Evaluation of adverse clinical outcomes in patients with inflammatory bowel disease receiving different sequences of first- and second-line biologic treatments: findings from ROTARY.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at risk of developing dysplasia and, subsequently, colorectal cancer (CRC) owing to chronic inflammation. Patients may also experience other severe disease complications, such as hospitalization and surgery. Several biologics are available for the treatment of patients with IBD and some patients require multiple lines of treatment owing to loss of response or tolerability to their prescribed biologic. Previous studies suggest that the choice of initial biologic treatment may impact the outcomes of later treatment lines. In this study, we assessed adverse clinical outcomes in patients with Crohn's disease (CD) or ulcerative colitis (UC) who received different biologic treatment sequences. METHODS: ROTARY part B was a retrospective cohort study using the Optum® Clinical Database that evaluated the incidences of IBD-related hospitalization, IBD-related surgery, dysplasia, CRC, and infections in patients with CD or UC who received two biologics successively. First-line biologics included adalimumab, infliximab, ustekinumab (CD only), and vedolizumab; second-line biologics included infliximab and adalimumab. RESULTS: In patients with CD, the treatment sequence of ustekinumab to infliximab was associated with the highest overall incidences of hospitalization (51.9%), surgery (40.7%), CRC (3.7%), and infection (37.0%). Vedolizumab followed by an anti-tumor necrosis factor alpha (anti-TNFα) treatment was associated with a significantly lower risk of experiencing an adverse medical event (hospitalization, surgery, or infection) than two successive anti-TNFα treatments (odds ratio, 1.526; 95% confidence interval, 1.004-2.320; P < 0.05). In patients with UC, the treatment sequence of vedolizumab to adalimumab resulted in the lowest overall incidence of adverse outcomes (20.3%, 6.3%, 0.0%, 6.3%, and 4.7% for hospitalization, surgery, CRC, dysplasia, and infection, respectively). CONCLUSIONS: We describe differences in adverse clinical outcomes associated with sequencing of biologics in patients with CD or UC and demonstrate favorable results in patients who received vedolizumab as a first-line biologic. These results provide potential guidance to clinicians choosing sequences of biologic treatments in patients with IBD.

Comparative analysis of real-world adherence and persistence patterns with vibegron, mirabegron, and anticholinergics in patients with overactive bladder: A retrospective claims study.

INTRODUCTION: Vibegron is a selective ß3-adrenergic receptor agonist that was approved by the US Food and Drug Administration in December 2020 for the treatment of overactive bladder in adults. This retrospective study assessed US pharmacy claims data to evaluate the real-world adherence and persistence of vibegron compared with mirabegron and with anticholinergics. MATERIALS AND METHODS: This analysis used the Optum Research Database to identify adults with ≥1 pharmacy claim for vibegron, mirabegron, or an anticholinergic from April 1, 2021, to August 31, 2022. Patients had ≥ 90 days of continuous commercial or Medicare medical and pharmacy coverage preindex and ≥ 60 days of continuous pharmacy coverage postindex. Two independent propensity-score models matched patients treated with (1) vibegron versus mirabegron and (2) vibegron versus anticholinergics on key variables such as demographics and clinical characteristics, index copay, days' supply, and time of entry into analysis (index quarter). Adherence was measured by proportion of days covered (PDC) from index to the end of follow-up and was defined as PDC ≥ 80%. Persistence was defined as days to discontinuation of index medication (first 30-day gap) or end of follow-up. RESULTS: The matched vibegron and mirabegron cohorts included 4921 and 9842 patients, respectively, and the matched vibegron and anticholinergic cohorts included 4676 and 9352 patients, respectively. Patients receiving vibegron had greater mean PDC versus patients receiving mirabegron (0.67 vs. 0.64, respectively; p < 0.001) or anticholinergics (0.67 vs. 0.58; p < 0.001). A greater percentage of patients receiving vibegron were adherent versus those receiving mirabegron (49.0% vs. 45.1%, respectively; p < 0.001) or anticholinergics (49.1% vs. 38.5%; p < 0.001). Persistence was longer with vibegron compared with both mirabegron (median [95% CI], 171 [159-182] vs. 128 [122-137] days, respectively; p < 0.001) and anticholinergics (172 [159-183] vs. 91 [91] days; p < 0.001). CONCLUSION: In this retrospective analysis of pharmacy claims data, patients receiving vibegron exhibited significantly higher adherence and demonstrated longer persistence in comparison to matched patient cohorts receiving either mirabegron or anticholinergics.

