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.

Treatment Patterns, Acute Healthcare Resource Use, and Costs of Patients with Treatment-Resistant Depression Completing Induction Phase of Esketamine in the United States.

BACKGROUND: This study aimed to understand treatment patterns, acute healthcare use, and cost patterns among adults with treatment-resistant depression (TRD) who completed induction treatment with esketamine nasal spray in the United States (US). Per label, induction is defined as administration twice a week for 4 weeks, after which maintenance is started on a weekly basis for 4 weeks, and thereafter, patients are treated weekly or bimonthly. METHODS: Adults with one or more esketamine claim (index date) on or after March 5, 2019 were selected from Optum's de-identified Clinformatics® Data Mart Database (January 2016-June 2022). Before the index date, patients had evidence of TRD and ≥ 12 months of continuous insurance eligibility (baseline period). Patients with eight or more esketamine treatment sessions were included in the main cohort. A subgroup included patients with one or more baseline mental health (MH)-related inpatient (IP) admission or emergency department (ED) visit (i.e., prior acute healthcare users). Treatment patterns were described during the follow-up period (index date until earliest of end of insurance eligibility or data); acute healthcare (i.e., IP and ED) resource use and costs (2021 US dollars) were reported during the baseline and follow-up periods. RESULTS: Of the 322 patients in the main cohort, 111 comprised the subgroup of prior acute healthcare users. During the follow-up period, mean time from index date to eighth esketamine session was 73.2 days in the main cohort and 78.8 days in the subgroup (per label, 28 days). Further, 75.2% of the main cohort and 73.9% of the subgroup completed four or more esketamine maintenance sessions following induction. In the main cohort, mean all-cause acute healthcare costs per patient per month (PPPM) decreased from baseline ($837) to follow-up ($770). Similar reductions were observed for mean MH-related acute healthcare costs PPPM (baseline $648, follow-up $577). In the subgroup, mean all-cause acute healthcare costs PPPM also decreased (baseline $2323, follow-up $1423), driven by mean MH-related acute healthcare costs PPPM (baseline $1880, follow-up $1139). Mean all-cause acute healthcare use per ten patients per month remained largely stable from baseline to follow-up in the main cohort (IP days: baseline 2.24, follow-up 2.13; ED visits: baseline 1.33, follow-up 1.45) and decreased in the subgroup (IP days: baseline 6.38, follow-up 4.56; ED visits: baseline 2.58, follow-up 2.41). Trends in mean MH-related acute healthcare use were similar. CONCLUSION: Patients generally required more time than label recommendation to complete esketamine induction treatment, and most went on to have 12 or more esketamine sessions. Completion of induction treatment correlated with reductions in mean all-cause and MH-related acute healthcare costs. Larger reductions were seen in the subgroup of prior acute healthcare users.

Economic burden of generalized myasthenia gravis (MG) in the United States and the impact of common comorbidities and acute MG-events.

BACKGROUND: This study assessed the incremental healthcare costs and resource utilization (HRU) associated with generalized myasthenia gravis (gMG), as well as variability in these outcomes among patients with gMG and common comorbidities and acute MG-related events. METHODS: Adults with gMG and without MG were identified from a large US database (2017-2021). The index date was the first MG diagnosis (gMG cohort) or random date (non-MG cohort). Cohorts were propensity score matched 1:1. The gMG cohort included subgroups of patients with a 12-month pre-index (baseline) cardiometabolic or psychiatric comorbidity, or a post-index MG exacerbation/crisis. Monthly healthcare costs (2021 USD) and HRU were compared post-index between gMG and non-MG cohorts. RESULTS: The gMG and matched non-MG cohorts each contained 2,739 patients. Mean incremental healthcare costs associated with MG were $4,155 (gMG: $5,567; non-MG: $1,411), with differences driven by incremental inpatient costs of $2,166 (gMG: $2,617; non-MG: $452); all p < 0.001. The gMG versus non-MG cohort had 4.36 times more inpatient admissions and 2.26 times more outpatient visits; all p < 0.001. Among patients with gMG in cardiometabolic (n = 1,859), psychiatric (n = 1,308), and exacerbation/crisis (n = 419) subgroups, mean monthly healthcare costs were $6,660, $7,443, and $17,330, respectively. CONCLUSIONS: gMG is associated with substantial incremental costs and HRU, with inpatient costs driving the total incremental costs. Costs increased by 20% and 34% among patients with cardiometabolic and psychiatric conditions, respectively, and over three times among those with acute MG-related events. gMG is a complex disease requiring management of comorbidities and treatment options that can prevent acute symptomatic events.

