Development and validation of a claims-based algorithm to identify moderate exacerbations in patients with asthma treated in the US.

INTRODUCTION: Definitions of moderate asthma exacerbation have been inconsistent, making their economic burden difficult to assess. An algorithm to accurately identify moderate exacerbations from claims data is needed. METHODS: A retrospective cohort study of Reliant Medical Group patients aged ≥18 years, with ≥1 prescription claim for inhaled corticosteroid/long-acting ß2-agonist, and ≥1 medical claim with a diagnosis code for asthma was conducted. The objective was to refine current algorithms to identify moderate exacerbations in claims data and assess the refined algorithm's performance. Positive and negative predictive values (PPV and NPV) were assessed via chart review of 150 moderate exacerbations events and 50 patients without exacerbations. Sensitivity analyses assessed alternative algorithms and compared healthcare resource utilization (HRU) between algorithm-identified patients (claims group) and those confirmed by chart review (confirmed group) to have experienced a moderate exacerbation. RESULTS: Algorithm-identified moderate exacerbations were: visit of ≤1 day with an asthma exacerbation diagnosis OR visit of ≤1 day with selected asthma diagnoses AND ≥1 respiratory pharmacy claim, excluding systemic corticosteroids, within 14 days after the first claim. The algorithm's PPV was 42%; the NPV was 78%. HRU was similar for both groups. CONCLUSION: This algorithm identified potential moderate exacerbations from claims data; however, the modest PPV underscores its limitations in identifying moderate exacerbations, although performance was partially due to identification of previously unidentified severe exacerbations. Application of this algorithm in future claims-based studies may help quantify the economic burden of moderate and severe exacerbations in asthma when an algorithm identifying severe exacerbations is applied first.

Frequency and economic burden of exacerbations in inhaled corticosteroid/long-acting beta-agonist-treated patients with asthma: A retrospective US claims study.

INTRODUCTION: Despite adherence to inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) therapy, many patients with asthma experience moderate exacerbations. Data on the impact of moderate exacerbations on the healthcare system are limited. This study assessed the frequency and economic burden of moderate exacerbations in patients receiving ICS/LABA. METHODS: Retrospective, longitudinal study analyzed data from Optum's de-identified Clinformatics® Data Mart Database recorded between October 1, 2015, and December 31, 2019. Eligibility criteria included patients ≥18 years of age with ≥1 ICS/LABA claim and ≥1 medical claim for asthma in the 12 months pre-index (first ICS/LABA claim). Primary objectives included describing moderate exacerbation frequency, and associated healthcare resource utilization (HRU) and costs. A secondary objective was assessing the relationship between moderate exacerbations and subsequent risk of severe exacerbations. Patients were stratified by moderate exacerbation frequency in the 12 months post index. Moderate exacerbations were identified using a newly developed algorithm. RESULTS: In the first 12 months post index 61.6% of patients experienced ≥1 moderate exacerbation. Mean number of asthma-related visits was 4.1 per person/year and median total asthma-related costs was $3544. HRU and costs increased with increasing exacerbation frequency. Outpatient and inpatient visits accounted for a similar proportion of these costs. Moderate exacerbations were associated with an increased rate and risk of future severe exacerbations (incidence rate ratio, 1.56; hazard ratio, 1.51 [both p < 0.001]). CONCLUSIONS: This study highlighted that a high proportion of patients continue to experience moderate exacerbations despite ICS/LABA therapy and subsequently experience increased economic burden and risk of future severe exacerbations.

Progression-Free Survival of Daratumumab Versus Bortezomib Triplet Combination With Lenalidomide and Dexamethasone in Transplant Ineligible Patients With Newly Diagnosed Multiple Myeloma: TAURUS Chart Review Study.

