Acthar Gel in African Americans versus Non-African Americans with Symptomatic Sarcoidosis: Physician Assessment of Patient Medical Records.

Introduction: Sarcoidosis is common among African Americans in the United States. Acthar® Gel is a viable option for the treatment of advanced symptomatic sarcoidosis. This study examined patient characteristics, Acthar Gel utilization, co-medication use, and treatment response based on physicians' assessments among African Americans versus non-African Americans with advanced symptomatic sarcoidosis. Methods: Data from the medical charts of patients were used. During data collection, patients had either completed ≥1 course or received treatment with Acthar Gel for ≥6 months. Results: This study comprised 168 African Americans and 104 non-African Americans. On average, the time since the first diagnosis of sarcoidosis was slightly longer among African Americans than non-African Americans (5.2 versus 4.3 years). Skin, heart, eyes, and joints were the most common extrapulmonary sites involved among both race groups. Shortness of breath, fatigue, bone and joint pain, and wheezing/coughing were the most frequent symptoms among both race groups. A higher proportion of African Americans versus non-African Americans were first-time Acthar Gel users and had not completed treatment during data collection. Patients in both race groups with higher starting doses of Acthar Gel therapy had a shorter treatment duration and vice-versa. A significantly lower proportion of patients among both race groups were on any co-medication after Acthar Gel initiation (p<0.0001). Further, a higher proportion of African Americans versus non-African Americans had a reduction in any co-medication use after Acthar Gel initiation. The mean daily dose of prednisone decreased among African Americans (18.5 to 10.1 mg) and non-African Americans (17.6 to 10.0 mg) after Acthar Gel initiation. Improvement in patient health status and overall symptoms was similar for both race groups. Conclusion: Findings suggest that Acthar Gel improves health outcomes for patients with sarcoidosis, which could help to alleviate health disparities among African Americans, who are disproportionately affected by this disease.

Cost-Effectiveness of Acthar Gel versus Standard of Care for the Treatment of Advanced Symptomatic Sarcoidosis.

Introduction: Sarcoidosis is a multisystem, inflammatory, systemic granulomatous disease with unknown etiology. Despite the current standard of care (SoC), there is an unmet need for the treatment of advanced symptomatic sarcoidosis. This study assessed the cost-effectiveness of Acthar® Gel (repository corticotropin injection) versus SoC in patients with advanced symptomatic sarcoidosis from the United States (US) payer and societal perspectives over 2 and 3 years. Methods: A probabilistic cohort-level state-transition approach was used for this cost-effectiveness analysis. Patients were monitored at the end of a 3-month cycle for the attainment of partial or complete response. Patients in the partial, complete, or no-response state were allowed to transition in each of these states at each 3-month cycle. Following the attainment of response, patients could have a durable response or relapse to a no-response state. Patients in a no-response state received treatment and could transition into a response or no-response state based on the probability of treatment success with the respective treatment. Clinical parameters and health utility data were sourced from the Acthar Gel in Participants with Pulmonary Sarcoidosis (PULSAR) trial (NCT03320070) and healthcare utilization, costs, and disutilities were sourced from the published literature. Base case analysis considered a payer perspective over 2 years. Results: From a payer perspective, Acthar Gel versus SoC results in an incremental cost-effectiveness ratio (ICER) of $134,796 per quality-adjusted life-year (QALY) and $39,179 per QALY over 2 and 3 years, respectively. From a societal perspective, Acthar Gel versus SoC results in an ICER of $117,622 per QALY and $21,967 per QALY over 2 and 3 years, respectively. Sensitivity analysis findings were consistent with the base case. Conclusion: The results from this cost-effectiveness analysis indicate that Acthar Gel is a cost-effective, value-based treatment option for advanced symptomatic sarcoidosis compared to the SoC from the US payer and societal perspectives.

Treatment-Related Cost Analysis of Terlipressin for Adults with Hepatorenal Syndrome with Rapid Reduction in Kidney Function.

INTRODUCTION: Hepatorenal syndrome (HRS), a special form of acute kidney failure, is a rare, acute, life-threatening complication of cirrhosis and has a very poor prognosis. Terlipressin (TERLIVAZ®) is the first and only pharmacological treatment approved by Food and Drug Administration (September 2022) to improve kidney function for adults with HRS with rapid reduction in kidney function. We constructed a decision analytic economic model to estimate the cost per complete response/HRS reversal of terlipressin + albumin from a United States hospital perspective. METHODS: A decision analytic model was developed to estimate the HRS treatment-related cost per response over an HRS hospitalization (assuming 14 days). Patients can experience either HRS reversal (complete response) or no HRS reversal (partial/no response) upon receipt of treatment. The efficacy, safety, and treatment duration data were from published head-to-head randomized international trials. Total treatment cost comprised drug acquisition and treatment-related costs (intensive care unit [ICU], dialysis [intermittent or continuous], pulse oximetry monitoring for terlipressin, and adverse events) sourced from the published literature. Cost per response, defined as the total treatment cost per HRS reversal was estimated for each treatment. The number needed to treat (NNT), defined as the number of patients treated to achieve HRS reversal in 1 additional patient, was estimated. RESULTS: Cost per response of terlipressin + albumin was lower than midodrine and octreotide + albumin (M&O) (US$85,315 vs. $467,794) and norepinephrine + albumin ($81,614 vs. $139,324). NNT for HRS reversal was 2 patients with terlipressin + albumin vs. M&O + albumin and 4 patients with terlipressin + albumin vs. norepinephrine + albumin, respectively. CONCLUSIONS: The analysis shows that terlipressin is a cost-effective treatment due to its higher efficacy and administration in the non-ICU setting. Terlipressin is a value-based treatment option for appropriate adults with HRS with rapid reduction in kidney function.