Low Meningococcal Vaccination Rates Among Patients With Newly Diagnosed Complement Component Deficiencies in the United States.

Meningococcal vaccination is recommended for patients with complement component deficiencies (CDs) in the United States. In this retrospective database study, only 4.6% and 2.2% of patients received MenACWY and MenB vaccination, respectively, within 3 years of CD diagnosis. Thus, meningococcal vaccination rates among patients with CDs need to be improved.

Impact of mepolizumab on exacerbations in severe asthma: Results from a U.S. insurance claims data base.

Background: In controlled clinical studies, mepolizumab has been shown to reduce exacerbation rates and the use of oral corticosteroids as well as improve asthma control and health-related quality of life compared with placebo in patients with severe eosinophilic asthma. However, real-world data on the impact of mepolizumab on clinical outcomes are limited. Objective: To evaluate the effect of mepolizumab on asthma exacerbations and asthma exacerbation-related costs in patients with severe asthma in U.S. clinical practice. Methods: This retrospective cohort study used U.S. administrative claims data from patients ages ≥12 years and with severe asthma at mepolizumab treatment initiation (index date; identification period, January 2015-June 2017) who had received two or more mepolizumab administrations within 180 days of the index date and had no evidence of treatment with another asthma biologic. The exacerbation rate and exacerbation-related costs were assessed in both the 12 months before mepolizumab initiation (baseline period) and the following 12 months (follow-up period). A clinical trial-like cohort was identified, defined as patients with two or more baseline exacerbations and ≥10 administrations during follow-up. Results: A total of 201 patients were included in the overall population and 74 patients in the clinical trial-like cohort. Mepolizumab significantly reduced the exacerbation rate between the baseline and follow-up periods in both the overall population and the clinical trial-like cohort (p < 0.001), which corresponded to 33.6% and 48.6% reductions, respectively. The rate of exacerbations in patients who required hospitalization between the baseline and follow-up periods was also reduced by 35.3% (p = 0.080) and 68.2% (p = 0.015) in the overall population and in the clinical trial-like cohort, respectively. Cost data were inconclusive. Conclusion: This study, which used real-world data, demonstrated that mepolizumab is associated with reductions in asthma exacerbations, in line with the findings from controlled clinical studies. These results provided further evidence of the effectiveness of mepolizumab in a real-world setting.

Cost of Disease Progression in Patients with Chronic Lymphocytic Leukemia, Acute Myeloid Leukemia, and Non-Hodgkin's Lymphoma.

INTRODUCTION: To reduce health care costs and improve care, payers and physician groups are switching to quality-based and episodic or bundled-care models. Disease progression and associated costs may affect these models, particularly if such programs do not account for differences in disease severity and progression risk within the cohort. This study estimated the incremental cost of disease progression in patients diagnosed with chronic lymphoid leukemia (CLL), acute myeloid leukemia (AML), and non-Hodgkin's lymphoma (NHL) and compared costs among patients with and without progression. METHODS: This was a retrospective study using U.S. administrative claims data from commercial and Medicare Advantage health care enrollees with evidence of CLL, AML, and NHL and systemic antineoplastic agent use from July 1, 2006 to August 31, 2014. Outcome measures included disease progression, 12-month health care costs, and 3-year cumulative predictive health care costs. RESULTS: Of 1,056 patients with CLL, 514 patients with AML, and 7,601 patients with NHL, 31.1% of patients with CLL, 63.8% of those with AML, and 36.9% of those with NHL had evidence of disease progression. Among patients with CLL and NHL, adjusted and unadjusted health care costs were significantly higher among progressors versus nonprogressors. Per-patient-per-month costs, accounting for variable follow-up time, were almost twice as high among progressors versus nonprogressors in patients with CLL, AML, and NHL. In each of the three cancer types, the longer disease progression was delayed, the lower the health care costs. CONCLUSION: Progression of CLL, AML, and NHL was associated with higher health care costs over a 12-month period. Delaying cancer progression resulted in a substantial cost reduction in patients with all three cancer types. IMPLICATIONS FOR PRACTICE: Data on the rates and incremental health care costs of disease progression in patients with hematologic malignancies are lacking. This study estimated the incremental costs of disease progression in patients diagnosed with chronic lymphocytic leukemia, acute myeloid leukemia, and non-Hodgkin's lymphoma and compared health care costs in patients with and without evidence of disease progression in a real-world population. The data obtained in this study will assist future studies in quantifying the cost impact of decreased progression rates and will inform payers and physician groups about setting rates for episode and bundled payment programs.

