Michael Lee Ganz

In the United States, while meningococcal vaccines are available and recommended for adolescents and young adults, coverage remains low and disparities persist. We evaluated meningococcal serogroups A, C, W, Y (MenACWY) and B (MenB) vaccine uptake, completion, and compliance using a cross-sectional analysis of National Immunization Survey-Teen (NIS-Teen) data (2015-2021) and a cohort analysis of commercial claims data (2010-2021). Regression models were used to identify factors associated with vaccine uptake. Included in the NIS-Teen MenACWY and MenB analyses were 138,952 and 177,077 patients, respectively. Included in the claims MenACWY and MenB analyses were 953,905 and 818,424 patients, respectively. In 2021, MenACWY uptake was 86.4% (95% confidence interval [CI]: 83.6-88.8%) among ≤13-year-olds (NIS-Teen) and 63.2% (62.8-63.5%) among 11-12-year-olds (claims). MenB was 33.7% (30.5-37.1%) among ≤17-year-olds (NIS-Teen), 41.6% (41.2-42.0%) among 16-18-year-olds (claims), and 15.0% (14.7-15.4%) among 19-23-year-olds (claims). The states with the lowest and highest MenB uptake by ≤17-year-olds in 2021 (NIS-Teen) were Minnesota (10.1% [3.9-23.6%]) and North Dakota (69.9% [52.1-83.2%]). Factors associated with MenACWY uptake included living in a state with a vaccine mandate, Black or Hispanic race (versus White), and well-child visit attendance. Factors associated with MenB uptake included having Medicaid (versus private insurance) and Hispanic race (versus White). The findings suggest that meningococcal vaccination coverage disparities persist across vaccines, age, geography, and race and ethnicity. Higher MenACWY (versus MenB) coverage suggests the benefit of routine recommendations. Annual well-child visits and simplified vaccination schedules could reduce vaccination access barriers.

Invasive meningococcal disease (IMD) is a life-threatening yet vaccine-preventable disease, with vaccines approved and recommended in the United States by the Centers for Disease Control and Prevention. This study assessed complications, mortality, healthcare resource utilization (HCRU), and healthcare costs among a sample of commercially-insured individuals living in the United States who experienced IMD. We used retrospective data from large claims databases limited to individuals with IMD covered by commercial health plans between January 2010–March 2022. Health outcomes, HCRU, and healthcare costs were analyzed during the acute (index date to 30 days post-hospital discharge) and post-acute (end of acute phase to end of follow-up period) phases. Among 618 IMD cases identified, the most common acute phase complications were severe brain damage, renal failure, and autoimmune disease. The most common post-acute phase complications were autoimmune disease, arthralgia, and renal failure. Acute phase HCRU ranged from 72.7 (95% confidence interval [CI] 19.81–186.12) intensive care unit (ICU) stays to 12,102.9 (95% CI 11,201.07–13,058.00) surgeries per 1,000 patient-years. Post-acute phase HCRU ranged from 3.6 (95% CI 1.18–8.50) ICU stays to 7,808.3 (95% CI 7,661.22–7,957.54) specialty physician visits per 1,000 patient-years. Patients with IMD incurred average healthcare costs of $60,866.23 and $145,883.65 during the acute and post-acute phases, respectively. Negative health outcomes and high HCRU and costs were observed among commercially-insured patients with IMD. Our findings suggest that IMD immunization efforts and healthcare interventions targeting education on vaccine recommendations to healthcare providers and patients could help prevent IMD and reduce disease burden.

Background: Spinal muscular atrophy (SMA) is a rare, progressive, neuromuscular disorder. Recent advances in treatment require an updated assessment of burden to inform reimbursement decisions. Objectives: To quantify healthcare resource utilisation (HCRU) and cost of care for patients with SMA. Methods: Cohort study of patients with SMA identified in the Swedish National Patient Registry (2007–2018), matched to a reference cohort grouped into four SMA types (1, 2, 3, unspecified adult onset [UAO]). HCRU included inpatient admissions, outpatient visits, procedures, and dispensed medications. Direct medical costs were estimated by multiplying HCRU by respective unit costs. Average annual HCRU and medical costs were modelled for SMA versus reference cohorts to estimate differences attributable to the disease (i.e., average treatment effect estimand). The trajectory of direct costs over time were assessed using synthetic cohorts. Results: We identified 290 SMA patients. Annualised HCRU was higher in SMA patients compared with reference cohorts. Highest risk ratios were observed for inpatient overnight stays for type 1 (risk ratio [RR]: 29.2; 95% confidence interval [CI]: 16.0, 53.5) and type 2 (RR: 23.3; 95% CI: 16.4,33.1). Mean annual direct medical costs per patient for each year since first diagnosis were greatest for type 1 (€114,185 and SMA-attributable: €113,380), type 2 (€61,876 and SMA-attributable: €61,237), type 3 (€45,518 and SMA-attributable: €44,556), and UAO (€4046 and SMA-attributable: €2098). Costs were greatest in the 2–3 years after the first diagnosis for all types. Discussion and conclusion: The economic burden attributable to SMA is significant. Further research is needed to understand the burden in other European countries and the impact of new treatments.

