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Clinicopathologic characteristics of bladder cancer patient samples in microarray datasets

Supplemental Figure Legends

List of all differentially regulated probes with AGL loss in UMUC3 bladder cancer cells at FDR at 2%.

Multivariable analysis corresponding to Figure 6C (iii)

Purpose: We demonstrated that amylo-alpha-1-6-glucosidase-4-alpha-glucanotransferase (AGL) is a tumor growth suppressor and prognostic marker in human bladder cancer. Here we determine how AGL loss enhances tumor growth, hoping to find therapeutically tractable targets/pathways that could be used in patients with low AGL–expressing tumors.Experimental Design: We transcriptionally profiled bladder cell lines with different AGL expression. By focusing on transcripts overexpressed as a function of low AGL and associated with adverse clinicopathologic variables in human bladder tumors, we sought to increase the chances of discovering novel therapeutic opportunities.Results: One such transcript was hyaluronic acid synthase 2 (HAS2), an enzyme responsible for hyaluronic acid (HA) synthesis. HAS2 expression was inversely proportional to that of AGL in bladder cancer cells and immortalized and normal urothelium. HAS2-driven HA synthesis was enhanced in bladder cancer cells with low AGL, and this drove anchorage-dependent and independent growth. siRNA-mediated depletion of HAS2 or inhibition of HA synthesis by 4-methylumbelliferone (4MU) abrogated in vitro and xenograft growth of bladder cancer cells with low AGL. AGL and HAS2 mRNA expression in human tumors was inversely correlated in patient datasets. Patients with high HAS2 and low AGL tumor mRNA expression had poor survival, lending clinical support to xenograft findings that HAS2 drives growth of tumors with low AGL.Conclusions: Our study establishes HAS2-mediated HA synthesis as a driver of growth of bladder cancer with low AGL and provides preclinical rationale for personalized targeting of HAS2/HA signaling in patients with low AGL–expressing tumors. Clin Cancer Res; 22(5); 1274–83. ©2015 AACR.

Supplemental Figure 1. Heatmap for top 100 differentially expressed genes with AGL depletion in bladder cancer cell line UMUC3. Supplemental Figure 2. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for HAS2, RRAGD, VCAN, EREG and TULP3 in T24T cells with or without AGL. Supplemental Figure 3. A,B,C, Monolayer growth of UMUC3 cells with and without AGL knockdown followed by knockdown of HAS2, RRAGD and TULP3. Supplemental Figure 4. A, qRT-PCR for HAS2 in UMUC3 control and AGL knockdown cells using a second siRNA against HAS2 followed by monolayer growth assay. B, qRT-PCR for HAS2 in MGHU4 cells with AGL knockdown. C, qRT-PCR to validate knockdown of HAS2 in MGHU4 control and AGL knockdown cells followed by monolayer growth assay. Supplemental Figure 5. A, HA ELISA for UMUC3 AGL knockdown cells after knockdown of HAS2 using a new siRNA. B, HA ELISA of MGHU4 cells with or without AGL expression after HAS2 knockdown. C, Monolayer growth of T24T cells with and without AGL on treatment with 4MU. D, Monolayer growth of T24T cells with and without AGL on treatment with 4MU and HA.

Multivariable analysis corresponding to Figures 6C (i) and (ii)