Hepatorenal syndrome, a functional, progressive kidney failure, is a life-threatening complication of cirrhosis. It is important to improve kidney function in patients who are hospitalized with hepatorenal syndrome considering the cost of treatment. This study assessed the cost per complete response/ hepatorenal syndrome reversal of terlipressin + albumin from a United States hospital perspective. This study shows that terlipressin improves kidney function with lower intensive care unit and dialysis costs compared with unapproved treatments. Terlipressin is a cost-effective, value-based treatment option for appropriate adults with hepatorenal syndrome with rapid reduction in kidney function.

Cost-Effectiveness of Acthar Gel Versus Standard of Care for the Treatment of Exacerbations in Moderate-to-Severe Systemic Lupus Erythematosus.

INTRODUCTION: Despite current standard of care (SoC), there is an unmet need for the treatment of active systemic lupus erythematosus (SLE). The study assessed the cost-effectiveness of Acthar® Gel (repository corticotropin injection) versus SoC treatment in patients with active, moderate-to-severe SLE from the US payer and societal perspectives over 2 and 3 years. METHODS: Cost-effectiveness model was developed using a probabilistic cohort-level state-transition approach. Patients received Acthar Gel in an exacerbation state, and the outcomes were assessed at the end of a 3-month cycle for response achievement based on the probability of treatment success with Acthar Gel. Patients may sustain the response or experience an exacerbation. For the base case scenario, moderate-to-severe SLE was defined as British Isles Lupus Assessment Group (BILAG)-2004 ≥ 20 or SLE Disease Activity Index 2000 (SLEDAI-2K) ≥ 10 and clinical response was based on SLE responder index (SRI)-4. Clinical response, productivity loss, and utility were derived from a phase 4 SLE trial; cost and disutility estimates were sourced from the literature. RESULTS: From a payer perspective, Acthar Gel versus SoC resulted in an incremental cost-effectiveness ratio (ICER) of $133,110 per quality-adjusted life-year (QALY) and $94,818 per QALY over 2 and 3 years, respectively. From a societal perspective, Acthar Gel versus SoC results in an ICER of $70,827 per QALY and $32,525 per QALY over 2 and 3 years, respectively. Results from the sensitivity and scenario analyses are consistent with those of the base case model. CONCLUSIONS: Acthar Gel is a cost-effective, value-based treatment option for appropriate patients with moderate-to-severe SLE at a willingness-to-pay threshold of $150,000 over 2-3 years from the US payer and societal perspectives. Acthar Gel results in the reduction of direct medical and indirect costs.

Temporal Changes in Cholangiocarcinoma Incidence and Mortality in the United States from 2001 to 2017.

BACKGROUND: Previous studies report increasing cholangiocarcinoma (CCA) incidence up to 2015. This contemporary retrospective analysis of CCA incidence and mortality in the US from 2001-2017 assessed whether CCA incidence continued to increase beyond 2015. PATIENTS AND METHODS: Patients (≥18 years) with CCA were identified in the National Cancer Institute Surveillance, Epidemiology, and End Results 18 cancer registry (International Classification of Disease for Oncology [ICD-O]-3 codes: intrahepatic [iCCA], C221; extrahepatic [eCCA], C240, C241, C249). Cancer of unknown primary (CUP) cases were identified (ICD-O-3: C809; 8140/2, 8140/3, 8141/3, 8143/3, 8147/3) because of potential misclassification as iCCA. RESULTS: Forty-thousand-and-thirty CCA cases (iCCA, n=13,174; eCCA, n=26,821; iCCA and eCCA, n=35) and 32,980 CUP cases were analyzed. From 2001-2017, CCA, iCCA, and eCCA incidence (per 100 000 person-years) increased 43.8% (3.08 to 4.43), 148.8% (0.80 to 1.99), and 7.5% (2.28 to 2.45), respectively. In contrast, CUP incidence decreased 54.4% (4.65 to 2.12). CCA incidence increased with age, with greatest increase among younger patients (18-44 years, 81.0%). Median overall survival from diagnosis was 8, 6, 9, and 2 months for CCA, iCCA, eCCA, and CUP. From 2001-2016, annual mortality rate declined for iCCA (57.1% to 41.2%) and generally remained stable for eCCA (40.9% to 37.0%) and for CUP (64.3% to 68.6%). CONCLUSIONS: CCA incidence continued to increase from 2001-2017, with greater increase in iCCA versus eCCA, whereas CUP incidence decreased. The divergent CUP versus iCCA incidence trends, with overall greater absolute change in iCCA incidence, provide evidence for a true increase in iCCA incidence that may not be wholly attributable to CUP reclassification.