Cost of Disease Progression in Patients with Metastatic Breast, Lung, and Colorectal Cancer.

INTRODUCTION: To reduce health care costs and improve care, payers and physician groups are piloting value-based and episodic or bundled-care payment models in oncology. Disease progression and associated costs may affect these models, particularly if such programs do not account for disease severity and progression risk across patient populations. This study estimated the incremental cost of disease progression in patients diagnosed with metastatic breast cancer (mBC), colorectal cancer (mCRC) and lung cancer (mLC) and compared costs among patients with and without progression. METHODS: This was a retrospective study using U.S. administrative claims data from commercial and Medicare Advantage health care enrollees with evidence of mBC, mCRC, and mLC and systemic antineoplastic agent use from July 1, 2006, to August 31, 2014. Outcome measures included disease progression, 12-month health care costs, and 3-year cumulative predictive health care costs. RESULTS: Of 5,709 patients with mBC, 3,707 patients with mCRC, and 5,201 patients with mLC, 56.8% of patients with mBC, 58.1% of those with mCRC, and 80.3% of those with mLC patients had evidence of disease progression over 12 months. Among patients with mBC and mCRC, adjusted and unadjusted health care costs were significantly higher among progressors versus nonprogressors. Per-patient-per-month costs, which accounted for variable follow-up time, were almost twice as high among progressors versus nonprogressors in patients with mBC, mCRC, and mLC. In each of the three cancer types, delays in progression were associated with lower health care costs. CONCLUSION: Progression of mLC, mBC, and mCRC was associated with higher health care costs over a 12-month period. Delayed cancer progression was associated with substantial cost reductions in patients with each of the three cancer types. IMPLICATIONS FOR PRACTICE: Data on the rates and incremental health care costs of disease progression in patients with solid tumor cancers are lacking. This study estimated the incremental costs of disease progression in patients diagnosed with lung cancer, breast cancer, and colorectal cancer and compared health care costs in patients with and without evidence of disease progression in a real-world population. The data obtained in our study quantify the economic value of delaying or preventing disease progression and may inform payers and physician groups about value-based payment programs.

Health Care Resource Use and Costs Pre- and Post-Treatment Initiation With Linaclotide: Retrospective Analyses of a U.S. Insured Population.

As expected, pharmacy costs increased with the introduction of this new treatment in a market dominated by over-the-counter and generic treatments. On the other hand, outpatient GI-related and irritable bowel disease health care resource use and costs substantially decreased among commercial and Medicare patients following linaclotide treatment initiation.

Drivers of Healthcare Costs Among the Costliest Patients With Psoriasis Over Three Years in a United States Health Plan.

OBJECTIVE: To compare patients with psoriasis by cost level over 3 years.

METHODS: Psoriasis patients in a large US health plan in 2011-2013 were identified. Four groups were created by healthcare costs excluding biologics: patients having top 10% of costs in all 3 years (Top), top 10% in 2 of 3 years (High), bottom 90% in 2 of 3 years (Medium), and bottom 90% in all 3 years (Bottom). Comorbidities, utilization, and costs between groups were compared.

RESULTS: The study included 18,653 patients: 514 (3%), 805 (4%), 2,443 (13%), and 14,891 (80%) patients in the Top, High, Medium, and Bottom groups, respectively. Significantly more patients in the Top vs Bottom group had diabetes (31.1% vs 9.4%), cardiovascular disease (26.5% vs 4.3%), psoriatic arthritis (25.7% vs 10.7%), depression (27.8% vs 6.9%), and anxiety (22.0% vs 7.9%) in 2011 (all P less than 0.05). Patients in the Top group had more unique 2011 prescriptions (17.7 vs 6.6; P less than 0.001) than the Bottom group, but similar biologic use (22.4% vs 21.6%). Patients in the Top, High, Medium, and Bottom groups had mean 2011 total costs of $68,913, $40,575, $24,292, and $8,815, and contributed to 14%, 13%, 23%, and 51% of the overall costs, respectively. Mean total costs increased 14-18% over time for all groups. Although mean 2011 total costs for patients in the Top group were 7.8 times of those in the Bottom group, psoriasis-related costs were less disparate ($8,716 vs $4,541). Compared with patients in the Bottom group, those in the Top group were more likely to have any 2011 hospitalization (36.8% vs 2.6%; psoriasis-related: 11.1% vs 0.7%) or emergency visit (50.8% vs 20.8%; psoriasis-related: 3.9% vs 1.0%).