Generalized myasthenia gravis (gMG) is a rare long-standing condition that affects the junctions between nerves and muscles, causing them to be weak. In a serious case, the diaphragm ­ a muscle that helps with breathing ­ becomes so weak that a patient will need a machine to breathe for them. This is called MG exacerbation or crisis. In this study, we used a large insurance database in the United States to look at how much money healthcare payers paid for gMG patients on average and what healthcare resources patients with gMG used. We compared these findings with patients without gMG. Also, among patients with gMG, we reported these findings specifically for patients who also had heart, blood, or blood vessel disease; patients who had a mental illness; and patients who had MG exacerbation or crisis later on. We found that patients with gMG used $5,567 per month on average ($4,155 more than patients without gMG), mostly from overnight hospital stays. Patients with gMG also had four times more overnight hospital stays and two times more hospital day visits when we compared them to patients without gMG. Patients with gMG and other health conditions used even more money and resources per month. Patients with MG exacerbation or crisis used $17,330 per month on average. Our results showed that gMG led to higher healthcare cost and resource use. In order to reduce cost and resources, doctors also need to control for other health conditions as they treat patients with gMG, and to prevent patients from having MG exacerbation or crisis later on.

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.

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.

Burden of chronic corticosteroid use among patients with ulcerative colitis initiated on targeted treatment or conventional therapy in the United States.

BACKGROUND: Chronic corticosteroid use is common in ulcerative colitis (UC); however, real-world evidence of its burden to the health care system is limited. OBJECTIVE: To quantify chronic corticosteroid use burden in UC. METHODS: Adults with UC initiated on targeted treatments (ie, biologics and advanced/small molecule therapies) or conventional therapy (index date) were selected from a deidentified US insurance claims database (January 1, 2004, to September 30, 2021). Targeted treatments and conventional therapy initiators were stratified into chronic (>90 days corticosteroid use 12 months post-index [landmark]) and nonchronic corticosteroid users. Patient characteristics 12 months pre-index were balanced with inverse probability of treatment weighting. Health care resource use, costs (US$ 2021), and corticosteroid-related complications were compared in the 12 months post-landmark. RESULTS: Targeted treatment initiators included 1,886 chronic and 1,911 nonchronic corticosteroid users; conventional therapy initiators included 4,980 chronic and 5,199 nonchronic users. Chronic vs nonchronic users had 94% more inpatient days and 16% more outpatient visits among targeted treatment initiators, and 135% more inpatient days and 30% more outpatient visits among conventional therapy initiators (all P < 0.01). Mean all-cause total costs per patient per year were $73,491 for chronic vs $58,884 for nonchronic users ($14,607 higher; P < 0.01) for targeted treatment initiators, and $39,335 for chronic vs $21,271 for nonchronic users ($18,065 higher; P < 0.01) for conventional therapy initiators. Odds of infection and bone loss were 14% and 113% higher, respectively, in chronic vs nonchronic users among targeted treatment initiators and 29% and 47% higher in chronic vs nonchronic users among conventional therapy initiators (all P < .01). CONCLUSIONS: The results of this study suggest that chronic corticosteroid use is associated with substantial clinical and economic burden and may indicate unmet needs in the management of UC progression.

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.

Economic and clinical burden of chronic corticosteroid use in patients with Crohn[apos]s disease initiated on biologic or conventional therapies in the US: A retrospective claims study.