Corrigendum: Real-World Treatment Patterns of Antiviral Prophylaxis for Cytomegalovirus Among Adult Kidney Transplant Recipients: A Linked USRDS-Medicare Database Study

Background: Electronic health records (EHRs) offer the possibility of using data entry templates to simultaneously document routine clinical care and capture disease-specific measures as discrete data elements that can be used for health services research (HSR). The objective of this study was to determine factors associated with meaningful treatment escalation (MTE) of psoriasis as a pilot study for future real-world HSR studies. Methods: We conducted a retrospective, observational cohort study of psoriasis patients by using data collected during routine clinical care from an EHR using EpiCare® SmartForms. The psoriasis SmartForm records psoriasis disease severity measures and descriptive findings to generate visit notes. These data were extracted and analyzed to identify factors associated with MTE, defined as changing or adding, phototherapy, systemic, or biologic therapy. Results: 473 psoriasis patients met study criteria; 239 underwent MTE between their first and third observed visits. Patients who experienced MTE had more severe disease at Visit 1—assessed by BSA, pPGA, oPGA, and a patient-reported disease severity measure--than patients who did not experience MTE. Other factors associated with MTE included use of topicals only or no active treatment at Visit 1, palmoplantar disease, and involvement of other difficult-to-treat body areas. Patients who underwent MTE experienced larger improvements in disease severity than those who did not. Conclusions: This study highlights how data collected during routine clinical practice can be readily used for real-world retrospective HSR when disease measures are captured as discrete elements. This approach could provide a cost-effective platform to conduct real-world HSR.

Limited data exist on cytomegalovirus (CMV) antiviral treatment patterns among kidney transplant recipients (KTRs). Using United States Renal Database System registry data and Medicare claims (1 January 2011–31 December 2017), we examined CMV antiviral use in 20,601 KTRs who received their first KT from 2011 to 2016. Three-quarters of KTRs started CMV prophylaxis (86.9% of high-, 83.6% of intermediate-, and 31.7% of low-risk KTRs). Median time to prophylaxis discontinuation was 121, 90, and 90 days for high-, intermediate-, and low-risk KTRs, respectively. Factors associated with receiving CMV prophylaxis were high-risk status, diabetes, receipt of a well-functioning kidney graft, greater time on dialysis before KT, panel reactive antibodies ≥80%, and use of antithymocyte globulin, alemtuzumab, and tacrolimus. KTRs were more likely to discontinue CMV prophylaxis if they developed leukopenia/neutropenia, had liver disease, or had a deceased donor. These findings suggest that adherence to the recommended duration of CMV-prophylaxis for high and intermediate-risk patients is suboptimal, and CMV prophylaxis is overused in low-risk patients.

Background Electronic health records (EHRs) offer the possibility of using data entry templates to simultaneously perform routine documentation during clinical care and to capture disease-specific measures as discrete data elements that can be used for health services research (HSR). The objective of this study was to determine factors associated with meaningful treatment escalation of psoriasis as a pilot study for future real-world retrospective and prospective comparative effectiveness studies, including pragmatic clinical trials. Methods We conducted a retrospective, observational cohort study of patients with psoriasis by using data collected in the course of routine clinical care from an EHR using EpiCare® SmartForms customized for psoriasis. The Psoriasis SmartForm records body surface area (BSA) affected, plaque and overall Physician Global Assessments (pPGA and oPGA), and a patient-reported severity rating scale as well as descriptive findings (e.g., lesion locations, symptoms such as itch or pain) to generate visit notes. These clinical data were extracted and analyzed to identify factors associated with meaningful treatment escalation (MTE), defined as changing or adding phototherapy or systemic oral or biologic therapy. Results We identified 473 patients with psoriasis who had at least three consecutive visits between October 2015 and October 2018; 239 patients underwent MTE between their first (Visit 1) and third (Visit 3) observed visits, while 234 patients did not. Patients who experienced MTE had more severe disease at Visit 1 as assessed by BSA, pPGA, oPGA, and the patient-reported measure than patients who did not experience MTE. Other factors associated with MTE included use of topical medications only or no active treatment at Visit 1, palmoplantar disease phenotype and involvement of other difficult-to-treat body areas. After adjusting for potential confounding factors, we found that patients who underwent MTE experienced larger improvements in disease severity than those who did not. Conclusions This study highlights how data collected during routine clinical practice can be readily used for real-world retrospective HSR studies when disease measures are captured discretely. This approach could provide a cost-effective platform to conduct retrospective and prospective real-world studies, pragmatic trials, and comparative effectiveness research.