BACKGROUND: Opioid use after surgery is associated with increased health care utilization and costs. Although some studies show that surgical patients may later become persistent opioid users, data on the association between new persistent opioid use after surgery and health care utilization and costs are lacking. OBJECTIVE: To compare health care utilization and costs after major inpatient or METHODS: The IBM MarketScan Research databases were used to identify opioid-naive patients with major inpatient or outpatient surgeries and at least 1 year of continuous enrollment before and after this index surgery. Cohorts were stratified by new persistent opioid utilization status, setting of surgery (inpatient, outpatient), and payer (commercial, Medicare, Medicaid). Patients were considered new persistent opioid users if they had at least 1 opioid claim 4-90 days after index surgery and at least 1 opioid claim 91-180 days after index surgery. Patients with opioid prescription claims between 1 year and 15 days before their index event were excluded. Health care utilization and costs (excluding index surgery) were measured in the 1-year period after surgery. Predicted costs and cost ratios were estimated using multivariable log-linked gamma-family generalized linear models. RESULTS: In the inpatient cohorts, 827,583 commercial, 186,154 Medicare, and 104,734 Medicaid patients were included in the study, and the incidence of new persistent opioid use in these cohorts was 4.1%, 5.6%, and 7.1%, respectively. In the outpatient cohorts, 1,542,565 commercial, 390,876 Medicare, and 94,878 Medicaid patients were selected, with 2.0%, 1.5%, and 6.4% new persistent opioid use, respectively. Across all 3 payers in both surgical settings, patients with new persistent opioid use had a higher comorbidity burden and more use of concomitant medications in the baseline period. In the 1-year period after index surgery, patients with new persistent opioid use had more inpatient admissions, emergency department visits, and ambulance/paramedic service use than patients without persistent use, regardless of payer and setting. Patients with new persistent opioid use had approximately 5 times more opioid prescriptions and also had more nonopioid pharmacy claims than those without persistent use across all cohorts. After covariate adjustment, predicted 1-year total health care costs were significantly higher for patients with new persistent opioid use compared with those without persistent use for all comparisons (commercial inpatient: $29,499 vs. $11,798; Medicare inpatient: $34,455 vs. $21,313; Medicaid inpatient: $14,622 vs. $6,678; commercial outpatient: $18,751 vs. $7,517; Medicare outpatient ($26,411 vs. $13,577; Medicaid outpatient: $12,381 vs. $6,784; all P < 0.001). CONCLUSIONS: New persistent opioid use after major surgery in opioid-naive patients is associated with increased health care utilization and costs in the year after surgery across all surgical settings and payers. DISCLOSURES: Funding for this study was provided by Heron Therapeutics, which participated in analysis and interpretation of data, drafting, reviewing, and approving the publication. All authors contributed to the analysis and interpretation of the data and development of the publication and maintained control over the final content. England and Evans-Shields are employees of Heron Therapeutics. Kong, Lew, Zimmerman, and Henriques are employees of IBM Watson Health, which was compensated by Heron Therapeutics for conducting this research. Brummett is a paid consultant for Heron Therapeutics, Vertex Pharmaceuticals, and Alosa Health and provides expert testimony. He further reports receipt of research funding from MDHHS (Sub K Michigan Open), NIDA (Centralized Pain Opioid Non-Responsiveness R01 DA038261-05), NIH0DHHS-US-16 PAF 07628 (R01 NR017096-05), NIH-DHHS (P50 AR070600-05 CORT), NIH-DHHS-US (K23 DA038718-04), NIH-DHHS-US-16-PAF06270 (R01 HD088712-05), NIH-DHHS-US-17-PAF02680 (R01 DA042859-05), and UM Michigan Genomics Initiative and holds a patent for peripheral perineural dexmedetomidine. Sun reports funding from the National Institute on Drug Abuse (K08DA042314) as well as consulting fees from the Mission Lisa Foundation that are unrelated to this work.

The aim of this study was to compare healthcare costs between ixekizumab (IXE)-treated and secukinumab (SEC)-treated patients with psoriasis over a 24-month follow-up period in the United States.Patients with psoriasis diagnosis were identified from IBM Watson Health MarketScanOverall, 1461 patients (IXE users, n = 471; SEC users, n = 990) were included. IXE versus SEC users had higher weighted PPPM all-cause, psoriasis-related, and index drug costs (p ≤ 0.001). IXE versus SEC users had comparable ICER-adjusted mean PPPM all-cause costs (US$4172 ± 3349 vs US$3978 ± 2619; p = 0.227) and psoriasis-related costs (US$2950 ± 1332 vs US$2899 ± 1152; p = 0.447). After applying ICER and adherence adjustments, index drug costs were similar between IXE and SEC users (US$3794 ± 1822 vs US$3766 ± 1973; p = 0.795).All-cause and psoriasis-related costs were comparable between IXE and SEC users after ICER adjustments; index drug costs were similar after ICER and adherence adjustments.

Real-world data on treatment patterns associated with use of interleukin-17A inhibitors in psoriasis are lacking.To compare treatment patterns between ixekizumab or secukinumab users in clinical practice.A retrospective cohort study included patients with psoriasis aged ≥18 years treated with ixekizumab or secukinumab between March 1, 2016, and May 31, 2018 in IBM MarketScan (IBM Corp, Armonk, NY) databases. Inverse probability of treatment weighting and multivariable models were used to address cohort imbalances and estimate the risks of nonpersistence (60-day gap), discontinuation (≥90-day gap), switching, and the odds of adherence.The study monitored 645 ixekizumab users for 13.7 months and 1152 secukinumab users for 16.3 months. Ixekizumab users showed higher persistence rate (54.8% vs 45.1%, P .001) and lower discontinuation rate (37.8% vs 47.5%, P .001) than secukinumab. After multivariable adjustment, ixekizumab users had lower risks of nonpersistence (hazard ratio, 0.82; 95% confidence interval, 0.71-0.95) and discontinuation (hazard ratio, 0.82; 95% confidence interval, 0.70-0.96), and higher odds of high adherence to treatment measured by a medication possession ratio ≥80% (hazard ratio, 1.31; 95% confidence interval, 1.07-1.60). The risk of switching was similar between cohorts.Disease severity and clinical outcomes were unavailable.Ixekizumab users demonstrated longer drug persistence, lower discontinuation rate and risk of discontinuation, higher likelihood of adherence, and similar risk of switching compared with secukinumab users in clinical practices.