BACKGROUND: Daratumumab, lenalidomide and dexamethasone (DRd) and bortezomib, lenalidomide and dexamethasone (VRd) are preferred regimens for transplant ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). Both DRd and VRd demonstrated superior efficacy versus Rd in the MAIA and SWOG S0777 trials, respectively, but there is no head-to-head (H2H) clinical trial comparing their efficacy. Differing populations in the MAIA and S0777 trials make an unadjusted comparison of outcomes challenging and biased. The current TAURUS study is the first real-world H2H study comparing progression-free survival (PFS) among TIE NDMM patients treated with DRd or VRd as first-line (1L) in similar clinical settings. MATERIALS AND METHODS: A multicenter chart review study was conducted at nine sites across the United States. All TIE patients treated with DRd and a randomly selected population of VRd patients were included. TIE NDMM patients aged ≥65 were included if they initiated 1L DRd/VRd between January 2019 and September 2021. PFS was defined as the time from DRd/VRd initiation until disease progression or death. A doubly-robust multivariable Cox regression model combined with inverse probability of treatment weighting (IPTW) methodology was used to compare PFS between cohorts. RESULTS: Weighted cohorts comprised 91 DRd and 87 VRd patients. Thirteen DRd and 24 VRd patients experienced progression/death. Patients treated with DRd had a lower risk of progression/death versus VRd (adjusted hazard ratio: 0.35, 95% confidence interval: [0.17; 0.73]). CONCLUSION: DRd is associated with a significantly lower risk of disease progression or death compared to VRd as 1L treatment for TIE NDMM patients.

Burden of Herpes Zoster Among Patients with Psoriasis in the United States.

INTRODUCTION: Patients with psoriasis (PsO) are at increased risk of herpes zoster (HZ), but recent data on the incidence of HZ among patients with PsO and the impact of HZ on healthcare resource use (HRU) and costs for patients with PsO have not been described. METHODS: This retrospective, longitudinal, cohort study estimated HZ incidence in cohorts of adults with vs without PsO (PsO + vs PsO-) and HRU and costs among those with PsO, with vs without HZ (PsO + /HZ + vs PsO + /HZ-) using Optum's de-identified Clinformatics Data Mart Database during 2015-2020. Patients with psoriatic arthritis were excluded from all four cohorts. Comparisons between cohorts used generalized linear models to adjust outcomes based on various baseline characteristics. RESULTS: The incidence rate of HZ was significantly higher in the PsO + (n = 144,115) vs PsO- (n = 23,837,237) cohorts at 11.35 vs 7.67 per 1000 patient-years; adjusted incidence rate ratio (aIRR): 1.21, 95% confidence interval (CI): 1.16-1.25. HRU (outpatient, emergency department, and inpatient) was significantly higher in the PsO + /HZ + (n = 1859) vs PsO + /HZ- (n = 78,664) cohorts during 1 month and 3 months after HZ diagnosis (e.g., outpatient visits during month: 2.83 vs 1.30 per patient; aIRR: 1.96; 95% CI 1.86-2.06). Mean all-cause costs were also significantly higher in the PsO + /HZ + vs PsO + /HZ- cohort during both month ($5020 vs $2715 per patient; adjusted cost difference: $1390; 95% CI $842-$1964) and 3 months ($12,305 vs $8256; adjusted cost difference: $1422; 95% CI $280-$2889) after HZ diagnosis. CONCLUSION: These findings show the increased incidence of HZ among patients with PsO and the clinical and economic burdens of HZ in this population. Considering the high prevalence of PsO, insights into the impact of HZ in these patients provide valuable evidence to inform clinical decision-making.

Psoriasis is an inflammatory condition that causes flaky, scaly skin. Herpes zoster (shingles) causes a painful rash, usually on the abdomen. However, recent data on the proportion of patients with psoriasis who develop herpes zoster is lacking. Furthermore, little is known about the healthcare resources that are used or the costs of care for patients with psoriasis who develop herpes zoster. We found that patients with psoriasis were 21% more likely to have herpes zoster than patients without psoriasis. Among patients with psoriasis, those who developed herpes zoster had twice as many doctor's visits, 3 times as many emergency department visits, and twice as many inpatient hospital stays during the month after a herpes zoster diagnosis as patients without herpes zoster. This resulted in an additional cost of $1390 per patient with psoriasis and herpes zoster compared with those with psoriasis but without herpes zoster. Overall, patients with psoriasis are at increased risk of developing herpes zoster and the healthcare resource use and associated cost of treating herpes zoster in patients with psoriasis is substantial.

Economic and Clinical Burden of Herpes Zoster Among Patients With Inflammatory Bowel Disease in the United States.