CONCLUSION: The costliest patients with psoriasis had significantly higher prevalence of comorbidities, prescription fills, inpatient and emergency utilization, but not biologic medication use or biologic costs.

J Drugs Dermatol. 2017;16(7):651-658.

Autism occurrence by MMR vaccine status among US children with older siblings with and without autism.

IMPORTANCE: Despite research showing no link between the measles-mumps-rubella (MMR) vaccine and autism spectrum disorders (ASD), beliefs that the vaccine causes autism persist, leading to lower vaccination levels. Parents who already have a child with ASD may be especially wary of vaccinations. OBJECTIVE: To report ASD occurrence by MMR vaccine status in a large sample of US children who have older siblings with and without ASD. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study using an administrative claims database associated with a large commercial health plan. Participants included children continuously enrolled in the health plan from birth to at least 5 years of age during 2001-2012 who also had an older sibling continuously enrolled for at least 6 months between 1997 and 2012. EXPOSURES: MMR vaccine receipt (0, 1, 2 doses) between birth and 5 years of age. MAIN OUTCOMES AND MEASURES: ASD status defined as 2 claims with a diagnosis code in any position for autistic disorder or other specified pervasive developmental disorder (PDD) including Asperger syndrome, or unspecified PDD (International Classification of Diseases, Ninth Revision, Clinical Modification 299.0x, 299.8x, 299.9x). RESULTS: Of 95,727 children with older siblings, 994 (1.04%) were diagnosed with ASD and 1929 (2.01%) had an older sibling with ASD. Of those with older siblings with ASD, 134 (6.9%) had ASD, vs 860 (0.9%) children with unaffected siblings (P < .001). MMR vaccination rates (≥1 dose) were 84% (n = 78,564) at age 2 years and 92% (n = 86,063) at age 5 years for children with unaffected older siblings, vs 73% (n = 1409) at age 2 years and 86% (n = 1660) at age 5 years for children with affected siblings. MMR vaccine receipt was not associated with an increased risk of ASD at any age. For children with older siblings with ASD, at age 2, the adjusted relative risk (RR) of ASD for 1 dose of MMR vaccine vs no vaccine was 0.76 (95% CI, 0.49-1.18; P = .22), and at age 5, the RR of ASD for 2 doses compared with no vaccine was 0.56 (95% CI, 0.31-1.01; P = .052). For children whose older siblings did not have ASD, at age 2, the adjusted RR of ASD for 1 dose was 0.91 (95% CI, 0.67-1.20; P = .50) and at age 5, the RR of ASD for 2 doses was 1.12 (95% CI, 0.78-1.59; P = .55). CONCLUSIONS AND RELEVANCE: In this large sample of privately insured children with older siblings, receipt of the MMR vaccine was not associated with increased risk of ASD, regardless of whether older siblings had ASD. These findings indicate no harmful association between MMR vaccine receipt and ASD even among children already at higher risk for ASD.

A Real-World Study of Switching From Allopurinol to Febuxostat in a Health Plan Database.

OBJECTIVE: The objective of this study was to assess the real-world comparative effectiveness of continuing on allopurinol versus switching to febuxostat. METHODS: In a retrospective claims data study of enrollees in health plans affiliated with Optum, we evaluated patients from February 1, 2009, to May 31, 2012, with a gout diagnosis, a pharmacy claim for allopurinol or febuxostat, and at least 1 serum uric acid (SUA) result available during the follow-up period. Univariate and multivariable-adjusted analyses (controlling for patient demographics and clinical factors) assessed the likelihood of SUA lowering and achievement of target SUA of less than 6.0 mg/dL or less than 5.0 mg/dL in allopurinol continuers versus febuxostat switchers. RESULTS: The final study population included 748 subjects who switched to febuxostat from allopurinol and 4795 continuing users of allopurinol. The most common doses of allopurinol were 300 mg/d or less in 95% of allopurinol continuers and 93% of febuxostat switchers (prior to switching); the most common dose of febuxostat was 40 mg/d, in 77% of febuxostat switchers (after switching). Compared with allopurinol continuers, febuxostat switchers had greater (1) mean preindex SUA, 8.0 mg/dL versus 6.6 mg/dL (P < 0.001); (2) likelihood of postindex SUA of less than 6.0 mg/dL, 62.2% versus 58.7% (P = 0.072); (3) likelihood of postindex SUA of less than 5.0 mg/dL, 38.9% versus 29.6% (P < 0.001); and (4) decrease in SUA, 1.8 (SD, 2.2) mg/dL versus 0.4 (SD, 1.7) mg/dL (P < 0.001). In multivariable-adjusted analyses, compared with allopurinol continuers, febuxostat switchers had significantly higher likelihood of achieving SUA of less than 6.0 mg/dL (40% higher) and SUA of less than 5.0 mg/dL (83% higher). CONCLUSIONS: In this "real-world" setting, many patients with gout not surprisingly were not treated with maximum permitted doses of allopurinol. Patients switched to febuxostat were more likely to achieve target SUA levels than those who continued on generally stable doses of allopurinol.