To compare long-term healthcare resource utilization (HCRU) and costs among patients who initiated ixekizumab (IXE) or adalimumab (ADA) for treatment of psoriasis in the United States.Adult patients with psoriasis who had ≥1 claim for IXE or ADA were identified from IBM MarketScan claims databases prior to the COVID-19 pandemic (1 March 2016-31 October 2019). The index date was the date of first claim for the index drug of interest. Inverse probability of treatment weighting was employed to balance treatment cohorts. All-cause and psoriasis-related HCRU and costs were examined for 24 months of follow-up. Costs were reported as per patient per month. Costs of psoriasis-related biologics were adjusted using published Institute for Clinical and Economic Review (ICER) discount factors. Index drug costs were adjusted for adherence and ICER discount rates.The analyses included 407 IXE and 2,702 ADA users. IXE users had significantly higher inpatient admission rate (all-cause HCRU: 14.9% vs. 11.0%;Study relied on administrative claims data, subjected to data coding limitations and data entry errors. Rebates, patient assistance programs, and commission to wholesalers are not always captured in claims. Adjustment made by ICER discount factors may lead to double-discounting if the discounts have been applied in claim payments.All-cause HCRU was higher in IXE than ADA users. Healthcare costs were also higher in IXE than ADA users after ICER adjustment, over 24 months. Cost differences were largely driven by higher treatment adherence associated with IXE. Index drug costs were comparable after ICER and adherence adjustments.

Background There is lack of real-world treatment pattern comparison data between ixekizumab and adalimumab which are approved for the treatment of moderate-to-severe plaque psoriasis. Objective To compare real-world treatment patterns among psoriasis patients initiating ixekizumab or adalimumab in the United States. Methods Psoriasis patients with ≥1 claim for ixekizumab or adalimumab between March 1, 2016, and May 31, 2018, were identified (index date = date of first ixekizumab or adalimumab claim) from the IBM Watson Health MarketScan® databases. Patients were required to be continuously enrolled for ≥12 months before the index date and followed for a minimum of 6 months until inpatient death, enrollment end, or study end, whichever occurred first. Treatment persistence, adherence, discontinuation, restart, and switching were analyzed. Inverse probability of treatment weighting and multivariable regression modeling were employed to address cohort imbalances and estimate the adjusted risk of non-persistence, discontinuation, and switching, and the odds of adherence. Results A total of 646 ixekizumab and 3668 adalimumab users were included and followed for a mean of 14.0 and 16.5 months, respectively. Compared to adalimumab, ixekizumab was associated with 19% lower risk of non-persistence (hazard ratio [HR]=0.81, 95% confidence interval [CI]: 0.69-0.95), 26% lower risk of discontinuation (HR=0.74, 95% CI: 0.62-0.88), and 28% lower risk of switching (HR=0.72, 95% CI: 0.57-0.91). Ixekizumab users had higher odds of medication possession ratio ≥80% (odds ratio [OR]=1.36, 95% CI: 1.10-1.69) but similar odds by proportion of days covered ≥80% (OR=1.22, 95% CI: 0.98-1.53). Conclusion Psoriasis patients treated with ixekizumab demonstrated longer persistency, higher adherence and were less likely to discontinue or switch treatment compared to adalimumab users. However, while patients achieving highly adherent threshold significantly differed by MPR ≥80%, it did not by PDC ≥80%; hence, further analysis using fixed-length follow-up is required.

The treatment of postsurgical pain with prescription opioids has been associated with persistent opioid use and increased health care utilization and costs.To compare the health care burden between opioid-naive adult patients who were prescribed opioids after a major surgery and opioidnaive adult patients who were not prescribed opioids.Administrative claims data from the IBM Watson Health MarketScan Research Databases for 2010-2016 were used. Opioid-naive adult patients who underwent major inpatient or outpatient surgery and who had at least 1 year of continuous enrollment before and after the index surgery date were eligible for inclusion. Cohorts were defined based on an opioid pharmacy claim between 7 days before index surgery and 1 year after index surgery (opioid use during surgery and inpatient use were not available). To ensure an opioid-naive population, patients with opioid claims between 365 and 8 days before surgery were excluded. Acute medical outcomes, opioid utilization, health care utilization, and costs were measured during the post-index period (index surgery hospitalization and day of index outpatient surgery not included). Predicted costs were estimated from multivariable log-linked gamma-generalized linear models.The final sample consisted of 1,174,905 opioid-naive patients with an inpatient surgery (73% commercial, 20% Medicare, 7% Medicaid) and 2,930,216 opioid-naive patients with an outpatient surgery (74% commercial, 23% Medicare, and 3% Medicaid). Opioid use after discharge was common among all 3 payer types but was less common among Medicare patients (63% inpatient/43% outpatient) than patients with commercial (80% inpatient/75% outpatient) or Medicaid insurance (86% inpatient/81% outpatient). Across all 3 payers, opioid users were younger, were more likely to be female, and had a higher preoperative comorbidity burden than nonopioid users. In unadjusted analyses, opioid users tended to have more hospitalizations, emergency department visits, and pharmacy claims. Adjusted predicted 1-year post-period total health care costs were significantly higher (Filling an outpatient opioid prescription (vs. no opioid prescription) in the 1 year after inpatient or outpatient surgery was associated with increased health care utilization and costs across all payers.Funding for this study was provided by Heron Therapeutics, which participated in analysis and interpretation of data, drafting, reviewing, and approving the publication. All authors contributed to the development of the publication and maintained control over the final content. Brummett is a paid consultant for Heron Therapeutics and Recro Pharma and reports receipt of research funding from MDHHS (Sub K Michigan Open), NIDA (Centralized Pain Opioid Non-Responsiveness R01 DA038261-05), NIH0DHHS-US-16 PAF 07628 (R01 NR017096-05), NIH-DHHS (P50 AR070600-05 CORT), NIH-DHHS-US (K23 DA038718-04), NIH-DHHS-US-16-PAF06270 (R01 HD088712-05), NIH-DHHS-US-17-PAF02680 (R01 DA042859-05), and UM Michigan Genomics Initiative and holding a patent for peripheral perineural dexmedetomidine. Oderda is a paid consultant for Heron Therapeutics. Pawasauskas is a paid consultant to Heron Therapeutics and Mallinckrodt Pharmaceuticals. England and Evans-Shields are employees of Heron Therapeutics. Kong, Lew, Zimmerman, and Henriques are employees of IBM Watson Health, which was compensated by Heron Therapeutics for conducting this research. Portions of this work were presented as a poster at the AMCP Managed Care and Specialty Pharmacy Annual Meeting 2019; March 25-28, 2019; San Diego, CA.