Background: Patients with ulcerative colitis (UC) or Crohn's disease (CD) are at increased risk of herpes zoster (HZ); however, relevant cost and healthcare resource utilization (HCRU) data are limited. Methods: We estimated HCRU (hospitalization, emergency department [ED], and outpatient visits) and costs in patients with UC or CD, with and without HZ, using administrative claims data (October 2015-February 2020). HCRU and costs (2020 US dollars) were compared at 1 month, 1 quarter, and 1 year after the index date, using propensity score adjustment and generalized linear models. Results: In total, 20 948 patients were included: UC+/HZ+ (n = 431), UC+/HZ- (n = 10 285), CD+/HZ+ (n = 435), and CD+/HZ- (n = 9797). Patients with HZ had higher all-cause HCRU rates and all-cause total healthcare costs relative to those without HZ. In the first month, adjusted incidence rate ratios (aIRRs) for hospitalizations and ED visits for patients with UC and HZ compared with UC alone were 2.87 (95% confidence interval [CI], 1.93-4.27) and 2.66 (95% CI,1.74-4.05), respectively; for those with CD and HZ, aIRRs were 3.34 (95% CI, 2.38-4.70) and 3.31 (95% CI, 2.32-4.71), respectively, compared with CD alone (all P < .001). Adjusted cost differences in UC and CD cohorts with HZ over the first month were $2189 and $3774, respectively, chiefly driven by higher inpatient costs. The incremental impact on HCRU and costs in cohorts with HZ predominantly occurred during the first quarter following diagnosis. Conclusions: HZ is associated with increased HCRU and costs in patients with UC and CD, especially shortly after diagnosis.

Clinical and Economic Burden of Herpes Zoster in Patients with Rheumatoid Arthritis: A Retrospective Cohort Study Using Administrative Claims.

OBJECTIVE: To estimate the incremental healthcare resource utilization (HRU) and cost burden posed by herpes zoster (HZ) in adult patients with rheumatoid arthritis (RA) in the United States. METHODS: A retrospective cohort study was conducted using an administrative claims database containing commercial and Medicare Advantage with Part D data, between October 2015 and February 2020. Patients with RA and HZ (RA+/HZ+) or RA without HZ (RA+/HZ-) were identified based on diagnosis codes and relevant medications. Outcomes measured included HRU and medical, pharmacy, and total costs at month 1, quarter 1, and year 1 after the index date (HZ diagnosis for RA+/HZ+ cohort, randomly assigned for RA+/HZ- cohort). Generalized linear models incorporating propensity scores and other covariates were used to estimate differences in outcomes between cohorts. RESULTS: A total of 1866 patients from the RA+/HZ+ cohort and 38,846 patients from the RA+/HZ- cohort were included. Hospitalizations and emergency department visits occurred more frequently in the RA+/HZ+ than the RA+/HZ- cohort, especially in the month after HZ diagnosis (adjusted incidence rate ratio [95% confidence interval (CI)] for hospitalizations: 3.4 [2.8; 4.2]; emergency department visits: 3.7 [3.0; 4.4]). Total costs were also higher in the month after HZ diagnosis (mean adjusted cost difference [95% CI]: $3404 [$2089; $4779]), with cost differences driven by increased medical costs ($2677 [$1692; $3670]). CONCLUSIONS: These findings highlight the high economic burden of HZ among individuals with RA in the United States. Strategies to reduce the risk of HZ in patients with RA (such as vaccination) may serve to reduce this burden. Video abstract.

Incidence and risk of herpes zoster in patients with ulcerative colitis and Crohn's disease in the USA.