Clinical and economic burden of major depressive disorder with acute suicidal ideation or behavior in a US Veterans Health Affairs database.

OBJECTIVE: Although a high incidence of major depressive disorder (MDD) and an increased risk of suicide are observed among the veteran population, there are yet limited real-world data characterizing patients with MDD with acute suicidal ideation/behavior (MDSI) in the Veterans Health Administration (VHA) system. We assessed the clinical and economic burden, including comorbidities, treatment patterns, health care resource utilization, and health care costs, among veterans and their family members with MDSI within the VHA system. METHODS: This retrospective, longitudinal analysis of VHA datasets (10/1/2015-3/31/2018) evaluated the clinical and economic burden associated with MDSI and compared this population with matched MDD alone (i.e. MDD diagnosis without acute suicidal ideation/behavior) and non-MDD (i.e. neither MDD nor acute suicidal ideation/behavior) cohorts. RESULTS: Among 11,203 patients with MDSI, the proportions of patients who filled a prescription for ≥1 antidepressant during the 12-month pre- and 6-month post-periods were significantly higher compared with patients with MDD alone (53.7% vs 28.8%, p < .05; and 72.3% vs 44.1%, p < .05; respectively). During the 12-month pre-period, the MDSI cohort had the highest proportion of patients with ≥1 mental health-related inpatient visit compared with the MDD alone and non-MDD cohorts (13.2% vs 2.3% vs 1.4%, respectively; p < .05), and the highest mental health-related costs per patient ($8853 vs $1913 vs $1079, respectively). For the 6-month post-period, the MDSI cohort had the highest proportion of patients with ≥1 mental health-related inpatient visit compared with the MDD alone and non-MDD cohorts (60.4% vs 7.9% vs 0.8%, respectively; p < .05), and had the highest mental health-related costs per patient ($20,334 vs $4803 vs $545, respectively). CONCLUSIONS: Findings demonstrate significant clinical and economic burden for those in the VHA system diagnosed with MDSI and highlight unmet needs and opportunities for improving the care of this vulnerable group.

There are limited real-world data regarding patients diagnosed with major depressive disorder and having suicidal thoughts/behavior (MDSI) in the Veterans Health Administration (VHA) system. We examined data on 11,203 patients with MDSI from the VHA between October 1, 2015 and March 31, 2018. We compared patients with MDSI with patients with major depressive disorder alone (MDD) and patients with no depression (non-MDD). Our results showed that patients with MDSI were treated with more antidepressant therapy, had more hospital stays (inpatient visits), and incurred greater costs than the MDD and non-MDD patients. These results highlight the unmet need and potential opportunity to improve patient care among veterans and their families with MDSI.

Understanding Predictors of Response to Repository Corticotropin Injection Treatment Among Patients With Advanced Symptomatic Sarcoidosis.

Background: Sarcoidosis, an inflammatory systemic granulomatous disease, affects multiple organs and has a diverse clinical course. Repository corticotropin injection (RCI) is an effective treatment for advanced symptomatic sarcoidosis. Since sarcoidosis affects patients differently, treatment response may vary by patient demographic, clinical, and treatment-related characteristics and physician specialty. However, there is a paucity of literature regarding predictors of sarcoidosis treatment response. Objectives: This study investigated predictors of response to RCI treatment. Methods: Post-hoc analysis was conducted using data from a previously published retrospective cross-sectional chart review study among symptomatic sarcoidosis patients ≥18 years of age previously treated with RCI. Outcome improvement 3 months post-RCI treatment was based on the clinician's subjective evaluation and analyzed using adjusted logistic regression. The most influential predictors for each outcome were based on statistical significance (P<.05) and the strength of the relationship assessed by the standardized ß coefficients. Results: The top predictors of outcome improvements were as follows. Global health assessment: (1) improvement in current health status influenced by complete RCI compliance, moderate overall symptom severity, and presence of extrapulmonary sites; and (2) improvement in overall symptoms influenced by age, shorter duration since sarcoidosis diagnosis, and complete RCI compliance. Clinical outcomes: (1) lung function improvement influenced by mild weight loss, mild wheezing/coughing, and non-African American race; (2) reduction in pulmonary fibrosis influenced by moderate overall symptom severity, mild wheezing/coughing, and mild weight loss; and (3) reduction in inflammation influenced by physician specialty, completing a course of RCI treatment, and moderate-to-severe night sweats. Patient-related outcomes: (1) reduction in fatigue influenced by physician specialty and moderate-to-severe fatigue; and (2) improvement in quality-of-life influenced by shorter duration since sarcoidosis diagnosis, moderate-to-severe wheezing/coughing, and complete RCI compliance. Corticosteroid discontinuation/reduction was influenced by physician specialty, moderate-to-severe shortness of breath, and comedication use before RCI. Conclusions: RCI may be a better treatment option for patients with more severe disease, primarily those presenting with symptoms. Complete compliance with RCI treatment may improve patients' health and quality of life. Understanding factors that influence RCI effectiveness across different treatment outcomes in real-world clinical practice is important for designing optimal sarcoidosis treatment strategies.