Discrete choice experiment to estimate breast cancer patients' preferences and willingness to pay for prophylactic granulocyte colony-stimulating factors.

OBJECTIVES: Rising out-of-pocket costs for cancer patients have increased shared decision making. Clinical guidelines recommend prophylactic granulocyte colony-stimulating factor (G-CSF) for patients receiving chemotherapy with a 20% or greater risk of febrile neutropenia. A discrete choice experiment was conducted to explore breast cancer patients' preferences and willingness to pay (WTP) for prophylactic G-CSF to decrease the risk of chemotherapy-induced febrile neutropenia. METHODS: An online discrete choice experiment questionnaire survey of a national US convenience sample of self-reported breast cancer patients with prior chemotherapy treatment was conducted. Sixteen paired G-CSF treatment scenarios, each with four attributes (risk of disruption to chemotherapy schedule due to low white blood cell counts, risk of developing an infection requiring hospitalization, frequency of administration, and total out-of-pocket cost) were presented with a follow-up "no treatment" option. Participant preferences and WTP out of pocket were estimated by logistic regression. RESULTS: Participants (n = 296) preferred G-CSF regimens with lower out-of-pocket costs, lower risk of chemotherapy disruption, lower risk of infection, and greater convenience (one G-CSF injection per chemotherapy cycle). Participants' WTP was $1076 out of pocket per cycle to reduce the risk (high to low) of disrupting their chemotherapy schedule, $884 per cycle to reduce the risk (24% [high] to 7% [low]) of infection, and $851 per cycle to decrease the number of G-CSF injections (11 to 1) per cycle. CONCLUSIONS: Participants highly valued specific features of prophylactic G-CSF treatment including maintaining their chemotherapy schedule, lowering their risk of infection, and reducing the number of injections. Physicians should consider patient preferences to inform the best treatment choices for individual patients.

The relationship of depression to antiepileptic drug adherence and quality of life in epilepsy.

We sought to examine the impact of depression upon antiepileptic drug (AED) adherence in patients with epilepsy. We administered the Center for Epidemiologic Studies Depression Scale (CES-D), Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Seizure Severity Questionnaire (SSQ), and Quality of Life in Epilepsy-10 (QOLIE-10) and measured AED adherence by utilizing the medication possession ratio (MPR) in adult patients with epilepsy identified through a pharmacy claims database. From a sampling frame of over 10,000 patients identified in claims, 2750 were randomly selected and contacted directly by mail to participate in the cross-sectional survey. A total of 465 eligible patients completed a survey. Survey data were combined with administrative claims data for analysis. We conducted a path analysis to assess the relationships between depression, adherence, seizure severity, and quality of life (QOL). Patients with depression scored significantly worse on measures of seizure severity (p=.003), QOL (p<.001), and adherence (p=.001). On path analysis, depression and QOL and seizure severity and QOL were related, but only the NDDI-E scores had a significant relationship with medication adherence (p=.001). Depression as measured by the NDDI-E was correlated with an increased risk of AED nonadherence. Depression or seizure severity adversely impacted QOL. These results demonstrate yet another important reason to screen for depression in epilepsy.