Background: Patients with inflammatory bowel disease (IBD) are at increased risk of herpes zoster (HZ). We evaluated the incidence of HZ in ulcerative colitis (UC) and Crohn's disease (CD) patients and compared this with HZ incidence in a non-IBD population. Methods: We conducted a retrospective cohort study (GSK study identifier: VEO-000043) of adults aged ≥18 years with UC and CD and without IBD who were identified from claims recorded in a US healthcare database between October 2015 and February 2020. Crude HZ incidence rates/1,000 person-years (PY) were calculated, and comparisons of HZ incidence rates between UC or CD and non-IBD cohorts were made using adjusted generalized linear models. Results: The study population comprised a total of 29,928 UC, 25,959 CD, and 11,839,329 non-IBD patients. Crude overall HZ incidence rates were 13.64/1,000 PY (UC), 15.94/1,000 PY (CD), and 7.95/1,000 PY (non-IBD). UC and CD patients had increased HZ incidence rates, with adjusted incidence rate ratios of 1.35 (95% confidence interval [CI], 1.26-1.44) and 1.66 (95% CI, 1.56-1.77), respectively, compared with non-IBD patients. Stratified analysis indicated increased relative rates of HZ in progressively younger age strata in the UC and CD patients compared with non-IBD patients. HZ incidence rates were higher in UC and CD patients who had previously received thiopurines or methotrexate, TNF-inhibitors, or corticosteroids than in UC and CD patients who did not take those medicines. Conclusion: UC and CD patients had increased HZ incidence rates compared with patients without IBD, demonstrating the importance of HZ prevention in IBD patients.

Incidence of Herpes Zoster in Patients With Rheumatoid Arthritis in the United States: A Retrospective Cohort Study.

OBJECTIVE: To estimate the incidence of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) compared with the general population in the USA. METHODS: This retrospective, longitudinal cohort study used data from an administrative claims database containing both commercial and Medicare Advantage Part D data, with a data period from October 2015 to February 2020. Patients were aged ≥ 18 years and divided into 2 cohorts: patients with RA and patients without RA. Diagnosis and procedure codes were used to identify HZ cases and calculate incidence rates (IRs) of HZ in the 2 cohorts. Data were stratified by age group (ie, 18-49, 18-29, 30-39, 40-49, 50-64, and ≥ 65 yrs) and RA therapy type. IR ratios (IRRs), adjusted by cohort baseline characteristics, were estimated using generalized linear models to compare the incidence of HZ between cohorts. RESULTS: The overall IR of HZ was higher in the RA cohort (21.5 per 1000 person-years [PY]; N = 67,650) than in the non-RA cohort (7.6 per 1000 PY; N = 11,401,743). The highest IRs in both cohorts were observed in the age group of ≥ 65 yrs (23.4 and 11.4 per 1000 PY in the RA cohort and non-RA cohort, respectively). The overall adjusted IRR of HZ was 1.93 (95% CI 1.87-1.99, P < 0.001) for the RA cohort compared with the non-RA cohort. In the RA cohort, the highest IRs by medication class were observed in patients using corticosteroids and those using Janus kinase inhibitors. CONCLUSION: These results highlight the increased incidence of HZ in patients with RA.

Chronic obstructive pulmonary disease is associated with an increased risk of herpes zoster: A retrospective United States claims database analysis.

Chronic obstructive pulmonary disease (COPD) has been reported as a potential risk factor for developing herpes zoster (HZ). We aimed at comparing incidence rates of HZ between people with versus without COPD in the US. This retrospective cohort study used data from Optum's de-identified Clinformatics Data Mart database from 1/1/2013 through 12/31/2018. We identified two cohorts of people ≥40 years without prior HZ, HZ vaccination, postherpetic neuralgia (PHN) or HZ ophthalmicus: those with (COPD+) and those without (COPD-) a COPD diagnosis. Adjusted incidence rate ratios (aIRRs) of HZ and PHN were calculated using generalized linear models, controlling for the propensity score of being diagnosed with COPD and relevant demographic and clinical characteristics. People in the COPD+ cohort (n = 161 970) were considerably older, had more comorbidities and were more likely to use corticosteroids than those in the COPD- cohort (n = 9 643 522). The incidence rate of HZ was 5.7-fold higher in the COPD+ versus COPD- cohorts (13.0 vs. 2.3 per 1000 person-years [PY]; aIRR, 2.77; 95% confidence interval [CI], 2.69 to 2.85; P < 0.001). The unadjusted incidence rate of PHN was 1.7-fold higher in the COPD+/HZ+ versus COPD-/HZ+ cohort (64.8 vs. 37.1 per 1000 PY), but not after adjustment (aIRR, 1.07; 95% CI, 0.79 to 1.45). HZ and PHN incidence rates increased with age. After adjustment, COPD+ adults had a 2.8-fold increased risk of developing HZ. These results may help to increase awareness about potential risk factors for HZ and highlight the need for vaccination among those at increased risk.