The current use and evolving landscape of nutraceuticals.

The nutraceutical market is currently a high-impact multi-billion-dollar industry, and it is anticipated to grow rapidly over the next decade. Nutraceuticals comprise diverse food-derived product categories that have become widespread due to increased consumer awareness of potential health benefits and the need for improved wellness. This targeted review is designed to identify the current global trends, market opportunities, and regulations that drive the nutraceutical industry. Safety and efficacy concerns are also explored with a view to highlighting areas that necessitate further research and oversight. Key drivers of the nutraceutical market include aging populations, consumer awareness, consumer lifestyle, increasing cost of healthcare, and marketing channels. Although some nutraceuticals hold promising preventive and therapeutic opportunities, there is a lack of a universal definition and regulatory framework among countries. Moreover, there is a lack of adequate evidence for their efficacy, safety, and effectiveness, which was even further highlighted during the ongoing coronavirus pandemic. Future prospective epidemiological studies can delineate the health impact of nutraceuticals and help set the scientific basis and rationale foundation for clinical trials, reducing the time and cost of trials themselves. Together, an understanding of the key drivers of the nutraceutical market alongside a consistent and well-defined regulatory framework will provide further opportunities for growth, expansion, and segmentation of nutraceuticals applications.

Cost-Effectiveness of Repository Corticotropin Injection for the Treatment of Acute Exacerbations in Multiple Sclerosis.

BACKGROUND: Relapses are common among patients with multiple sclerosis (MS) despite treatment with disease-modifying therapies. Repository corticotropin injection (RCI, Acthar® Gel), plasmapheresis (PMP), and intravenous immunoglobulin (IVIg) are alternative therapies for MS relapse. There is a dearth of economic assessments of these therapies for the acute exacerbations of MS. This study estimated the cost-effectiveness of RCI compared to PMP or IVIg. METHODS: A Markov state-transition model compared outcomes (costs, relapses, remission, and utilities) with RCI versus PMP or IVIg for the acute exacerbations in MS. The model was developed from the United States (US) payer and societal perspectives over one to three years. Patients initiated on alternative therapies were evaluated in one-day increments for the first 30 days during treatment. The model assumes the natural history of MS after treatment in the first month, adjusting for the effect of treatment. Incremental cost-effectiveness ratios (ICERs) were estimated as cost per quality-adjusted life-year (QALY) gained. The uncertainty in model parameters was evaluated in probabilistic sensitivity analyses. RESULTS: In the base case, RCI has an ICER of USD 42,078 per QALY compared to PMP over one year from the payer perspective and is dominant over two and three years; RCI is dominant compared to PMP from the societal perspective over all three years. Compared to IVIg, RCI is a dominant strategy from both payer and societal perspectives over all three years. Probabilistic sensitivity analysis supports the base case findings, suggesting that RCI may be cost-effective versus PMP and IVIg for acute exacerbations in MS. CONCLUSION: RCI is a cost-effective alternative treatment for MS relapses compared to PMP and IVIg from the US payer and societal perspectives.

Dose escalation and associated costs in biologic treatment of psoriasis based on real-world data.