The economic burden of pulmonary arterial hypertension (PAH) in the US on payers and patients.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare condition that can ultimately lead to right heart failure and death. In this study we estimated the health care costs and resource utilization associated with PAH in a large US managed care health plan. METHODS: Subjects with claims-based evidence of PAH from 1/1/2004 to 6/30/2010 (identification period) were selected. To be included in the final PAH study sample, subjects were required to have ≥2 claims with a primary PH diagnosis; ≥2 claims with a PAH related-diagnosis (connective tissue diseases, congenital heart diseases, portal hypertension); and ≥1 claim with evidence of a PAH-indicated medication. The earliest date of a claim with evidence of PAH-indicated medication during the identification period was set as the index date. Health care costs and resource utilization were compared between an annualized baseline period and a 12 month follow-up period. RESULTS: 504 PAH subjects were selected for the final study cohort. Estimated average total health care costs were approximately 16% lower in the follow-up period compared to the baseline period (follow-up costs = $98,243 [SD = 110,615] vs. baseline costs = $116,681 [SD = 368,094], p < 0.001), but substantively high in each period relative to costs reported for other chronic diseases. Pharmacy costs were significantly higher in the follow-up period vs. the baseline period, ($38,514 [SD = 34,817] vs. $6,440 [SD = 12,186], p < 0.001) but medical costs were significantly lower in the follow-up vs. baseline ($59,729 [SD = 106,683] vs. $110,241 [SD = 368,725], p < 0.001). These costs were mirrored in health-care resource utilization estimates. The average counts of ambulatory visits and inpatient stays were lower in the follow-up vs. the baseline (both p < 0.001). Results varied in exploratory analyses when less restrictive subject identification algorithms were used. CONCLUSIONS: Subjects with evidence of PAH had substantively high health care costs. Medical costs appeared to decrease following PAH medication use, but with a concomitant increase in pharmacy costs.

Relative vaccine effectiveness of MF59-adjuvanted vs high-dose trivalent inactivated influenza vaccines for prevention of test-confirmed influenza hospitalizations during the 2017-2020 influenza seasons.

OBJECTIVES: This study evaluated relative vaccine effectiveness (rVE) of MF59-adjuvanted trivalent inactivated influenza vaccine (aTIV) vs high-dose trivalent inactivated influenza vaccine (HD-TIV) for prevention of test-confirmed influenza emergency department visits and/or inpatient admissions ("ED/IP") and for IP admissions alone pooled across the 2017-2020 influenza seasons. Exploratory individual season analyses were also performed. METHODS: This retrospective test-negative design study included United States (US) adults age ≥65 years vaccinated with aTIV or HD-TIV who presented to an ED or IP setting with acute respiratory or febrile illness during the 2017-2020 influenza seasons. Test-positive cases and test-negative controls were grouped by vaccine received. The rVE of aTIV vs HD-TIV was evaluated using a combination of inverse probability of treatment weighting and logistic regression to adjust for potential confounders. RESULTS: Pooled analyses over the three seasons found no significant differences in the rVE of aTIV vs HD-TIV for prevention of test-confirmed influenza ED/IP (-2.5% [-19.6, 12.2]) visits and admissions or IP admissions alone (-1.6% [-22.5, 15.7]). The exploratory individual season analyses also showed no significant differences. CONCLUSIONS: Evidence from the 2017-2020 influenza seasons indicates aTIV and HD-TIV are comparable for prevention of test-confirmed influenza ED/IP visits in US adults age ≥65 years.

Real-world use of inotuzumab ozogamicin is associated with lower health care costs than blinatumomab in patients with acute lymphoblastic leukemia in the first relapsed/refractory setting.

Aim: To compare all-cause and acute lymphoblastic leukemia (ALL)-related healthcare resource utilization (HCRU) and costs among patients receiving inotuzumab ozogamicin (InO) and blinatumomab (Blina) for ALL in the first relapsed/refractory (R/R) setting. Patients & methods: We studied retrospective claims for adult commercial and Medicare Advantage enrollees with ALL receiving InO (n = 29) or Blina (n = 23) from 1 January 2015 to 16 February 2021. Mean per-patient-per-month (PPPM) HCRU and total costs were described and multivariable-adjusted PPPM total all-cause and ALL-related predicted costs were calculated. Results: Mean monthly ALL-related hospitalizations were the same for patients receiving InO and Blina (PPPM = 0.8 stays); however, the length of ALL-related hospital stay was almost twice as long among patients receiving Blina versus InO (ALL-related: InO = 7.6 days; Blina = 14.1 days; p = 0.346). In multivariable models, total ALL-related costs were 43% lower for InO compared with Blina (PPPM costs: InO = $93,767; Blina = $163,470; p = 0.021). Conclusion: In the first R/R setting, patients who used InO had significantly lower all-cause and ALL-related costs compared with patients who used Blina, in part driven by hospitalization patterns.