BACKGROUND: Chronic corticosteroid (CS) use is associated with complications, but estimates of the economic and clinical burden in patients with Crohn's disease (CD) are lacking. OBJECTIVE: To estimate the burden of chronic CS use in CD in the United States in terms of health care resource utilization (HRU), health care costs, and CS-related complications. METHODS: This was a retrospective study of adults with CD initiated on biologics or conventional therapies (index date). Patients from a deidentified insurance claims database (2004-2021) were classified as chronic CS users (>90 days of CS use) or nonchronic CS users based on a 12-month landmark period starting on the index date. Patient baseline characteristics were balanced, and outcomes (HRU, costs [2021 US dollars], and CS-related complications) 12 months after the landmark period were compared between CS groups using regressions with nonparametric bootstrap resampling to estimate confidence intervals and P values. RESULTS: Biologic initiators (mean age: 44 years, 55% female) included 3366 chronic and 3401 nonchronic CS users; conventional therapy initiators (mean age: 51 years, 59% female) included 3657 chronic and 3727 nonchronic CS users. Compared with nonchronic users, chronic users had significantly more inpatient days and outpatient visits (biologic initiators: 37% and 24% more, respectively; conventional therapy initiators: 36% and 17%, respectively; all P<0.05). Chronic users also had significantly higher mean all-cause total costs per-patient-per year (biologic: $72,967 vs. $63,100, mean cost difference [MCD] = $9867; conventional therapy: $40,144 vs. $26,426, MCD = $13,718; all P<0.001), as well as higher odds of infection (biologic: 14% higher; conventional therapy: 20% higher) and bone loss (63% and 41%, respectively) (all P<0.05). CONCLUSION: Chronic CS use in patients with CD is associated with a significant economic and clinical burden including higher HRU, health care costs, and prevalence of complications, suggesting unmet needs in the clinical management of this population.

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.

Long-term persistence and other treatment patterns among bio-naïve patients with Crohn's disease treated with ustekinumab or adalimumab.

OBJECTIVE: To estimate long-term persistence among bio-naïve patients with CD initiated on ustekinumab or adalimumab. METHODS: Adults with CD initiating ustekinumab or adalimumab (index date, between September 23, 2016 and August 1, 2019) were sampled from the IBM MarketScan Commercial Database. Patients without CD-indicated biologics (bio-naïve) and with no diagnoses for other autoimmune diseases 12 months pre-index date (baseline) were included. Cohorts were balanced on baseline characteristics with inverse probability of treatment weighting. Persistence was defined as the absence of therapy exposure gaps >120 days (ustekinumab) or >60 (adalimumab) between days of supply. Composite endpoints were persistence and being corticosteroid-free (no corticosteroids >14 days of supply after day 90 post-index) and persistence while on monotherapy (no immunomodulators/non-index biologics). Persistence was analyzed using Kaplan-Meier and Cox's models. RESULTS: Ustekinumab and adalimumab cohorts included 671 and 2,975 patients. At 12 months post-index, ustekinumab patients were significantly more persistent (hazard ratio [HR] = 1.60; 95% confidence interval [CI] = 1.33-1.93), persistent while on monotherapy (HR = 1.43; 95% CI = 1.24-1.65), and trended toward being more persistent and corticosteroid-free (HR = 1.14; 95% CI = 0.99-1.30) vs adalimumab. At 24 months post-index, ustekinumab patients were significantly more persistent (HR = 1.66; 95% CI = 1.40-1.97), persistent while on monotherapy (HR = 1.44; 95% CI = 1.26-1.64), and persistent and corticosteroid-free (HR = 1.15; 95% CI = 1.01-1.31) vs adalimumab. CONCLUSIONS: Bio-naïve patients with CD initiated on ustekinumab demonstrated significantly more persistence than patients initiated on adalimumab at 12 and 24 months of treatment. Long-term persistence is a measure of a drug's real-world performance and findings may aid clinical decision-making.

Choosing a treatment on which a patient can stay over a long period of time is key for the successful management of chronic conditions such as Crohn's disease. Information on whether and how long patients stay on treatment can help physicians make the right therapeutic choice. This study examined whether adults with Crohn's disease, who have not previously taken biologics, stay on treatment longer when given the biologic ustekinumab or adalimumab. At 12 and 24 months after starting the treatment, a larger proportion of patients were still using ustekinumab compared with adalimumab. The proportion of patients using the biologic without immunomodulators or other biologics was also higher with ustekinumab. The results suggest that patients without previous biologic experience stay on treatment longer with ustekinumab than with adalimumab.

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.

Persistence and other treatment patterns among bio-experienced patients with Crohn's disease initiated on ustekinumab or adalimumab.