Introduction Real-world data comparing effectiveness of ixekizumab (IXE) and secukinumab (SEC) among biologic-experienced patients are limited. This study compared treatment patterns over 18 months among biologic-experienced patients with psoriasis receiving IXE or SEC in the USA. Methods A retrospective observational study using administrative claims data from IBM® Watson Health MarketScan® Research Databases included adult patients with ≥ 1 inpatient or ≥ 2 non-diagnostic (≥ 30 days apart) outpatient claim/s with diagnosis of psoriasis between March 1, 2015 and October 31, 2019, and ≥ 1 claim/s for index drugs, IXE or SEC, between March 1, 2016 and October 31, 2019. Patients had to have ≥ 1 claim/s for biologics indicated for psoriasis in the 6-month pre-period. During the 18-month follow-up, treatment adherence (proportion of days covered [PDC]), high adherence (PDC ≥ 80%), persistence, discontinuation, reinitiation, and switching were assessed. To address cohort imbalances, inverse probability of treatment weighting was employed. Logistic regression was used to estimate odds ratio for high adherence. Cox proportional hazard models were used to estimate hazard ratio for non-persistence, discontinuation, and switching. Results Overall, 411 IXE and 780 SEC users were included. After weighting, IXE users had significantly higher rate of high treatment adherence (42% vs. 35%, p = 0.019), higher persistence rate (44.9% vs. 36.9%, p = 0.007), lower discontinuation rate (48.4% vs. 56.0%, p = 0.012), and lower switching rate (26.6% vs. 34.0%, p = 0.009) compared with SEC users. After multivariable adjustment, compared with SEC, IXE use was associated with 36% higher odds of high treatment adherence (OR 1.36, 95% CI 1.05–1.74), 20% lower risk of treatment non-persistence (HR 0.80, 95% CI 0.68–0.93), 19% lower risk of discontinuation (HR 0.81, 95% CI 0.68–0.96), and 25% lower risk of switching (HR 0.75, 95% CI 0.60–0.93). Conclusion This study suggests that IXE treatment is associated with significantly higher adherence rates and significantly lower non-persistence, discontinuation, and switching compared with SEC treatment.

Background Real-world data on long-term treatment patterns associated with interleukin-17A inhibitors in plaque psoriasis are lacking. Objective To compare ixekizumab or secukinumab treatment patterns over a 24-month period among plaque psoriasis patients. Methods Adult patients with psoriasis who had 1 or more claims for ixekizumab or secukinumab between March 1, 2016, and October 31, 2019, and with 24 months of follow-up after starting treatment were identified from IBM MarketScan claims databases. Inverse probability of treatment weighting and multivariable models were employed to balance cohorts and estimate the risks of nonpersistence, discontinuation, and switching and odds of highly adherent treatment (proportion of days covered ≥ 80%). Results A total of 471 ixekizumab and 990 secukinumab users were included. Compared to secukinumab, ixekizumab use was associated with a 20% lower risk of nonpersistence (hazard ratio, 0.80; 95% CI, 0.70-0.92), a 17% lower risk of discontinuation (hazard ratio, 0.83; 95% CI, 0.72-0.96), and a 42% higher odds of being highly adherent to treatment (odds ratio, 1.42; 95% CI, 1.12-1.80). No difference in risk of switching was observed (hazard ratio, 0.83; 95% CI, 0.68-1.01). Limitations Disease severity and clinical outcomes were unavailable. Conclusion Over 24 months, ixekizumab users exhibited better persistence and adherence, and a lower risk of discontinuation than secukinumab users in real-world settings.