Long-Term Effectiveness and Safety of Dutasteride versus Finasteride in Patients with Male Androgenic Alopecia in South Korea: A Multicentre Chart Review Study.

BACKGROUND: Dutasteride improves hair growth compared with finasteride in male androgenic alopecia (AGA) and is well tolerated. However, real-world evidence for long-term dutasteride use in AGA is lacking. OBJECTIVE: To describe baseline characteristics, treatment patterns and long-term safety and effectiveness of dutasteride versus finasteride. METHODS: This was a multicentre, retrospective medical chart review study conducted in South Korea. The index date was the first prescription of dutasteride or finasteride. Baseline characteristics were assessed 6 months prior to index. Safety and effectiveness (improvements in basic and specific [BASP] classification) data were collected from index throughout the observation period. RESULTS: Overall, 600 male adult patients were included (dutasteride, n=295; finasteride, n=305). Dutasteride-treated patients were older (p<0.001) and more likely to have moderate/severe BASP classification at baseline (p=0.010) compared with finasteride-treated patients. Among patients treated with recommended, on-label dosing exclusively (n=535: dutasteride, n=250; finasteride, n=285), dutasteride-treated patients showed greater improvement in hair growth than finasteride-treated patients, as measured by the BASP basic M classification (adjusted incidence rate ratio [95% confidence interval]: 2.06 [1.08, 3.95]; p=0.029). Among this same subset, overall occurrence of adverse events (AEs) during the observation period were not statistically equivalent between groups (dutasteride 7.6%, finasteride 10.5%; p=0.201), although reports of AEs of special interest were equivalent (p<0.001). CONCLUSION: Dutasteride showed greater effectiveness than finasteride in improving BASP classification in treating male AGA and had a similar or possibly lower occurrence of overall AEs. Dutasteride may provide an effective and safe treatment option for male patients with AGA.

Assessment of the Impact of a Meningitis/Encephalitis Panel on Hospital Length of Stay: A Systematic Review and Meta-Analysis.

Meningitis and encephalitis are central nervous system infections with considerable morbidity and mortality. The BioFire® FilmArray® Meningitis/Encephalitis Panel (multiplex ME panel) can identify pathogens rapidly potentially aiding in targeted therapy and curtail antimicrobial exposure. This systematic review and meta-analysis synthesized the literature on the association between the multiplex ME panel and length of hospital stay (LOS), length of acyclovir therapy, and days with antibiotics. MEDLINE and EMBASE were searched. Only studies presenting novel data were retained. Random-effects meta-analyses were performed to assess the impact of the multiplex ME panel on outcomes. Of 169 retrieved publications, 13 met the criteria for inclusion. Patients tested with the multiplex ME panel had a reduction in the average LOS (mean difference [MD] [95% CI]: -1.20 days [-1.96, -0.44], n = 11 studies). Use of the multiplex ME panel was also associated with a reduction in the length of acyclovir therapy (MD [95% CI]: -1.14 days [-1.78, -0.50], n = 7 studies) and a nonsignificant reduction in the average number of days with antibiotics (MD [95% CI]: -1.01 days [-2.39, 0.37], n = 6 studies). The rapidity of pathogen identification contributes to an overall reduced LOS, reductions in the duration of empiric antiviral utilization, and a nonsignificant reduction in antibiotic therapy.

Patient characteristics, treatment patterns, and outcomes among black and white patients with multiple myeloma initiating daratumumab: A real-world chart review study.