BACKGROUND: Real-world data on persistence on ustekinumab and adalimumab among bio-experienced patients with Crohn's disease (CD) are limited. OBJECTIVE: To compare treatment persistence and describe switching, restart, and dose titration among bio-experienced patients with CD initiated on ustekinumab or adalimumab. METHODS: IBM MarketScan Commercial Database was used to identify bio-experienced adults with CD who were assigned to either the ustekinumab or adalimumab cohort based on the agent first initiated (index date) after September 23, 2016. Cohorts were balanced using inverse probability of treatment weights-average treatment effect on treated. Persistence on index agent (absence of exposure gap > 120 days for ustekinumab or > 60 days for adalimumab), persistence while corticosteroid-free, and persistence while receiving monotherapy were assessed at 12 months after index date and compared between cohorts using weighted Kaplan-Meier and Cox proportional hazards model analyses. RESULTS: Among 903 patients in the ustekinumab cohort and 525 patients in the adalimumab cohort, baseline characteristics were balanced after weighting. At 12 months post-index, ustekinumab was associated with higher persistence (80.1% vs 64.6%; hazard ratio = 2.02 [95% CI = 1.60-2.56]; P < 0.001) and persistence while receiving monotherapy (51.6% vs 40.0%; 1.51 [1.28-1.78]; P < 0.001) vs adalimumab. Persistence while corticosteroid-free was similar in the ustekinumab vs adalimumab cohort (50.1% vs 48.2%; 1.19 [1.00-1.41]; P = 0.0516). CONCLUSIONS: This retrospective real-world study demonstrated that among bio-experienced patients with CD, initiation of ustekinumab was associated with better persistence at 12 months of follow-up, including persistence while receiving monotherapy, compared with adalimumab. DISCLOSURES: This study was funded by Janssen Scientific Affairs, LLC. Drs Zhao, Ding, and Kachroo are employees of Janssen Scientific Affairs, LLC, and stockholders of Johnson & Johnson. Dr Manceur, Mr Lefebvre, Ms Zhdanava, and Mr Pilon are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study and article. Mr Holiday was an employee of Analysis Group, Inc., at the time of study conduct.

Access and real-world use patterns of esketamine nasal spray among patients with treatment-resistant depression covered by private or public insurance.

OBJECTIVE: To describe access and real-world use patterns of esketamine nasal spray among adults with treatment-resistant depression (TRD) with private or public insurance. METHODS: Adults with ≥1 claim for esketamine nasal spray were selected from Clarivate's Real World Data product (January 2016-March 2021). Patients with evidence of TRD initiating esketamine (index date) after 05 March 2019 were included. Esketamine access, as measured by pharmacy claim approval rate for each treatment session, and use patterns were described post-index (follow-up period). RESULTS: Among 535 patients with pharmacy claims for esketamine nasal spray (mean age 49.1 years; 65.4% females), 534 had the first esketamine claim being a pharmacy claim, of which 34.6% were approved, 46.3% were rejected, and 19.1% were abandoned. Main reasons for rejection included "claim not covered by plan" (57.1%), "claim errors" (52.6%), and "prior authorization required" (22.7%). The approval rate increased to 85.2% by the second esketamine treatment session. A total of 273 patients initiated esketamine (mean age 49.3 years; 66.3% females). Patients had a mean ± standard deviation (SD) of 11.8 ± 13.3 esketamine sessions over a mean ± SD of 11.8 ± 6.4 months; 47.6% of patients completed ≥8 sessions (i.e. the number of sessions in induction phase) over a mean ± SD of 80.1 ± 71.9 days (per label, 28 days); 48 (17.6%) patients completed induction per label, and among them 93.8% continued treatment. CONCLUSIONS: Initial access to esketamine nasal spray may be hindered by prior authorization or claim filing errors. Among patients who initiated esketamine, treatment compliance generally deviates from label recommendations; yet, most of those who received induction per label successfully transition to maintenance with esketamine.

Esketamine nasal spray is a novel therapy for treatment-resistant depression (TRD). In the United States, insurance plans often regulate access to esketamine. Additionally, for patients, it may be challenging to comply to the treatment schedule, because patients must receive esketamine in a certified treatment center, be monitored for 2 h for potential side effects, and they cannot drive until the next day. This real-world study used insurance claims data and found that patients with TRD had difficulties accessing esketamine. Among those with access, esketamine use patterns were suboptimal.

Persistence Among Patients with Crohn Disease Previously Treated with an Anti-tumor Necrosis Factor Inhibitor and Switching or Cycling to Another Biologic Agent.