Introduction: The impact of cancer care and management beyond treatment is significantly high for cancer patients. Due to the complexities of cancer treatment, patients are heavily reliant upon ancillary support often rendered by friends and family. One significant yet unquantifiable impact of cancer on society is productivity loss of both patients and their caregivers. Non-Hodgkin lymphoma is considered largely incurable with a protracted clinical course punctuated with multiple remission and relapses, warranting repeated treatment and intensive clinical testing, which necessitates significant engagement of patients and caregivers. Many patients are members of the workforce at the age of diagnosis. Both working patients and caregivers need time for medical care, which translates to indirect economic impact due to lost productivity. The objectives of this analysis were to evaluate the productivity loss and indirect costs in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), or Waldenström macroglobulinemia (WM) and their caregivers. Methods: The MarketScan Commercial and Health and Productivity Management databases were used to identify patients with CLL, MCL, MZL, and WM (using ICD-9/ICD-10 codes) who were continuously enrolled for ≥6 months pre- and ≥1 month post-diagnosis (index date) from 1/1/2010 to 12/31/2019. The final study cohort included patients aged 18-64 who were full-time workers with eligibility of absentee, or short-/long-term disability on index date and for ≥1 month in follow-up. Those who were pregnant during the study period were excluded. Adult, full-time employed caregivers, defined as family members covered under the same health plan as the patient, and continuously enrolled ≥6 months pre- and ≥1 month post-index, were also identified. Among those with eligibility, the percentage with a claim of absentee, short- or long-term disability (patients only), and associated productivity time loss and indirect costs during follow-up were examined. Lost wages were calculated using the US Bureau of Labor Statistics 2019 report. For short- or long-term disabilities, mean daily wages were reduced to 70% of typical wages. Productivity time loss and costs were reported per-patient-per-month (PPPM) for each lymphoma. Results: The final patient cohort included 3,450 CLL, 448 MCL, 1,052 MZL and 394 WM patients; the caregiver cohort included 1,435 CLL, 171 MCL, 437 MZL and 190 WM caregivers. Among eligible patients, there were higher proportions of patients that had absentee claims (CLL, 76%; MCL, 72%; MZL, 72%; WM, 82%), followed by short-term disability (CLL, 16%; MCL, 36%; MZL, 18%; WM, 17%) and long-term disability (CLL, 3%; MCL, 10%; MZL, 3%; WM, 3%) (Figure 1A). The proportions of caregivers with absentee claims (CLL, 78%; MCL, 90%; MZL, 69%; WM, 75%) were also higher than those with short-term disability (CLL, 7%; MCL, 10%; MZL, 4%; WM, 8%) (Figure 1B). For all 4 lymphoma types, average illness-related absentee hours were higher in patients than caregivers (CLL, 9.5 vs 6.9; MCL, 44.5 vs 3.6; MZL, 17.0 vs 5.0; WM, 18.2 vs 8.1). A similar pattern was observed for short-term disability days (CLL, 6.9 vs 4.2; MCL, 10.8 vs 3.4; MZL, 7.0 vs 2.2; WM, 6.7 vs 4.8). Average PPPM indirect costs were higher for patients with long-term disability (CLL, $1,433; MCL, $1,233; MZL, $1,302; WM, $2,056) than with short-term disability (CLL, $1,203; MCL, $1,950; MZL, $1,145; WM. $1,177) or absentee claims (CLL, $365; MCL, $1,606; MZL, $612; WM, $662), except for patients with MCL (Figure 2A). Similar trends were observed among caregivers, though the indirect costs due to absenteeism and short-term disability were higher in patients than caregivers (Figure 2B). Conclusions: This real-world evidence study uncovered patients with CLL, MCL, MZL and WM and their caregivers incur substantial disease burden as shown by their productivity loss and indirect costs. Effective treatments that can offer a cure or better remission rates and shorter duration with less toxicity may not only enhance the patients and caregivers' quality of life but also reduce work loss. The availability of oral, targeted therapies has resulted in higher remission rates, durable responses, manageable toxicities and improved quality of life in trials. Future studies are needed to understand the impact of these oral, targeted therapies on patients' and caregivers' productivity. Figure 1 Figure 1. Disclosures Yang: BeiGene, Ltd.: Current Employment. Liu: BeiGene, Ltd.: Current Employment. Irwin: IBM Watson Health: Current Employment; BeiGene, Ltd.: Consultancy. Packnett: IBM Watson Health: Current Employment; BeiGene, Ltd.: Consultancy. Lew: BeiGene, Ltd.: Consultancy; IBM Watson Health: Current Employment. Noxon: BeiGene, Ltd.: Consultancy; IBM Watson Health: Current Employment. Tang: BeiGene, Ltd.: Current Employment. Chanan-Khan: BieGene, Jansen, Ascentage: Consultancy; BeiGene, Jansen, Ascentage: Honoraria; Alpha2 Pharmaceuticals: Patents & Royalties: Tabi; Cellectar: Current equity holder in publicly-traded company; Ascentage, Starton, Cellectar, NonoDev, Alpha2 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Alpha2 Pharmaceuticals, NonoDev, Starton: Current holder of stock options in a privately-held company; Ascentage: Research Funding.