OBJECTIVES: This study documents real-world patterns and additional costs of above-label (≥10% above the recommended maintenance dose) use of biologics in patients with plaque psoriasis. MATERIALS AND METHODS: This was a descriptive, retrospective cohort analysis using the IBM MarketScan Commercial and Medicare Supplemental Databases. Adult patients diagnosed with plaque psoriasis initiating treatment with etanercept, adalimumab, ixekizumab, or secukinumab between 1 January 2015 and 30 November 2019 (index) were eligible. Only biologics approved prior to 2017 were included to ensure data for all agents was available throughout the study period. Patients had no other indications for biologics of interest. Outcomes were measured in the 12-month follow-up period after start of maintenance dosing. RESULTS: Of 6453 patients included, 708 (11.0%) received etanercept, 4654 (72.1%) received adalimumab, 228 (3.5%) received ixekizumab, and 863 (13.4%) received secukinumab. Above-label dosing was recorded in 326 (46.0%) patients receiving etanercept, 513 (11.0%) receiving adalimumab, 40 (17.5%) receiving ixekizumab, and 79 (9.2%) receiving secukinumab. Mean time to above-label use for all treatments was 50.7-99.5 days; the median was 21-37 days. Mean duration of above-label use for all treatments was 130-196 days; the median was 35-175 days. Mean total additional annual psoriasis-related medical/pharmacy costs associated with above-label use were $312/$16,475 for etanercept, $278/$9,773 for adalimumab, $124/$5,202 for ixekizumab, and $277/$9,288 for secukinumab. Above-label use was generally not associated with safety concerns; however, gastrointestinal and combined "other" nonrespiratory infections were significantly more frequent in patients receiving adalimumab above-label. CONCLUSIONS: Above-label use of biologics for psoriasis treatment was most frequent for patients receiving etanercept, followed by ixekizumab, adalimumab, and secukinumab. Above-label vs on-label use resulted in additional costs but few significant safety concerns.

Cost-Effectiveness of Repository Corticotropin Injection versus Standard of Care for the Treatment of Active Rheumatoid Arthritis.

INTRODUCTION: Patients with active rheumatoid arthritis (RA) often have inadequately controlled symptoms and are unable to achieve remission or low disease activity despite aggressive treatment. This results in irreversible joint damage, adversely affecting patients' physical and social functioning. The objective was to estimate the cost-effectiveness of repository corticotropin injection (RCI) versus standard of care (SoC) in patients with active RA from the United States (US) payer and societal perspectives over two to three years. METHODS: An individual-level microsimulation was developed to generate individual trajectories for patients with RA, using data from a published Phase 4 trial of RCI. These trajectories report a patient's disease pathway and associated cost and quality-of-life outcomes. The incremental cost-effectiveness ratio (ICER) of RCI versus SoC was assessed using the literature-derived direct medical and indirect costs, and quality-adjusted life-years (QALY) derived from a Phase 4 trial of RCI. The uncertainty in base case estimates of the parameters was evaluated in the sensitivity analysis. RESULTS: Over two years, RCI has an incremental QALY gain of 1.591 and incremental cost of $183,965 and $117,443 from payer and societal perspective, respectively, resulting in an ICER of $115,629/QALY and $73,817/QALY compared to SoC. Over three years, RCI has an incremental QALY gain of 2.336 and incremental cost of $202,315 and $104,506 from payer and societal perspective, respectively, resulting in an ICER of $86,607/QALY and $44,737/QALY compared to SoC. Results from the probabilistic sensitivity analysis are consistent with those of the base case model. CONCLUSION: RCI is a cost-effective strategy for patients with persistently active RA who are previously treated with disease-modifying anti-rheumatic drugs and corticosteroids compared to SoC over two to three years from the payer and societal perspectives at a US willingness-to-pay threshold of $150,000/QALY. Further, the economic benefit of RCI is realized with improvement in a patient's clinical and health outcomes.

A Systematic Literature Review and Indirect Treatment Comparison of Efficacy of Repository Corticotropin Injection versus Synthetic Adrenocorticotropic Hormone for Infantile Spasms.

Background: Infantile spasms is a rare disease characterized by distinct seizures and hypsarrhythmia. Adrenocorticotropic hormone (ACTH) is available as a natural product (repository corticotropin injection, [RCI]; Acthar® Gel) and as synthetic analogs. RCI is a naturally-sourced complex mixture of purified ACTH analogs and other pituitary peptides approved by the United States Food and Drug Administration as a monotherapy for the treatment of infantile spasms. RCI is commonly used in the United States. Outside the United States, synthetic analogs of ACTH-synthetic ACTH1-24 (tetracosactide) and synthetic ACTH1-39 (corticotropin carboxymethyl-cellulose [CCMC])-are used. The efficacy of RCI may differ from that of synthetic ACTH treatments based on the structure of peptide; however, no head-to-head clinical trials have compared the efficacy of RCI and synthetic ACTH treatments. Objective: A systematic review and indirect treatment comparison of clinical trials was conducted to assess the comparative efficacy of RCI and synthetic ACTH treatments in infantile spasms. Methods: A search was conducted in MEDLINE, EMBASE, and Cochrane databases through September 30, 2020. Relevant clinical trials on RCI or synthetic ACTH therapy and reporting either cessation of spasms or resolution of hypsarrhythmia, separately or as a combined outcome were included. A Bayesian indirect treatment comparison using a fixed-effects model was used for comparative efficacy. Results: Of 473 citations screened, 21 studies were reviewed qualitatively. In the indirect treatment comparison of six eligible clinical trial studies, the odds of achieving efficacy outcomes were five to eight times greater with RCI than with tetracosactide and 14 to 16 times greater than CCMC. This translated to a risk reduction of 10% to 14% and 40% to 50% with RCI versus tetracosactide and CCMC, respectively. For every two to five patients treated, RCI improved efficacy outcomes in one additional patient compared to synthetic ACTH (adjusted number needed-to-treat). Conclusions: Based on the available limited evidence, results suggest RCI may be more efficacious for infantile spasms than synthetic ACTH treatments. Our findings provide a blueprint to inform the design of future prospective studies for the treatment of infantile spasms.