PURPOSE: Nonresponse to an anti-tumor necrosis factor (TNF) agent in patients with Crohn disease (CD) is often managed by either a switch to a different class of biologic (ie, ustekinumab, vedolizumab) or by cycling to another anti-TNF agent (ie, adalimumab, infliximab, certolizumab pegol). Persistence after a switch to a different biologic class or after cycling within the anti-TNF class was assessed in patients with nonresponse to an anti-TNF agent. METHODS: Adults with CD who discontinued from an anti-TNF agent and either switched to a different class of biologic (ie, anti-interleukin/integrin; the switching cohort) or cycled within the anti-TNF class (the cycling cohort) between September 23, 2016, and August 1, 2019, were selected from a commercial database. The index date was defined as the date of the first claim of the subsequent-line biologic (index biologic) after an anti-TNF. The switching and cycling cohorts were balanced with regard to baseline characteristics, using inverse probability of treatment weights-average treatment effect (IPTW-ATE). Persistence with the index biologic was defined as consistent use with no gaps of >120 days (ustekinumab, vedolizumab, infliximab) or of >60 days (adalimumab, certolizumab pegol) in biologic supply. Composite end points were persistence while being corticosteroid-free (defined as no use of corticosteroids with ≥14 days of supply after day 90 post-index) and persistence while on monotherapy (no immunomodulators/nonindex biologics). Weighted Kaplan-Meier and Cox models were used to assess outcomes at 12 months post-index. FINDINGS: There were 444 patients in the weighted switching cohort (mean age, 40.4 years; 56.3% female) and 441 in the weighted cycling cohort (mean age, 39.5 years; 58.4% female). At 12 months post-index, the rate of persistence with the index biologic was 75.7% in the switching cohort compared to 67.5% in the cycling cohort (log-rank P = 0.023); the rate of persistence while on monotherapy was 58.2% compared to 44.2%, respectively (log-rank P < 0.001). The rate of persistence was 44% greater in the switching compared to that in the cycling cohort (hazard ratio [HR] = 1.44; 95% CI, 1.11-1.88; P = 0.007); the rate of persistence while on monotherapy was 56% greater in the switching cohort (HR = 1.56; 95% CI, 1.28-1.90; P < 0.001). The between-cohort difference in persistence while being corticosteroid-free was not statistically significant (HR = 1.08; 95% CI, 0.89-1.32; P = 0.426). IMPLICATIONS: Patients with CD who switched to a different biologic class were more persistent than were patients who cycled to another anti-TNF agent. These findings may be useful for physicians when considering the treatment of patients who have experienced nonresponse or loss of response to the first-line anti-TNF agent.

Continuity of care among patients newly initiated on second-generation oral or long-acting injectable antipsychotics during a schizophrenia-related inpatient stay.

BACKGROUND: Maintaining continuity of care after schizophrenia-related hospitalization is challenging for patients and healthcare providers and systems. Prior evidence suggests that second-generation long-acting injectable antipsychotics (SGLAIs) may reduce the risk of treatment nonadherence and readmission versus oral atypical antipsychotics (OAAs). Therefore, quality measures were compared between patients initiated on SGLAIs and OAAs in the United States. METHODS: Adults newly initiated on an SGLAI or OAA during a schizophrenia-related inpatient stay were identified in HealthVerity databases (01/2015-12/2020); the index date was the hospital discharge date. Patients had continuous health insurance coverage for pharmacy and medical services for 6 months pre-admission and post-discharge from the inpatient stay and ≥1 pharmacy or medical claim (i.e. treatment as indicated by the observed insurance claims) for an antipsychotic other than the index SGLAI or OAA in the 6 months pre-admission. Antipsychotic use and adherence, and schizophrenia-related readmissions and outpatient visits were compared during the 6-month period post-discharge. Characteristics between cohorts were balanced using inverse probability weights. RESULTS: Post-discharge, only 36.9% and 40.7% of weighted SGLAI (N = 466) and OAA (N = 517) patients had ≥1 pharmacy or medical claim for the antipsychotic initiated during the inpatient stay, among whom SGLAI patients were 4.4 times more likely to be adherent to that antipsychotic compared to OAA patients (p < .001). Additionally, SGLAI patients were 2.3 and 3.0 times more likely to have a pharmacy or medical claim for and be adherent to any antipsychotic relative to OAA patients (including index antipsychotic; all p < .001). Within 7 and 30 days post-discharge, 1.7% and 13.0% of SGLAI patients and 4.1% and 12.6% of OAA patients had a readmission. Further, SGLAI patients were 51% more likely to have an outpatient visit compared to OAA patients (p = .044). CONCLUSIONS: Less than half of patients initiated on antipsychotics during a schizophrenia-related inpatient stay continued the same treatment post-discharge. However, SGLAI patients were more likely to be adherent to the initiated antipsychotic and to have an outpatient visit, which may suggest improved continuity of care post-discharge relative to OAA patients.