As more biologics become available for the treatment of psoriasis (PsO), there is a lack of direct comparisons of health care costs between patients who are treated by different medications, including ixekizumab (IXE), secukinumab (SEC), and adalimumab (ADA).To compare the real-world health care costs of patients with PsO initiating IXE with those of patients initiating either SEC or ADA.Patients diagnosed with PsO between July 1, 2015, and May 31, 2018, were identified from the IBM MarketScan commercial and Medicare databases. Two weighted patient sample sets were constructed based on drug claims between March 1, 2016, and May 31, 2018: IXE versus SEC and IXE versus ADA. Within each sample, the first claim of eligible drugs was set as the index date. Patients were aged ≥ 18 years and had ≥ 12 months of continuous eligibility before and after the index date. Patients with other indications for the index drug in the preperiod or with use of the index drug within 90 days before the index date were excluded. Inverse probability of treatment weighting (IPTW) was employed to balance cohorts. All-cause and PsO-related health care costs per member per month (PMPM) incurred during the 12-month follow-up period were assessed. Monthly PsO-related pharmacy costs were adjusted using drug discount rates published by the Institute for Clinical and Economic Review (ICER). Annual index drug costs were estimated by adjusting for medication possession ratio and ICER discount rates. All costs were weighted by IPTW.Two study samples were identified: 357 IXE users were compared with 763 SEC users, and 388 IXE users were separately compared with 2,578 ADA users. Before weighting, IXE users were demographically and clinically similar to SEC users but were older and had worse health status than ADA users. Cohorts were balanced postweighting. After weighting, mean monthly all-cause health care costs were $7,313 and $6,477 (After adjusting for drug discount programs (through application of ICER discount rate), this real-world study estimated that average monthly PsO-related costs during the first year of treatment were similar between patients treated with IXE compared with those treated with SEC or ADA.Funding for this study was provided to IBM Watson Health by Eli Lilly and Company. The analysis was conducted independently by IBM Watson Health. Eli Lilly and Company and IBM Watson Health collaborated on study design and interpretation of results. Shi, Lew, and Zimmerman were employed by IBM Watson Health and received funding from Eli Lilly and Company to conduct this study. Zhu, Burge, Malatestinic, Lin, Goldblum, and Murage were employed by Eli Lilly and Company while this study was conducted. Blauvelt has served as a scientific adviser and/or clinical study investigator for AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly and Company, FLX Bio, Galderma, Genentech/Roche, GlaxoSmithKline, Janssen, Leo, Meiji, Merck SharpDohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Revance, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB Pharma, Valeant, and Vidac, and as a paid speaker for AbbVie, Regeneron, and Sanofi Genzyme. A portion of these results were presented at the 2019 International Society for Pharmacoeconomics and Outcomes Research Annual Meeting; May 18-22, 2019; New Orleans, LA, and the 2019 Academy of Managed Care Pharmacy Annual Meeting; March 25-28, 2019; San Diego, CA.