The Prevalence and Incidence of Dry Eye Disease Among Patients Using Continuous Positive Airway Pressure or Other Nasal Mask Therapy Devices to Treat Sleep Apnea.

INTRODUCTION: Dry eye disease (DED) prevalence is estimated at 9.3% of the US adult population, although diagnosed rate is much lower. This study examined real-world incidence rates (IR) and prevalence rates (PR) of DED in adults using continuous positive airway pressure (CPAP) or nasal mask therapy (NMT) devices to treat sleep apnea. METHODS: Using IBM MarketScan Commercial and Medicare Supplemental claims databases, this study identified adults with ≥1 claim of CPAP or other NMT device between January 1, 2014 and June 30, 2018, ≥1 diagnosis of sleep apnea during a 12-month pre-index period, and continuous benefit enrollment ≥12 pre- and post-index date. The date of the first CPAP or NMT device claim was considered the index date. Descriptive analyses included PR, IR, and IR per 100-person years (100PY) for the overall population and subgroups including age, sex, and baseline comorbidities. RESULTS: The 1-, 2-, and 3-year PR of DED was 6.2%, 10.0%, and 13.0%, while the IR of DED was 4.0%, 7.3%, and 10.3%, respectively. Females had a higher IR of DED compared to males: 5.8%, 10.8%, and 15.1% vs 3.0%, 5.4%, and 7.9%, respectively. DED increased with age with a 1-, 2-, and 3-year PR for patients aged 18-24 years of 2.2%, 3.4%, and 5.0% vs 17.6%, 25.8%, and 32.1% in patients aged ≥75, respectively. Overall, IR per 100PY of DED was 3.68, higher for females than males (5.51 vs 2.73). PR and IR of DED were high among patients with comorbid inflammatory or metabolic conditions. CONCLUSION: The PR and IR of DED in CPAP or NMT users were higher than the reported prevalence of DED in the general population. CPAP/NMT users who were female, older, or had comorbid inflammatory or metabolic conditions may experience a higher incidence and prevalence of DED.

Phosphodiesterase Type-5 Inhibitor Prescription Patterns in the United States Among Men With Erectile Dysfunction: An Update.

BACKGROUND: While phosphodiesterase type-5 inhibitors (PDE5Is) are highly effective for the treatment of erectile dysfunction (ED) and well tolerated, updated data on prescription patterns have been limited in real-world settings. AIM: To describe men in the United States who are prescribed PDE5Is for ED treatment and to evaluate patterns of initiation, switching, and treatment overlap. METHODS: This retrospective claims study used MarketScan Commercial and Medicare Supplement Databases from January 1, 2010, to December 31, 2015, to identify initial PDE5I claims (index date) for sildenafil, tadalafil, and/or vardenafil. Adults aged ≥18 years with ED were identified between July 1, 2010, and December 31, 2014, allowing for a 6-month preindex and 12-month follow-up period from the index date. OUTCOMES: Outcomes included patient demographics and treatment-related patterns after treatment initiation. RESULTS: A total of 106,206 identified patients met all inclusion criteria. Of these, 51,694, 40,193, and 14,319 had initial claims for sildenafil, tadalafil, and vardenafil, respectively. Mean age was 50.35 years, and comorbidities included dyslipidemia (44.17%), hypertension (43.09%), diabetes (15.32%), and depression (10.61%). More patients (48.67%) initiated on sildenafil than tadalafil (37.85%) or vardenafil (13.48%). Rate of switching was lower in the 60 days after the end of day supply of the initial prescription in the sildenafil cohort (2.71%) compared with the tadalafil (2.81%) and vardenafil (3.88%) cohorts (P < .001 for sildenafil vs tadalafil or vardenafil). Treatment overlap was lower in the sildenafil cohort (0.35%) than in the tadalafil (0.75%) and vardenafil (0.62%) groups (P < .001 for sildenafil vs tadalafil or vardenafil). CLINICAL IMPLICATIONS: These findings provide insight into updated patterns of PDE5I prescriptions in the United States and may aid in clinical decision-making. STRENGTHS & LIMITATIONS: Strengths include the large sample size, long data coverage period, and the real-world nature of the study. Limitations include the retrospective study design, use of data collected with a primary focus of claims, and lack of further details regarding reasons that drive switching. Actual rates of ED and impact on prescription patterns may be underestimated because the claims database only captured patients electing to visit a health-care provider. CONCLUSION: Among men with ED in the United States, rates of switching and treatment overlap were low for all PDE5Is but were found to be the lowest for sildenafil compared with tadalafil and vardenafil. Mulhall JP, Chopra I, Patel D, et al. Phosphodiesterase Type-5 Inhibitor Prescription Patterns in the United States Among Men With Erectile Dysfunction: An Update. J Sex Med 2020;17:941-948.