BACKGROUND: Daratumumab was approved for multiple myeloma (MM) in 2015. While its safety and efficacy are well documented, there is limited real-world information on its use and outcomes in patients of different races. METHODS: We conducted a retrospective chart review of adult patients with MM initiating daratumumab in any line of therapy (LOT) between November 2015 and May 2020. De-identified data were retrieved from 2 US clinical sites; patient characteristics, treatment patterns, and response rate were described for black and white patients, stratified by LOT. Overall response rate (ORR), progression-free survival (PFS), and time to next LOT (TTNT) were compared between black and white patients initiating daratumumab in second line (2L) or later, adjusting for age and number of prior lines. RESULTS: Two hundred and fifty-two patient charts (89 black, 163 white) were extracted. Black patients were younger at diagnosis (61.7 vs. 67.0 years) and had a similar proportion of females (black: 44.9%, white: 46.6%). Black patients had longer time between MM diagnosis and daratumumab initiation (43.2 vs. 34.1 months) and received more prior LOTs (median 3.0 vs. 2.0). ORR for black and white patients initiating daratumumab in 1L was 100.0%, with very good partial response or better in 75.0% and 66.7%, respectively. Similar trends were observed in 2L and 3L+. There were no significant differences in ORR, PFS, or TTNT between groups. CONCLUSION: Daratumumab had similar clinical outcomes (ORR, PFS, and TTNT) in black and white patients. Black patients initiated daratumumab later in their treatment, suggesting potential discrepancies in access to new MM treatments.

Evaluation of treatment patterns, healthcare resource utilization, and costs among patients receiving treatment for cytomegalovirus following allogeneic hematopoietic cell or solid organ transplantation.

AIM: Management of cytomegalovirus (CMV) infection/disease in transplant recipients may be complicated by toxicities and resistance to conventional antivirals, adding to the overall healthcare burden. We characterized treatment patterns, healthcare resource utilization (HCRU), and costs to elucidate the healthcare burden associated with CMV therapies post-transplant. MATERIALS AND METHODS: A retrospective, longitudinal cohort study of transplant recipients using data from a US commercial insurance claims database (2013-2017) was conducted. Patients with a claim for post-transplant CMV diagnosis and anti-CMV treatment (ganciclovir, valganciclovir, foscarnet, or cidofovir) were identified (Treated CMV cohort) and compared with patients with neither a claim for CMV diagnosis nor anti-CMV treatment (No CMV cohort) for outcomes including HCRU and associated costs. Allogeneic hematopoietic cell transplantation (HCT) or solid organ transplantation (SOT) recipients were analyzed separately. Anti-CMV treatment patterns were assessed in the Treated CMV cohort. Costs were evaluated among subgroups with myelosuppression or nephrotoxicity. RESULTS: Overall, 412 allogeneic HCT and 899 SOT patients were included in the Treated CMV cohorts, of which 41.7% and 52.5%, respectively, received multiple antiviral courses. Treated CMV cohorts compared with No CMV cohorts had higher mean monthly healthcare visits per patient (allogeneic HCT: 8.83 vs 6.61, SOT: 5.61 vs 4.45) and had an incremental adjusted mean monthly cost per patient differences of $8,157 (allogeneic HCT, p < .004) and $2,182 (SOT, p < .004). Among Treated CMV cohorts, HCRU and costs increased with additional CMV antiviral treatment courses. Mean monthly costs were higher for patients with than without myelosuppression or nephrotoxicity. LIMITATIONS: Results may not be generalizable to patients covered by government insurance or outside the USA. CONCLUSIONS: CMV post-transplant managed with conventional treatment is associated with substantial HCRU and costs. The burden remains particularly high for patients requiring multiple treatment courses for post-transplant CMV or for transplant recipients who develop myelosuppression or nephrotoxicity.

Treatment patterns and effectiveness of patients with multiple myeloma initiating Daratumumab across different lines of therapy: a real-world chart review study.