Background:SLE is managed by variable combinations of five drug classes: antimalarials, biologics, corticosteroids, non-steroidal anti-inflammatory agents, and immunosuppressants. Opioids are commonly prescribed to SLE patients despite not being effective for the management of long-term musculoskeletal pain.1Objectives:To describe corticosteroid and opioid use among SLE patients in the United States, and the impact of belimumab initiation on prescribing patterns.Methods:This retrospective study used MarketScan administrative claims databases to select insured adults, age ≥18, with a diagnosis (ICD-9/10 710.0 & M32) of SLE between 1/1/2012 and 5/31/2018 (earliest SLE diagnosis = index date). Patients were followed from index through the earliest of health plan disenrollment or 5/31/2019 (minimum of 12 months). Corticosteroid use was measured in the 12 months following SLE index date. Average daily dose of oral corticosteroids in prednisone equivalents was measured for 12 months after corticosteroid initiation. Opioid use was measured overall, and by strength and length of treatment (chronic use defined as >90 days of supply). Oral corticosteroid and opioid use were compared in the 6 months before and after initiation of belimumab.Results:Of 49,413 SLE patients eligible for analysis, mean [SD] age was 50.1 [14.0] years, 90.2% were female, and average follow-up was 3.6 [1.9] years. 89.8% of patients received any SLE treatment and 68.5% received corticosteroids. The average number of corticosteroid prescriptions was 4.6 [4.1] during 12 months of follow-up. 52.6% of patients had ≥1 claim for an opioid prescription in the 12 months after SLE index and 34.6% were identified as having chronic opioid treatment. Among patients with oral corticosteroid treatment and 12 months of study enrollment post-corticosteroid initiation, the average daily dose for oral corticosteroids was 19.4 [14.2] mg and 59.6% had a high average daily dose of >15mg (Figure 1). Among 1,710 patients with belimumab treatment and 6 months of study enrollment after the first prescription, use of oral corticosteroids decreased by 9.1% (p=0.001), average daily dose decreased from 14.5 [18.4] mg to 11.9 [18.0] mg (pTable 1.Before BelimumabAfter Belimumabp-value, pre vs.(N =1,710)(N =1,710)post BelimumabPatients with an oral steroid prescription (N, %)1,24272.6%1,08663.5%0.001Number of prescriptions (Mean, SD)2.32.32.12.3Average daily dose (Mean, SD)14.518.411.918.0Low average daily dose (>0 to 21012.3%25514.9%0.037Medium average daily dose (7.5 - 38922.7%33419.5%0.041High average daily dose (15 mg or more) (N, %)64337.6%49729.1%Patients with an opioid prescription (N, %)90152.7%86150.4%0.341Weak opioids35620.8%31218.2%0.089Strong opioids69940.9%69540.6%0.915Acute Opioid Use53859.7%48656.4%0.165Chronic opioid use36340.3%37543.6%0.165Conclusion:These results suggest that a strikingly high proportion of patients with SLE are treated with corticosteroids to control the disease and opioid therapy to manage chronic pain. While there was no change in opioid use, corticosteroid use decreased following initiation of belimumab.References:[1]Chen SK, Feldman CH, Brill G, et al. Use of prescription opioids among patients with rheumatic diseases compared to patients with hypertension in the USA: a retrospective cohort study. BMJ 2019;9:e027495Disclosure of Interests: :Julie Birt Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Jianmin Wu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Kirstin Griffing Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Natalia Bello Vega Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Nicole Princic Employee of: I work for IBM Watson Health who was paid by Eli Lilly who funded this research., Isabelle Winer Employee of: I work for IBM Watson Health who was paid by Eli Lilly who funded this research., Carolyn Lew Employee of: I work for IBM Watson Health who was paid by Eli Lilly who funded this research., Karen Costenbader Grant/research support from: Merck, Consultant of: Astra-Zeneca

Introduction Sickle cell disease (SCD) is an inherited disorder in which pathology is driven by hemoglobin polymerization and red blood cell sickling, leading to chronic anemia, hemolysis, and episodic vaso-occlusion. Anemia affects the brain, kidneys and cardiovascular system, and is associated with neurocognitive dysfunction, silent cerebral infarction, stroke, renal dysfunction, pulmonary hypertension, and mortality. Limited research has been conducted to quantify the economic burden of end organ damage among patients with sickle cell disease in the US. Methods Patients with ≥3 nondiagnostic SCD ICD-9/ICD-10 codes within 5 years (Jan 1, 2013-Dec 31, 2017) were identified in the MarketScan® Medicaid claims databases. The first date of SCD diagnosis was the index date. At least three months of continuous enrollment with medical and pharmacy benefits prior to the index date, and at least 1 month of continuous enrollment following the index date were required to be included. Each patient's post-index period was divided into a series of 3-month intervals. For each 3-month interval, patients' entire available claims history (as early as 1/1/2008) was checked to identify four types of end organ damage experienced by SCD patients including stroke (within 1st year and >1 year after an acute stroke event), chronic kidney disease (CKD), end-stage renal disease (ESRD), and pulmonary hypertension (PH). Total healthcare costs (plan paid and patient out-of-pocket payment) and healthcare resource utilization (HRU) information were determined for each 3-month interval. Patient characteristics, HRU, and costs were summarized descriptively by type of end organ damage. Three multivariate generalized linear models with loglink function and gamma error distribution (assuming the cost follows an exponential relationship to the weighted average of covariates) were employed to estimate the relative cost ratios of patients with vs. without end organ damage, controlling for patients' demographic and clinical characteristics. Annualized costs for adult patients with each type of end organ damage were estimated based on the regression results. Results A total of 10,784 patients with SCD on Medicaid were identified. Patients were followed for 3.35 years on average, contributing 152,455 intervals (age ≥18: 42.7%; female: 54.6%; urban: 84.4%). Approximately 20% of the intervals had end organ damage. Patients with end organ damage had more days in hospital, ER visits, outpatient visits, lab tests, and outpatient pharmacy claims per month than patients without organ damage (Figure). The mean (SD) cost per hospitalization for acute stroke was $55,314 ($76, 847). In multivariate regression model 1 (accounting for end organ damage only), patients with any end organ damage had significantly higher costs than those without these conditions. After controlling for patient demographic characteristics (model 2) and additional clinical characteristics (model 3), the results were similar. The costs of SCD patients in the first year after stroke are 4.68 times as high as the costs of patients without any organ damage (2.08 times if >1 yr after stroke; 2.32 times for PH; 2.19 times for CKD; and 3.40 times for ESRD) (Table). The transitional age group (18-30 years) had significantly higher costs than other age groups. Having other SCD complications such as avascular necrosis, gallstones, cholelithiasis, cholecystitis, leg ulcers, osteomyelitis, or priapism also significantly increased the total costs. Based on model 3, after controlling for patient demographics and clinical characteristics, the predicted mean annual costs for adult patients with SCD in the first year after a stroke is $285,816; $127,393 if more than one year after a stroke; $148,174, $135,492, or $209,172 if the patient had PH, CKD or ESRD, respectively. Patients with multiple SCD complications had even higher costs. For example, the predicted mean annual cost for adult patients with CKD and avascular necrosis is $270,513. Conclusions Sickle cell disease is associated with substantial economic burden. When patients experience end organ damage such as stroke, renal dysfunction, or cardiopulmonary conditions, this economic burden is significantly elevated. SCD management strategies that can potentially reduce the risks of end organ damage offer both clinical and economic values to patients and society. Disclosures Song: Global Blood Therapeutics: Other: Xue Song is an employee of IBM Watson Health, which receives funding from Global Blood Therapeutics to conduct research. Campbell:Cyclerion: Consultancy, Research Funding; Novartis: Research Funding; Global Blood Therapeutics: Consultancy, Research Funding. Cong:Global Blood Therapeutics: Employment, Equity Ownership. Agodoa:Global Blood Therapeutics: Employment, Equity Ownership. Martinez:Global Blood Therapeutics: Other: Diane Martinez is an employee of IBM Watson Health, which receives funding from Global Blood Therapeutics to conduct research. Lew:Global Blood Therapeutics: Other: Carolyn Lew is an employee of IBM Watson Health, which receives funding from Global Blood Therapeutics to conduct research. Black:Global Blood Therapeutics: Other: Danae Black is an employee of IBM Watson Health, which receives funding from Global Blood Therapeutics to conduct research. Varker:Global Blood Therapeutics: Other: Helen Varker is an employee of IBM Watson Health, which receives funding from Global Blood Therapeutics to conduct research. Chan:Global Blood Therapeutics: Other: Chris Chan is an employee of IBM Watson Health, which receives funding from Global Blood Therapeutics to conduct research. Lanzkron:Pfizer: Research Funding; Ironwood: Research Funding; Global Blood Therapeutics: Research Funding; HRSA: Research Funding; NIH: Research Funding; PCORI: Research Funding.