Guidelines recommends cytomegalovirus (CMV) prophylaxis by CMV serostatus/risk status, as the currently available antiviral agents may lead to myelosuppressive events in kidney transplant recipients (KTRs). Limited data exist for the United States (US) on the such clinical outcomes with CMV prophylaxis KTRs especially stratified by CMV risk strata. We examined the associations between clinical outcomes and CMV prophylaxis among adult KTRs stratified by CMV risk strata. We employed a retrospective cohort design using the US Renal Data System registry-linked Medicare data (2011-2017). The cohort included 22,918 adult KTRs with continuous Medicare Part A & B coverage for ≥ 6-month pre and ≥ 12-month post KT and Part D coverage for ≥ 12-month post- KT. CMV prophylaxis was defined as ≥ 1 prescription fill or medical claim for valacyclovir or valganciclovir at prophylaxis doses within 28 days post-KT. CMV prophylaxis was utilized by 75% of the cohort. In no CMV prophylaxis group, 52.2% and 34.2% of high and intermediate risk KTRs received valganciclovir (as either pre-emptive or deferred therapy), respectively. Among high risk KTRs, CMV prophylaxis group had significantly lower proportions of KTRs with CMV infection, opportunistic infections (OIs) including bacterial, and fungal infections, and new onset of diabetes mellitus (NODAT) compared to no prophylaxis group. There were no differences in the rates of acute rejection or death; however, a trend towards lower rate of graft-failure at 12-month post-KT. Nearly 40% of high-risk KTRs had myelosuppressive events (leukopenia: 18%; neutropenia:15% thrombocytopenia :19%); however, their differences were non-significant except for thrombocytopenia by CMV prophylaxis status (Table 1). CMV infection and myelosuppressive event rates were higher in high-risk than intermediate/low risk KTRs irrespective of CMV prophylaxis status. CMV prophylaxis was associated with lower rates of CMV infection, OIs, NODAT and graft failure compared to no prophylaxis, however, the burden of CMV infection, OIs and myelosuppression was greater in high-risk KTRs indicating further research is needed on factors associated with greater disease burden in high-risk KTRs. Table 1 Amit D. Raval, PhD, Merck and Co., Inc. (Employee) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder)

Cytomegalovirus (CMV) management requires a balance between reducing the risk of CMV infection and avoiding anti-viral toxicities. Limited information is available on the impact of CMV prophylaxis on the healthcare resource use (HCRU) and costs among adult kidney transplant recipients (KTRs) in the United States. Therefore, we examined HCRU and cost associated with CMV prophylaxis stratified by the CMV risk categories among KTRs at 1-year post-KT. We identified a cohort of 22,918 adults first-time KTRs during 2011–2017 using the US Renal Data System registry-linked Medicare data. Additional inclusion criteria were to have continuous coverage in Medicare Part A & B for ≥ 6-month pre- and ≥ 12-month post KT and Medicare Part D for ≥12-month post-KT. CMV prophylaxis was confirmed as ≥ 1 prescription fill for valacyclovir/(val)ganciclovir prophylaxis doses within 28 days post-KT. CMV prophylaxis was utilized in 86%, 82%, and 32% of high, intermediate, and low-risk KTRs with an average cost of prophylaxis per KTRs of &16,241, &9481, and &8,648, respectively. In no prophylaxis groups, valganciclovir was utilized in 52%, 34%, and 36% of KTRs (as either pre-emptive or deferred therapy) with an average cost of &6,719, &2,722, and &431 among high, intermediate, and low-risk KTRs, respectively. Among high-risk KTRs, CMV prophylaxis group had a significantly higher prescription drug cost (&26,060 vs. &13,433) but a lower average direct healthcare medical cost (&84,914 vs. &101,268), mainly due to lower all-cause hospitalization cost (&56,758 vs. &69,852) (Table 1). CMV prophylaxis group had lower rates of all-cause rehospitalization, and CMV-and opportunistic infection (OIs)-related hospitalization compared to no prophylaxis (Table 2). In high-risk KTRs, nearly 32% had myelosuppressive events-related hospitalization, and 15% filled granulocyte colony-stimulating factors with an average cost of &4,695 per treated KTR. CMV prophylaxis had a higher cost of medications but had a lower medical cost with including all-cause and CMV-related hospitalizations. Myelosuppressive events were frequent and resource-intensive especially in high and intermediate-risk KTRs. Amit D. Raval, PhD, Merck and Co., Inc. (Employee) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder)

Dear Editor,We appreciate the interest from Xue et al. in our cost-effectiveness analysis of valbenazine versus deutetrabenazine for the treatment of tardive dyskinesia (TD) [1], and are gratified ...