BACKGROUND: Daratumumab, a CD38 monoclonal antibody, has demonstrated efficacy as monotherapy and combination therapy across several indications, both among newly-diagnosed and refractory patients with multiple myeloma (MM). However, there is limited evidence on treatment patterns and effectiveness of daratumumab in the real-world setting, particularly in first line (1 L). This study aimed to describe real-world treatment patterns and clinical outcomes among patients initiating daratumumab across different lines of therapy. METHODS: A retrospective chart review of adult patients with MM initiating daratumumab between November 2015 and March 2021 was conducted at two clinical sites in the United States. De-identified patient-level data were abstracted in an electronic case report form. Patient characteristics and treatment patterns were described. Clinical outcomes including overall response rate (ORR), progression-free survival, and time to next line of therapy were reported using descriptive statistics and stratified by line of therapy (1 L, second line [2 L] or third line or later [3 L+]). A sub-group analysis evaluated treatment patterns and ORR among patients re-treated with daratumumab. RESULTS: A total of 299 patients were included in the study (mean age: 68 years; 55% male). Among them, 26 were 1 L patients, 66 were 2 L patients, and 207 were 3 L+ patients; 110 patients (36.8%) received a stem cell transplant prior to daratumumab initiation. The mean duration of follow-up was 10 months among 1 L patients and 19 months among 2 L and 3 L+ patients. Patients who initiated daratumumab in 1 L had a 100% ORR, while those initiating in 2 L and 3 L+ had an ORR of 78.8 and 65.2%, respectively. Among re-treated patients, ORR was 66.7% during the first treatment segment, and 52.9% during the second treatment segment. Kaplan-Meier rates of progression-free survival at 12 months were 89.9, 75.2, and 53.1% among patients who initiated daratumumab in 1 L, 2 L, and 3 L+, respectively. Kaplan-Meier rates of time to next line of therapy at 12 months were 94.1, 73.4, and 50.0% among patients who initiated daratumumab in 1 L, 2 L, and 3 L+, respectively. CONCLUSIONS: These findings suggest that daratumumab-based regimens are an effective treatment option across all lines of therapy, with highest response rate in 1 L.

Increased Health Care Resource Utilization and Costs Associated with Herpes Zoster Among Patients Aged ≥50 Years with Chronic Obstructive Pulmonary Disease in the United States.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are potentially at increased risk of herpes zoster (HZ). Little is known about the impact of an HZ episode on health care resource utilization (HRU) and costs among patients with COPD. METHODS: This retrospective cohort study of individuals aged ≥50 years in the United States (US) used administrative claims data from Optum's de-identified Clinformatics Data Mart Database for commercially insured and Medicare Advantage members (2013-2018). Two cohorts of patients with COPD, with HZ (COPD+/HZ+) and without HZ (COPD+/HZ-), were identified. All-cause and COPD-related HRU rates and costs (2018 US dollars) were compared between cohorts for up to 12 months of follow-up. Comparisons were controlled for baseline differences through propensity score adjustment. RESULTS: A total of 3415 COPD+/HZ+ and 35,360 COPD+/HZ- patients (mean ages 73.2 ± 9.0 and 72.4 ± 9.4 years, respectively) were identified. Patients in the COPD+/HZ+ versus COPD+/HZ- cohort had increased use of all-cause (adjusted incidence rate ratio [aIRR] 1.17; 95% confidence interval [CI] 1.14, 1.21) and COPD-related (aIRR 1.27; 95% CI 1.21, 1.34) medical services (both P<0.001) and higher mean total all-cause ($4140 versus $3749 per person per month [PPPM]; adjusted cost difference +$313 PPPM) and COPD-related ($1541 versus $1231 PPPM; +$152 PPPM) costs (both P<0.004) in the year after HZ. CONCLUSIONS: HRU and cost burden is higher in patients with COPD with vs without HZ. These results could help to estimate the potential cost benefits of HZ vaccination among patients with COPD.

Development and Validation of a Healthcare Utilization-Based Algorithm to Identify Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Introduction: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are important events that may precipitate other adverse outcomes. Accurate AECOPD event identification in electronic administrative data is essential for improving population health surveillance and practice management. Objective: Develop codified algorithms to identify moderate and severe AECOPD in two US healthcare systems using administrative data and electronic medical records, and validate their performance by calculating positive predictive value (PPV) and negative predictive value (NPV). Methods: Data from two large regional integrated health systems were used. Eligible patients were identified using International Classification of Diseases (Ninth Edition) COPD diagnosis codes. Two algorithms were developed: one to identify potential moderate AECOPD by selecting outpatient/emergency visits associated with AECOPD-related codes and antibiotic/systemic steroid prescriptions; the other to identify potential severe AECOPD by selecting inpatient visits associated with corresponding codes. Algorithms were validated via patient chart review, adjudicated by a pulmonologist. To estimate PPV, 300 potential moderate AECOPD and 250 potential severe AECOPD events underwent review. To estimate NPV, 200 patients without any AECOPD identified by the algorithms (100 patients each without moderate or severe AECOPD) during the two years following the index date underwent review to identify AECOPD missed by the algorithm (false negatives). Results: The PPVs (95% confidence interval [CI]) for both moderate and severe AECOPD were high: 293/298 (98.3% [96.1-99.5]) and 216/225 (96.0% [92.5-98.2]), respectively. NPV was lower for moderate AECOPD (75.0% [65.3-83.1]) than for severe AECOPD (95.0% [88.7-98.4]). Results were consistent across both healthcare systems. Conclusion: This study developed healthcare utilization-based algorithms to identify moderate and severe AECOPD in two separate healthcare systems. PPV for both algorithms was high; NPV was lower for the moderate algorithm. Replication and consistency of results across two healthcare systems support the external validity of these findings.