The objective of this study was to evaluate all-cause and epilepsy-specific healthcare resource utilization and costs following lacosamide (LCM) initiation as adjunctive therapy for the treatment of epilepsy.A noninterventional retrospective database analysis was conducted that examined patients diagnosed as having epilepsy who added LCM to existing antiepileptic drug (AED) therapy between 2009 and 2016 (the first LCM prescription was the index event). This study used a single-case design whereby patients served as their own controls. Patients were further required to have a minimum of 12 months of continuous eligibility before (preindex period) and after (postindex period) their index event. In the 12-month postindex period, the only allowed AED regimen change was the addition of LCM. Demographic and clinical characteristics were measured at index and during the preindex period, respectively. All-cause and epilepsy-specific healthcare resource utilization and costs were measured and compared in the pre- and postindex periods. Paired t- and McNemar's tests were conducted to assess the significant differences between pre- and postindex. Univariate analyses were used to analyze the impact of LCM on specific subpopulations.The study sample comprised of 2171 patients: mean (standard deviation [SD]) age: 38.9 (19.3) years; 52.6% female. Just over half (56%) of these patients were on monotherapy before adding LCM. Prior to adding LCM, 28.8% of patients had an epilepsy-specific inpatient (IP) admission, and 35.7% of patients had an all-cause IP admission, compared with 18.2% and 26.1% of patients in the post-LCM period, respectively (both p 0.0001). Likewise, 35.6% of patients had an epilepsy-specific emergency room (ER) visit, and 50.0% had an all-cause ER visit prior to adding LCM, compared with 23.8% and 42.1% in post-LCM, respectively (both p 0.0001). After adding LCM, one-year mean [SD] epilepsy-specific IP admission costs decreased by 42.9% ($13,647 [$52,290] to $7788 [$32,321]), and all-cause IP admission costs decreased by 38.6% ($20,654 [$72,716] to $12,688 [$46,120]) (both p 0.0001). One-year epilepsy-specific mean [SD] ER costs decreased by 35.2% ($691 [$1756] to $448 [$1909]; p 0.0001), and all-cause ER cost decreased by 17.8% ($1217 [$3014] to $1000 [$2970]; p 0.01).Epilepsy-related IP hospitalizations and ER visits (indicators of seizures) were significantly reduced in patients with epilepsy 12 months after adding LCM as an adjunctive therapy to existing AED treatment in a real-world setting, leading to reduced healthcare resource utilization and epilepsy costs.