Real-world Dosing Patterns Research Articles

Real-world dosing patterns of regorafenib for patients with metastatic colorectal cancer in Spain: the RE-SEARCH study.

To describe the dosing patterns of regorafenib in a real-world population of patients with metastatic colorectal cancer (mCRC) in a routine clinical practice setting in Spain, focusing on the starting dose of regorafenib. An observational, retrospective, multicenter study that included patients ≥ 18years old who had histologically documented mCRC and who had initiated treatment with regorafenib since January 2017. Post hoc categorization of dosing patterns revealed the following: initial dose < 160mg and dose escalation, initial dose < 160mg and maintenance, initial dose equal to 160mg and maintenance, and initial dose equal to 160mg and dose reduction. Most patients (152/241, 63.8%) initiated treatment with regorafenib at doses < 160mg. There was large variation in the starting dose of regorafenib over time: in 2017, most patients (59%) initiated regorafenib at a dose of 160mg, this proportion decreased to 6% in 2021. There were no significant differences in the median progression-free survival according to the regorafenib dose patterns during the first two cycles. The proportion of patients who reported at least one adverse event (AE), had a grade 3-4 AE or had an AE leading to dose reduction was greater in the group of patients who received an initial dose equal to 160 and reduction. Our results indicate that physicians in Spain have gradually adopted a dose-escalation approach during cycle 1, which is a common practice for starting treatment with a reduced dose (< 160mg/day), a strategy that seems to improve tolerability while maintaining efficacy. Not applicable.

Analysis of real-world (RW) pomalidomide (pom) dosing patterns in patients (pts) with multiple myeloma (MM) from the Flatiron database.

e19508 Background: Pom is an immunomodulatory drug commonly used in combination with other antimyeloma therapies for the treatment (tx) of pts with MM. However, there is a paucity of data on RW dosing patterns with pom and associated tx outcomes. We report RW pom dosing patterns and effectiveness using RW data to inform potential pom dosing strategies as part of combination tx regimens. Methods: RW pom data in pts with MM were derived from the US Flatiron Health deidentified electronic health record (EHR) database (Jan 2011–Nov 2021). Pom starting dose (1, 2, 3, or 4 mg) and line of therapy (LOT) were identified from EHRs. Tx patterns were captured per LOT; pts could receive &gt;1 pom-containing tx regimen/LOT. Pts receiving pom were followed until Dec 2023 for outcome analysis. Overall survival (OS) and time to next tx (TTNT) were estimated using the Kaplan-Meier method and analyzed by log-rank testing. Results: Of 15,378 pts with MM, 2,034 had an order for pom, of whom 1,344 received pom and 880 had LOT data. The most common initial pom dose was 4 mg (50%), followed by 2 mg (30%), 3 mg (16%), and 1 mg (4%). The most common pom-containing tx regimens were: daratumumab + pom + dexamethasone (d; 29%), pom + d (18%), and carfilzomib + pom + d (14%); 6% of pts received pom monotherapy. Retreatment with pom was infrequent, with 84% of pts receiving only 1 pom-containing LOT. Most pts (n=652, 74%) remained on the initial pom dose received; of these, 367 pts remained on an initial dose of 4 mg. Among pts who changed dose (n=227, 26%), 36% changed from 2 mg and 36% changed from 4 mg. Of pts who received an initial dose of 4 mg and changed dose (n=81), 43%, 51%, and 6% reduced to 3, 2, and 1 mg, respectively. Of pts who received an initial dose of 2 mg and changed dose (n=82), 17% reduced to 1 mg. Among pts who received an initial dose of &lt;4 mg and changed dose, dose escalation was common (67% of pts with a 3 mg initial dose increased to 4 mg; 33% and 50% of pts with a 2 mg initial dose increased to 3 and 4 mg, respectively). Outcome analysis of pts with LOT and available follow-up data suggest that initial pom dose had no impact on OS and TTNT (Table). Log-rank analysis of OS and TTNT between the initial doses of 2 and 4 mg showed no significant difference among all pts ( P=0.32) or in pts who changed dose ( P=0.29). Conclusions: RW analyses show that most pts remain on the initial pom dose received, but some pts changed doses. Pom, most commonly used in combination regimens, can be used across an initial dose range with no impact on efficacy in pts with MM. Optimal pom dosing may vary across pts and combination regimens; pom dosing should be tailored to pt needs per disease and tx factors. [Table: see text]

CLL-586 Real-World Dosing Patterns and Outcomes Among Patients With Chronic Lymphocytic Leukemia With or Without Dose Adjustment of First-Line Ibrutinib

CLL-586 Real-World Dosing Patterns and Outcomes Among Patients With Chronic Lymphocytic Leukemia With or Without Dose Adjustment of First-Line Ibrutinib

POSTER: CLL-403 Real-World Dosing Patterns and Time to Next Treatment for Previously Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With or Without Ibrutinib Dose Reduction Following an Adverse Event

POSTER: CLL-403 Real-World Dosing Patterns and Time to Next Treatment for Previously Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With or Without Ibrutinib Dose Reduction Following an Adverse Event

POSTER: CLL-586 Real-World Dosing Patterns and Outcomes Among Patients With Chronic Lymphocytic Leukemia With or Without Dose Adjustment of First-Line Ibrutinib

POSTER: CLL-586 Real-World Dosing Patterns and Outcomes Among Patients With Chronic Lymphocytic Leukemia With or Without Dose Adjustment of First-Line Ibrutinib

CLL-403 Real-World Dosing Patterns and Time to Next Treatment for Previously Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With or Without Ibrutinib Dose Reduction Following an Adverse Event

CLL-403 Real-World Dosing Patterns and Time to Next Treatment for Previously Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With or Without Ibrutinib Dose Reduction Following an Adverse Event