A Cross-Sectional Study of Patient Out-of-Pocket Costs for Antipsychotics Among Medicaid Beneficiaries with Schizophrenia.

BACKGROUND: Patient affordability is an important nonclinical consideration for treatment access among patients with schizophrenia. OBJECTIVE: This study evaluated and measured out-of-pocket (OOP) costs for antipsychotics (APs) among Medicaid beneficiaries with schizophrenia. METHODS: Adults with a schizophrenia diagnosis, ≥ 1 AP claim, and continuous Medicaid eligibility were identified in the MarketScan® Medicaid Database (1 January 2018-31 December 2018). OOP AP pharmacy costs ($US 2019) were normalized for a 30-day supply. Results were descriptively reported by route of administration [ROA; orals (OAPs), long-acting injectables (LAIs)], generic/branded status within ROAs, and dosing schedule within LAIs. The proportion of total (pharmacy and medical) OOP costs AP-attributable was described. RESULTS: In 2018, 48,656 Medicaid beneficiaries with schizophrenia were identified (mean age 46.7 years, 41.1% female, 43.4% Black). Mean annual total OOP costs were $59.97, $6.65 of which was AP attributable. Overall, 39.2%, 38.3%, and 42.3% of beneficiaries with a corresponding claim had OOP costs > $0 for any AP, OAP, and LAI, respectively. Mean OOP costs per patient per 30-day claim (PPPC) were $0.64 for OAPs and $0.86 for LAIs. By LAI dosing schedule, mean OOP costs PPPC were $0.95, $0.90, $0.57, and $0.39 for twice-monthly, monthly, once-every-2-months, and once-every-3-months LAIs, respectively. Across ROAs and generic/branded status, projected OOP AP costs per-patient-per-year for beneficiaries assumed fully adherent ranged from $4.52 to $13.70, representing < 25% of total OOP costs. CONCLUSION: OOP AP costs for Medicaid beneficiaries represented a small fraction of total OOP costs. LAIs with longer dosing schedules had numerically lower mean OOP costs, which were lowest for once-every-3-months LAIs among all APs.

Esketamine nasal spray for major depressive disorder with acute suicidal ideation or behavior: description of treatment access, utilization, and claims-based outcomes in the United States.

AIMS: To describe real-world esketamine nasal spray access and use as well as healthcare resource use (HRU) and costs among adults with evidence of major depressive disorder (MDD) with suicidal ideation or behavior (MDSI). METHODS: Adults with ≥1 claim for esketamine nasal spray and evidence of MDSI 12 months before/on the date of esketamine initiation (index date) were selected from Clarivate's Real World Data product (01/2016-03/2021). Patients initiated esketamine on/after 03/05/2019 (esketamine approval for treatment-resistant depression; later approved for MDSI on 08/05/2020) were included in the overall cohort. Esketamine access (measured as approved/abandoned/rejected claims) and use were described post-index; HRU and healthcare costs (2021 USD) were described over 6 months pre- and post-index. RESULTS: Among 269 patients in the overall cohort with esketamine pharmacy claims, 46.8% had the first pharmacy claim approved, 38.7% had it rejected, and 14.5% abandoned their claim; 169 patients were initiated on esketamine in the overall cohort (mean age 40.9 years, 62.1% female); 45.0% had ≥8 esketamine treatment sessions (recommended per label) with a mean [median] of 85.0 [58.5] days from index to 8th session (per label 28 days). Among 115 patients with ≥6 months of data post-index, in the 6-month pre- and post-index, respectively, 37.4 and 19.1% had all-cause inpatient admissions, 42.6 and 33.9% had emergency department visits, 92.2 and 81.7% had outpatient visits; mean ± standard deviation all-cause monthly total healthcare costs were $8,371±$15,792 and $6,486±$7,614, respectively. LIMITATIONS: This was a descriptive claims-based analysis; no formal statistical comparisons were performed due to limited sample size as data covered up to 24 months of esketamine use in the US clinical setting. CONCLUSIONS: Nearly half of patients experience access issues with first esketamine nasal spray treatment session. All-cause HRU and healthcare costs trend lower in the 6 months after relative to 6 months before esketamine initiation.