Real-World Evidence of the Clinical and Economic Impact of Long-Acting Injectable Versus Oral Antipsychotics Among Patients with Schizophrenia in the United States: A Systematic Review and Meta-Analysis.

BACKGROUND: Long-acting injectable (LAI) antipsychotics, compared with oral antipsychotics (OA), have been found to significantly improve patient outcomes, including reduced hospitalizations and emergency room (ER) admissions and increased medication adherence among adult patients with schizophrenia. In turn, the clinical benefits achieved may translate into lower economic burden. Real-world evidence of the comparative effectiveness of LAI is needed to understand the potential benefits of LAI outside of the context of clinical trials. This study aimed to provide a comprehensive synthesis of recent published real-world studies comparing healthcare utilization, costs, and adherence between patients with schizophrenia treated with LAI versus OA in the United States. METHODS: In this systematic literature review, MEDLINE® was searched for peer-reviewed, real-world studies (i.e., retrospective or pragmatic designs) published in English between January 1, 2010 and February 10, 2020. Comparative studies reporting hospitalizations, ER admissions, healthcare costs, or medication adherence (measured by proportion of days covered [PDC]) in adults with schizophrenia treated with LAI versus OA (or pre- vs post-LAI initiation) in the United States were retained. Random effects meta-analyses were conducted among eligible studies to evaluate the association of LAI versus OA use on hospitalizations, ER admissions, healthcare costs, and treatment adherence. A sensitivity analysis among the subset of studies that compared OA with paliperidone palmitate once monthly (PP1M), specifically, was conducted. RESULTS: A total of 1083 articles were identified by the electronic literature search, and two publications were manually added subsequently. Among the 57 publications meeting the inclusion criteria, 25 provided sufficient information for inclusion in the meta-analyses. Compared with patients treated with OA, patients initiated on LAI had lower odds of hospitalization (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.54-0.71, n = 7), fewer hospitalizations (incidence rate ratio [IRR] [95% CI] 0.75 [0.65-0.88], n = 9), and fewer ER admissions (IRR [95% CI] 0.86 [0.77-0.97], n = 6). The initiation of LAI was associated with higher per-patient-per-year (PPPY) pharmacy costs (mean difference [MD] [95% CI] $5603 [3799-7407], n = 6), which was offset by lower PPPY medical costs (MD [95% CI] - $5404 [- 7745 to - 3064], n = 6), resulting in no significant net difference in PPPY total all-cause healthcare costs between patients treated with LAI and those treated with OA (MD [95% CI] $327 [- 1565 to 2219], n = 7). Patients initiated on LAI also had higher odds of being adherent to their medication (PDC ≥ 80%; OR [95% CI] 1.89 [1.52-2.35], n = 9). A sensitivity analysis on a subset of publications evaluating PP1M found results similar to those of the main analysis conducted at the LAI class level. CONCLUSIONS: Based on multiple studies with varying sub-types of patient populations with schizophrenia in the United States published in the last decade, this meta-analysis demonstrated that LAI antipsychotics were associated with improved medication adherence and significant clinical benefit such as reduced hospitalizations and ER admissions compared with OA. The lower medical costs offset the higher pharmacy costs, resulting in a non-significant difference in total healthcare costs. Taken together, these findings provide strong evidence on the clinical and economic benefits of LAI compared with OA for the treatment of schizophrenia in the real world.