Cost per response analysis of repository corticotropin injection versus other alternative treatments for acute exacerbations of multiple sclerosis.

BACKGROUND: Relapses are common in patients with multiple sclerosis (MS) even after the use of disease-modifying therapies. Repository corticotropin injection (RCI), plasmapheresis (PMP), and intravenous immunoglobulin (IVIg) may be utilized as alternative therapies in the management of MS relapse. There is a lack of health economic studies on these alternative therapies for the acute exacerbations of MS. The objective of this study was to estimate the cost per response of RCI compared with PMP or IVIg from the United States (US) commercial payer perspective. METHODS: Costs and response rates were sourced from published peer-reviewed observational studies. The cost of care included MS-related inpatient, outpatient, and medication costs. Treatment response was defined as no evidence of additional relapse treatment or procedure claims within 30 days after treatment. The cost per response for each treatment was calculated by dividing the total annual cost of care by the proportion of patients with resolved relapse for each treatment. The incremental cost per response ratio was calculated by dividing the difference in costs and the proportion of responses for RCI versus PMP or IVIg. One-way sensitivity analysis (OWSA) was conducted for both costs and response rates. All included costs were inflated to the 2019 US dollars. RESULTS: With a lower total annual cost of care and a higher response rate, RCI had a lower cost per response (US$141,970) compared with PMP or IVIg (US$253,331). RCI had a lower cost per response even when more stringent estimates for RCI were applied in the OWSA. The annual cost of care had a greater influence on the cost per response in the OWSA. CONCLUSIONS: Based on the estimates from the real-world evidence, our economic evaluation suggests that RCI may have real-world clinical and economic benefits for patients with MS relapse who fail on corticosteroid therapy.

Repository corticotropin injection in patients with advanced symptomatic sarcoidosis: retrospective analysis of medical records.

BACKGROUND: Repository corticotropin injection (RCI) has regulatory approval for many indications, including symptomatic sarcoidosis. This large case series of patients with advanced symptomatic sarcoidosis treated with RCI describes patient characteristics, RCI utilization patterns, concomitant therapies, and physicians' assessments of treatment response. METHODS: Patients ⩾18 years with symptomatic sarcoidosis, treated with RCI in the previous 36 months, who had completed a course of RCI or received RCI for ⩾6 months at the time of data collection were included. RESULTS: The study included 302 patients (mean age, 51 years; 52%, women) with a mean 4.8 years since initial diagnosis of sarcoidosis. Most patients (76%) had extrapulmonary involvement, primarily in the skin (28%), joints (25%), heart (22%), and eyes (22%); 34% had multiple (⩾2) organ involvement. The mean duration of RCI treatment was 32.5 weeks, with 61.6% of patients continuing RCI therapy for ⩾6 months. The RCI utilization pattern indicated an individualized approach to therapy, with a higher starting dose associated with a shorter duration of therapy compared with a lower starting dose. The percentage of patients who used corticosteroids decreased from 61.3% during the 3 months before initiation of RCI to 12.9% 3 months after RCI therapy; the mean daily dose of corticosteroid decreased from 18.2 mg to 9.9 mg. The proportion of patients given <10 mg/day of prednisone increased from 21% before RCI use to 47% 3 months after RCI use. According to physicians' assessments of change in patients' health status after RCI therapy, overall status improved in 95% of patients, overall symptoms in 73%, lung function in 38%, and inflammation in 33%. CONCLUSIONS: The findings suggest that RCI is a viable treatment option for patients with advanced symptomatic sarcoidosis and provide insights on patient characteristics and practice patterns to help clinicians determine appropriate use. The reviews of this paper are available via the supplemental material section.

Novel Diphenylamine Analogs Induce Mesenchymal to Epithelial Transition in Triple Negative Breast Cancer.