Major depressive disorder (MDD), or clinical depression, can sometimes be accompanied by preoccupation with suicide along with suicidal behavior. Patients diagnosed with MDD with suicidal ideation or behavior (MDSI) can vary in their reactions to this condition, and some never seek treatment. This study investigated treatment patterns in real-world clinics of a recently approved nasal spray therapy, esketamine, which helps improve depressive symptoms in patients with MDSI. The study results highlight challenges related to esketamine treatment access, particularly for the first treatment session. Still, healthcare resource utilization and healthcare costs trended lower following treatment initiation with esketamine in MDSI, suggesting the potential benefits of esketamine in mitigating the clinical and economic burden of MDSI among those who gain access to the drug. Streamlining the approval process by health plan providers to remove hindrances related to compliance with plan requirements may ensure more timely access to esketamine for MDSI.

Venous thromboembolism recurrence among one-and-done direct oral anticoagulant users: a retrospective longitudinal study.

BACKGROUND: Direct oral anticoagulants (DOACs) are the American Society of Hematology guideline-recommended treatment for venous thromboembolism (VTE) in the United States (US). AIM: To compare risk of VTE recurrence between patients who, following the first fill, discontinued ("one-and-done") versus those who continued ("continuers") DOACs. METHOD: Open source US insurance claims data (04/1/2017 to 10/31/2020) were used to select adult patients with VTE initiated on DOACs (index date). Patients with only one DOAC claim during the 45-day landmark period (starting on the index date) were classified as one-and-done and the remaining as continuers. Inverse probability of treatment weighting was used to reweight baseline characteristics between cohorts. VTE recurrence based on the first post-index deep vein thrombosis or pulmonary embolism event was compared using weighted Kaplan-Meier and Cox proportional hazard models from landmark period end to clinical activity or data end. RESULTS: 27% of patients initiating DOACs were classified as one-and-done. After weighting, 117,186 and 116,587 patients were included in the one-and-done and continuer cohorts, respectively (mean age 60 years; 53% female; mean follow-up 15 months). After 12 months of follow-up, the probability of VTE recurrence was 3.99% and 3.36% in the one-and-done and continuer cohorts; the risk of recurrence was 19% higher in the one-and-done cohort (hazard ratio [95% confidence interval] = 1.19 [1.13, 1.25]). CONCLUSION: Substantial proportion of patients discontinued DOAC therapy after the first fill, which was associated with significantly higher risk of VTE recurrence. Early access to DOACs should be encouraged to reduce the risk of VTE recurrence.

Attainment of early, deep prostate-specific antigen response in metastatic castration-sensitive prostate cancer: A comparison of patients initiated on apalutamide or enzalutamide.

BACKGROUND: Deep prostate-specific antigen (PSA) response, defined as a ≥90% decline in PSA (PSA90), is an important early response indicator for achieving radiographic progression-free and overall survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with a next-generation androgen signaling inhibitor (ASI), such as apalutamide or enzalutamide. The objective of this study was to compare deep PSA response among patients with mCSPC newly initiated on apalutamide or enzalutamide. METHODS: Clinical data from 69 community urology practices in the United States were evaluated. Patients with mCSPC were classified into cohorts based on their first dispensation (index date) for apalutamide or enzalutamide and were followed until the earliest of treatment discontinuation, initiation of a new next-generation androgen receptor signaling inhibitor, end of clinical activity (including death), or end of data availability (03/05/2021). Inverse probability of treatment weights (IPTW) were used to reduce baseline confounding. PSA90 was defined as the earliest ≥90% PSA decline relative to baseline PSA. The proportion of patients achieving PSA90 and time to PSA90 were reported using weighted Kaplan-Meier analysis and weighted Cox proportional hazards models, respectively. RESULTS: The apalutamide and enzalutamide cohorts comprised 186 and 165 patients, respectively. Patient characteristics were generally well balanced after IPTW. By 6 months, patients initiated on apalutamide had a 56% greater likelihood of attaining PSA90 than those initiated on enzalutamide (P = 0.014). This result remained significant through the end of the observation period. The median time to achieving PSA90 was 3.1 months with apalutamide and 5.2 months with enzalutamide. CONCLUSIONS: This real-world study demonstrated that apalutamide initiation is associated with a significantly higher likelihood of achieving ≥90% reduction in PSA as compared to initiation of enzalutamide. Moreover, this deep PSA response was observed to occur earlier with apalutamide treatment than with enzalutamide.