Real-World Adherence to and Persistence with Vibegron in Patients with Overactive Bladder: A Retrospective Claims Analysis.

INTRODUCTION: Vibegron is a ß3-adrenergic receptor agonist approved for overactive bladder (OAB). This analysis assessed real-world adherence and persistence with vibegron in patients with OAB, along with demographics and clinical characteristics associated with adherence and persistence. METHODS: This retrospective study used the Optum Research Database to identify patients treated with vibegron from April 2021 to August 2022 (identification period). Patients had ≥ 60 days of continuous pharmacy coverage in a commercial or Medicare Advantage plan following the index fill (follow-up). Adherence was assessed as proportion of days covered (PDC) from index to end of follow-up and was defined as PDC ≥ 80%. Persistence was measured as days to discontinuation of therapy (30-day gap) or end of follow-up. Data for adherence and persistence are presented descriptively. Characteristics associated with adherence and persistence were analyzed using multivariable models among patients with medical and pharmacy benefits during the 90 days before index (baseline). RESULTS: Overall, 9992 patients had a vibegron claim during the identification period; 9712 had ≥ 2 months of follow-up. Mean (SD) age was 74.2 (10.7) years; 68.2% were female. Mean (SD) PDC was 0.64 (0.34). Median (95% confidence interval) persistence was 142 (132-153) days. Of the 5073 patients who were ≥ 18 years old with continuous baseline pharmacy and medical benefits ≥ 90 days before index, 2497 (49.2%) were adherent. Patients were more likely to be adherent and persistent if they received a greater days' supply for the index fill and had baseline medication count ≥ 6. Patients were more likely to discontinue if their index copay was > $45. CONCLUSION: Nearly half of the patients initiating vibegron were adherent. Factors associated with adherence and persistence were more likely to be related to prescribing practices than patient characteristics. These results suggest it may be best to follow up with patients approximately 4 to 5 months after initiating treatment with vibegron.

Vibegron is a newer drug for treating overactive bladder. Vibegron was safe and worked well in clinical trials. However, there is no information on use of vibegron in a real-world population that is not a clinical trial. This study looked at how consistently and how long patients took vibegron after starting it. It also looked at what was common in patients who took vibegron consistently. To do this, the study used pharmacy prescription data from April 2021 to August 2022. It examined adherence to the study medication for each patient. Adherence is how many days patients had medication on hand compared to how long they were followed. The study also looked at persistence to the study medication. Persistence is how long a patient takes a medication before they stop taking it. Researchers then examined if there were reasons a patient may or may not take vibegron as prescribed. The study included prescription data for 9712 patients. The average age was 74 years and 68% of patients were female. Patients had their medication 64% of the time (adherence). On average, patients took their medication for 142 days before stopping (persistence). Patients had better adherence and persistence if they received a larger supply of medication at the pharmacy when first prescribed the medication and if they had more medications overall. Patients' age and gender did not affect adherence and persistence. Vibegron may be a good option for patients with overactive bladder. Follow-up with a provider may be considered 4 to 5 months after starting vibegron.

Estimation of false discovery rate using sequential permutation p-values.

We consider the problem of testing each of m null hypotheses with a sequential permutation procedure in which the number of draws from the permutation distribution of each test statistic is a random variable. Each sequential permutation p-value has a null distribution that is nonuniform on a discrete support. We show how to use a collection of such p-values to estimate the number of true null hypotheses m0 among the m null hypotheses tested and how to estimate the false discovery rate (FDR) associated with p-value significance thresholds. We use real data analyses and simulation studies to evaluate and illustrate the performance of our proposed approach relative to standard, more computationally intensive strategies. We find that our sequential approach produces similar results with far less computational expense in a variety of scenarios.

Real-world comorbidities and treatment patterns of patients with acromegaly in two large US health plan databases.