Epithelial to mesenchymal transition (EMT) is a cellular program that converts non-motile epithelial cells into invasive mesenchymal cells. EMT is implicated in cancer metastasis, chemo-resistance, cancer progression, and generation of cancer stem cells (CSCs). Inducing mesenchymal to epithelial transition (MET), the reverse phenomenon of EMT, is proposed as a novel strategy to target triple negative and tamoxifen-resistant breast cancer. Triple negative breast cancer (TNBC) is characterized by the loss of hormone receptors, a highly invasive mesenchymal phenotype, and a lack of targeted therapy. Estrogen receptor-positive breast cancer can be targeted by tamoxifen, an ER antagonist. However, these cells undergo EMT over the course of treatment and develop resistance. Thus, there is an urgent need to develop therapeutic interventions to target these aggressive cancers. In this study, we examined the role of novel diphenylamine analogs in converting the mesenchymal phenotype of MDA-MB-231 TNBC cells to a lesser aggressive epithelial phenotype. Using analog-based drug design, a series of diphenylamine analogs were synthesized and initially evaluated for their effect on E-cadherin protein expression and changes incell morphology, which was quantified by measuring the spindle index (SI) value. Selected compound 1 from this series increases the expression of E-cadherin, a primary marker for epithelial cells, and decreases the mesenchymal markers SOX2, ZEB1, Snail, and vimentin. The increase in epithelial markers and the decrease in mesenchymal markers are consistent with a phenotypic switch from spindle-like morphology to cobblestone-like morphology. Furthermore, Compound 1 decreases spheroid viability, cell migration, and cell proliferation in triple negative BT-549 and tamoxifen-resistant MCF-7 breast cancer cells.

Evaluation of waste anesthetic gas surveillance program and isoflurane exposures during animal and human surgery.

Prolonged occupational exposure to waste anesthetic gases may have the potential to cause adverse health effects. Workplace exposure surveillance programs are intended to reduce health risk by evaluating exposures to waste anesthetic gases during surgical procedures. Both the personal breathing-zone and area measurements are used to assess occupational exposure in the operating theater. Direct-reading instruments provide real-time measurements and are useful for identifying leaks and evaluating on-the-spot corrective actions. Passive diffusion monitors quantify occupational exposures over time during surgery. The aim of this study was to evaluate a waste anesthetic gas surveillance program to understand occupational exposures and further improve data collection strategy. For this study, 76 survey reports from 2012 through 2014 were retrospectively reviewed to assess occupational exposures to isoflurane in 58 unique procedural rooms operated by the National Institutes of Health. The surveys included industrial hygiene assessments performed during animal and human surgical procedures. The survey reports were evaluated qualitatively and data from these reports was transcribed for quantitative analysis. Variations in sample strategy were observed between surveys and were attributed to ambiguity in the written surveillance program. The study also evaluated the relationship between isoflurane concentrations and sampling method, sampling location, patient type, or scavenging method. Isoflurane exposures were significantly higher among procedures performed on rodents compared to the patients with a large body mass (humans, non-human primates, and swine) (P < 0.05) and in procedures using the charcoal canister exhaust system compared with the central vacuum exhaust system. In addition, individuals performing the surgical procedure experienced elevated occupational exposures measured by both direct-reading instrument and passive diffusion monitors, that is, exposure was significantly higher as measured at the breathing-zone compared with any area within the room (P < 0.05). The study identified several inconsistencies and shortcomings in the surveillance program. Isoflurane concentrations measured during rodent procedures requires further review of work practices and engineering controls. Overall, the findings provide insights to further improve data collection, monitoring, and control of isoflurane exposures.

Impact of Incident Cancer on Short-Term Coronary Artery Disease-Related Healthcare Expenditures Among Medicare Beneficiaries.

Background: Healthcare spending for coronary artery disease (CAD)-related services is higher than for other chronic conditions. Diagnosis of incident cancer may impede management of CAD, thereby increasing the risk of CAD-related complications and associated healthcare expenditures. This study examined the relationship between incident cancer and CAD-related expenditures among elderly Medicare beneficiaries. Patients and Methods: A retrospective longitudinal study was conducted using the SEER-Medicare linked registries and a 5% noncancer random sample of Medicare beneficiaries. Elderly fee-for-service Medicare beneficiaries with preexisting CAD and with incident breast, colorectal, or prostate cancer (N=12,095) or no cancer (N=34,237) were included. CAD-related healthcare expenditures comprised Medicare payments for inpatient, home healthcare, and outpatient services. Expenditures were measured every 120 days during the 1-year preindex and 1-year postindex periods. Adjusted relationship between incident cancer and expenditures was analyzed using the generalized linear mixed models. Results: Overall, CAD-related mean healthcare expenditures in the preindex period accounted for approximately 32.6% to 39.5% of total expenditures among women and 41.5% to 46.8% among men. All incident cancer groups had significantly higher CAD-related expenditures compared with noncancer groups (P<.0001). Men and women with colorectal cancer (CRC) had 166% and 153% higher expenditures, respectively, compared with their noncancer counterparts. Furthermore, men and women with CRC had 57% and 55% higher expenditures compared with those with prostate or breast cancer, respectively. Conclusions: CAD-related expenditures were higher for elderly Medicare beneficiaries with incident cancer, specifically for those with CRC. This warrants the need for effective programs and policies to reduce CAD-related expenditures. Close monitoring of patients with a cancer diagnosis and preexisting CAD may prevent CAD-related events and expenditures.