/min). CONCLUSION: A small proportion of CLL/SLL patients who were older and had poorer baseline renal function discontinued 1L VO prior to completing 12 treatment cycles. Additionally, treatment utilization, including medications related to TLS mitigation and management, was more intense during the initiation phase of VO. Further research with longer follow-up to assess long-term outcomes of VO treatment after early discontinuation is warranted.

Unintended Consequences of Increased Out-of-Pocket Costs During Medicare Coverage Gap on Anticoagulant Discontinuation and Stroke.

INTRODUCTION: This study aims to assess the risk of direct oral anticoagulant (DOAC) discontinuation among Medicare beneficiaries with non-valvular atrial fibrillation (NVAF) who reach the Medicare coverage gap stratified by low-income subsidy (LIS) status and the impact of DOAC discontinuation on rates of stroke and systemic embolism (SE) among beneficiaries with increased out-of-pocket (OOP) costs due to not receiving LIS. METHODS: In this retrospective cohort study, Medicare claims data (2015-2020) were used to identify beneficiaries with NVAF who initiated rivaroxaban or apixaban and entered the coverage gap during ≥ 1 year. DOAC discontinuation rates during the coverage gap were stratified by receipt of Medicare Part D Low-Income Subsidy (LIS), a proxy for not experiencing increased OOP costs. Among non-LIS beneficiaries, incidence rates of stroke and SE during the subsequent 12 months were compared between beneficiaries who did and did not discontinue DOAC in the coverage gap. RESULTS: Among 303,695 beneficiaries, mean age was 77.3 years, and 28% received LIS. After adjusting for baseline differences, non-LIS beneficiaries (N = 218,838) had 78% higher risk of discontinuing DOAC during the coverage gap vs. LIS recipients (adjusted hazard ratio [aHR], 1.78; 95% CI [1.73, 1.82]). Among non-LIS beneficiaries, DOAC discontinuation during coverage gap (N = 91,397; 34%) was associated with 14% higher risk of experiencing stroke and SE during the subsequent 12 months (aHR, 1.14; 95% CI [1.08, 1.20]). CONCLUSION: Increased OOP costs during Medicare coverage gap were associated with higher risk of DOAC discontinuation, which in turn was associated with higher risk of stroke and SE among beneficiaries with NVAF.

Ischemic stroke and systemic embolism among patients with non-valvular atrial fibrillation who abandon oral anticoagulant therapy.

OBJECTIVES: To compare the risk of stroke and systemic embolism (SE) among patients with nonvalvular atrial fibrillation (NVAF) who abandoned their first direct oral anticoagulant (DOAC) fill ("abandoners") relative to patients who continued DOACs beyond the first fill ("continuers"). METHODS: In this retrospective longitudinal study, adults with NVAF prescribed DOACs were selected from Symphony Health, an ICON plc Company, PatientSource, 1 April 2017 to 31 October 2020. A 90-day landmark period following the first DOAC fill was used to classify patients as abandoners or continuers. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. Time to ischemic stroke/SE was described and compared between cohorts using weighted Kaplan-Meier and Cox proportional hazard models from the end of the landmark period until end of clinical activity or data. RESULTS: After weighting, 200,398 and 211,352 patients comprised the abandoner and continuer cohorts, respectively. The mean duration of follow-up was 14.9 and 15.7 months, respectively. At 12 months of follow-up, the probability of ischemic stroke/SE was 1.34% in the abandoner cohort and 1.00% in the continuer cohort; the risk of ischemic stroke/SE was 35% higher in the abandoner versus continuer cohort (hazard ratio [95% confidence interval] = 1.35 [1.20, 1.51]; p < 0.0001). CONCLUSIONS: Patients with NVAF who abandoned the first DOAC fill had significantly higher risk of ischemic stroke/SE compared to patients who continued therapy beyond the first fill. There is an unmet need for better access to DOACs so that the long-term risk of poor outcomes may be minimized.

Real-World Comparison of First-Line Treatment Adherence Between Single-Agent Ibrutinib and Acalabrutinib in Patients with Chronic Lymphocytic Leukemia.

Purpose: Increased dosing frequency adversely affects treatment adherence and outcomes in chronic diseases; however, such data related to treatment adherence is lacking in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). This study compared adherence between patients treated with ibrutinib (once-daily) versus acalabrutinib (twice-daily) as first-line (1L) therapy for CLL/SLL. Patients and Methods: Specialty pharmacy electronic medical records were used to identify adults with CLL/SLL initiating 1L ibrutinib or acalabrutinib between 01/01/2018 and 11/30/2020. Adherence was measured by the proportion of days covered (PDC) and medication possession ratio (MPR) and was compared between cohorts using odds ratios (ORs) obtained from logistic regression models adjusted for baseline characteristics. Results: Between 01/01/2018 and 11/30/2020, 1374 and 140 patients initiated ibrutinib and acalabrutinib, respectively. Based on PDC/MPR ≥80%, patients treated with once-daily ibrutinib were more likely to be adherent than those treated with twice-daily acalabrutinib (OR ranges: PDC: 1.04-1.76; MPR: 1.03-1.58). At 6 months, patients on ibrutinib had a 58-76% higher likelihood of staying adherent compared to patients on acalabrutinib (PDC: 75.9% for ibrutinib vs 63.6% for acalabrutinib, OR: 1.76, P=0.008; MPR: 76.8% vs 66.9%, OR: 1.58, P=0.036) with a similar trend noted for the entire line of treatment (LOT) (PDC: 53.0% vs 41.4%, OR: 1.53, P=0.021; MPR: 58.7% vs 47.1%, OR: 1.50, P=0.027). Conclusion: In this real-world analysis, CLL/SLL patients initiating 1L once-daily ibrutinib had >50% higher treatment adherence than those initiating twice-daily acalabrutinib during their LOT. Given the importance of sustained adherence for disease control in CLL/SLL, dosing frequency may be an important consideration for patients and physicians.