Acromegaly is a rare, chronic, and debilitating disease that results from excessive growth hormone production. Clinically, this disease is associated with enlargement of soft tissue, excessive skeletal growth, and increased risk of cardiovascular disease. Acromegaly is often diagnosed late, when a wide range of comorbidities may already be present. First-line therapy for acromegaly is typically surgery; but a number of highly-specific pharmacological agents have recently enabled a more aggressive medical management of acromegaly. Since surgical cure of acromegaly is low for macroadenomas, medical control of active acromegaly is an important component of treatment. There are no published US data currently available regarding real-world rates of comorbidities and treatment patterns among patients with acromegaly. This retrospective study examined the comorbidities and treatment patterns of 949 health plan enrollees, who had acromegaly diagnosis and/or procedure codes in an administrative claims database from July 1, 2002 through June 30, 2010. Acromegaly was associated with high rates of hypertension and diabetes along with a number of other comorbidities. The incidence of comorbidities was highest among patients with acromegaly-related treatment, which may have resulted, in part, from inadequate disease management and/or poor disease control. Unexpectedly, 55% of patients identified with acromegaly received no treatment for acromegaly (i.e., surgery, radiotherapy, and medication) and only 28% received a medication treatment during the observation period. However, some patients may have received a curative surgery prior to the observation period, which may have reduced the use of other acromegaly-related treatments during the study period. Of those treated with medications, the most common first medications were octreotide, cabergoline, and bromocriptine. Given the high incidence of serious comorbidities associated with active acromegaly, earlier diagnosis and treatment, along with appropriate follow-up care, may potentially avoid the life-long consequences of uncontrolled disease.

Real-World Persistence of Successive Biologics in Patients With Inflammatory Bowel Disease: Findings From ROTARY.

BACKGROUND: Patients with inflammatory bowel disease (IBD) may receive multiple successive biologic treatments in clinical practice; however, data are limited on the comparative effectiveness of biologics and the impact of treatment sequence on outcomes. METHODS: The ROTARY (Real wOrld ouTcomes Across tReatment sequences in inflammatorY bowel disease patients) study was a retrospective, observational cohort study conducted using data from the Optum Clinical Database between January 1, 2012, and February 29, 2020. Adult patients with Crohn's disease (CD) or ulcerative colitis (UC) who received 2 biologics successively were included. Biologic treatment sequences were analyzed descriptively. Cox proportional hazards models, adjusted for baseline demographics and clinical characteristics, were used to estimate the hazard ratio of switching or discontinuation for each first- and second-line biologic compared with first- and second-line adalimumab, respectively. RESULTS: In total, 4648 patients with IBD (CD, n = 3008; UC, n = 1640) were identified. Most patients received tumor necrosis factor α antagonist (anti-TNFα) treatment followed by another anti-TNFα treatment or vedolizumab. Vedolizumab and infliximab had 39.4% and 34.6% lower rates of switching or discontinuation than adalimumab, respectively, as first-line biologics in patients with CD and 30.8% and 34.3% lower rates as first-line biologics in patients with UC, respectively. Vedolizumab, infliximab, and ustekinumab had 47.2%, 40.0%, and 43.5% lower rates of switching or discontinuation than adalimumab, respectively, as second-line biologics in CD and 56.5%, 43.0%, and 45.6% lower rates as second-line biologics in patients with UC, respectively. CONCLUSIONS: Although anti-TNFα treatments were most commonly prescribed, the adjusted rates of discontinuation for adalimumab as both a first- and second-line biologic were higher than for vedolizumab, infliximab, or ustekinumab.

Patients with inflammatory bowel disease are commonly treated with different sequences of biologics. This study shows that patients who receive adalimumab as their first or second biologic treatment either stop or switch to another biologic at a greater rate than those who are treated with vedolizumab, infliximab, and ustekinumab.

Medical costs and health-care resource use in patients with inflammatory myopathies in an insured population.

INTRODUCTION: In this study we determined the health-care costs and resource utilization associated with idiopathic inflammatory myopathies (IIMs) in a large managed care plan in the USA. METHODS: Myositis subjects ≥18 years of age with claims-based evidence of IIMs were identified from a health plan database. Subjects were matched with unaffected controls, and costs and resource use were determined during a 12-month period. RESULTS: A total of 1781 newly diagnosed IIM subjects were matched to 5343 controls, and 2697 subjects with existing disease were matched to 8091 controls. Mean overall annual medical costs were higher among newly diagnosed subjects ($16,319 vs. $4926, P < 0.001) and subjects with an existing IIM ($15,539 vs. $5210, P < 0.001) in comparison to controls. IIM subjects had significantly higher mean counts of ambulatory visits, specialist visits, and inpatient hospital stays compared with controls (all P < 0.001). CONCLUSION: Our analysis suggests that IIMs have increased medical costs and resource use.