P-3 Real-world dosing patterns of regorafenib in patients with metastatic colorectal cancer in Spain: The RE-SEARCH study

P-3 Real-world dosing patterns of regorafenib in patients with metastatic colorectal cancer in Spain: The RE-SEARCH study

HSR23-105: Real-World Dosing Patterns in Patients With Anaplastic Lymphoma Kinase Positive (ALK+) Non–Small Cell Lung Cancer (NSCLC) Treated With Brigatinib in the Front-Line (FL) Setting in the United States: A Claims Database Analysis

"HSR23-105: Real-World Dosing Patterns in Patients With Anaplastic Lymphoma Kinase Positive (ALK+) Non–Small Cell Lung Cancer (NSCLC) Treated With Brigatinib in the Front-Line (FL) Setting in the United States: A Claims Database Analysis" published on 31 Mar 2023 by National Comprehensive Cancer Network.

HSD77 Real-World Dosing Patterns of Eculizumab-Naive and Eculizumab-Experienced Patients with Paroxysmal Nocturnal Hemoglobinuria Receiving Ravulizumab in the US

Treatment of paroxysmal nocturnal hemoglobinuria (PNH) includes C5 complement inhibitors ravulizumab and eculizumab. Ravulizumab dosing varies by weight and includes a loading dose, followed by maintenance doses given every 8 weeks via intravenous infusion. This study investigated real-world dosing patterns of eculizumab-naive and eculizumab-experienced patients with PNH receiving ravulizumab.

Real-World Eculizumab Dosing Patterns Among Patients with Paroxysmal Nocturnal Hemoglobinuria in a US Population.

PurposeCurrent pharmacologic management of paroxysmal nocturnal hemoglobinuria (PNH) consists of C5 inhibitors, eculizumab and ravulizumab; however, because patients experience incomplete symptom control, off-label doses may be utilized. We conducted a retrospective, longitudinal cohort study of provider-based claims data to assess the real-world eculizumab dosing patterns in PNH patients.Patients and MethodsPatients were ≥12 years, received ≥2 eculizumab infusions between January 1, 2015 and September 30, 2019, and had ≥3 months of continuous clinical activity prior to index. The index date was the first claim for eculizumab. Patients with ≥1 diagnosis of another indication for eculizumab were excluded. Treatment patterns including the proportion with high, label-recommended, and low dosages during induction (first 28 days) and maintenance (beginning day 29) phases were described. The proportion and time-to-first dose escalation, defined as an increase in dose or frequency of infusion, were assessed among a subset of patients (ie, escalation analysis cohort).ResultsA total of 707 patients were examined. Mean (standard deviation [SD]) starting dose was 862mg (412mg) and was higher than label-recommended 600mg for 64% of the patients. Mean (SD) dose per infusion was 859mg (391mg) during the induction phase; average dose was higher than label-recommended 600mg for 68%. Mean (SD) dose per infusion during the maintenance phase was 1005mg (335mg); average dose was higher than label-recommended 900mg for 43%. Dose escalation occurred in 40/121 escalation analysis cohort patients. Median time-to-first dose escalation was ~12 months.ConclusionResults suggest that deviations from label-recommended dosing patterns were common. Future budget impact assessments of eculizumab should account for real-world dosing patterns to comprehensively assess costs and benefits.

Real-World Ravulizumab Dosing Patterns Among Patients with Paroxysmal Nocturnal Hemoglobinuria in a US Population

Introduction: Current management of patients diagnosed with paroxysmal nocturnal hemoglobinuria (PNH) includes C5 complement inhibitors such as ravulizumab. The ravulizumab dosage regimen varies by patient body weight and consists of a single loading dose followed by maintenance doses administered every 8 weeks via intravenous infusion (see Table for label-recommended loading and maintenance dosing regimens by patient body weight category). Given its recent 2018 FDA approval, real-world data on the dosing patterns of ravulizumab are limited. This study investigated the real-world dosing patterns of patients with PNH treated with ravulizumab in a large US population.Methods: This retrospective longitudinal cohort study was conducted using provider-based claims data from the Symphony Health Integrated Dataverse ® (IDV). Patients were ≥12 years of age and received ≥2 infusions of ravulizumab between June 21, 2019 and May 6, 2021. The index date was defined as the 1st medical claim for ravulizumab infusion with ≥6 months of continuous clinical activity prior to the index (the baseline period). Patients with ≥1 diagnosis of atypical hemolytic uremic syndrome (another indication for ravulizumab) during the baseline period or on the index date were excluded to identify those with PNH. Patient baseline demographic and clinical characteristics including PNH-related comorbidities and symptoms were described. Because Symphony IDV does not record patient weight, it was assumed that all patients had a weight ≥60 and <100 kg (ie, “medium body weight”), consistent with mean weights reported in recent clinical trials of ravulizumab (~70 kg) and in the US population (men: 91 kg; women: 77 kg). Mean and mode loading and maintenance doses as well as the proportion of patients with high, label-recommended, and low loading and mean maintenance doses were calculated. To test the weight assumptions, 2 sets of sensitivity analyses were carried out to account for alternative dosing pattern scenarios, with all patients classified as “low body weight” (≥40 and <60 kg) or “high body weight” (≥100 kg).Results: A total of 433 patients with PNH were included in the study; the mean age was 47 years and 52% were female. The mean treatment period was 11.8 months; and 54%, 40%, and 6% of patients initiated ravulizumab in 2019, 2020, and 2021, respectively. Most patients (76%) were insured through a commercial insurance plan. Aplastic anemia and myelodysplastic syndrome were present at baseline in 22% and 5% of patients, respectively. The most frequent comorbidities were coagulopathy (13%), deficiency anemias (12%), and hypertension (11%); and 40% of patients had anemia (other than aplastic anemia) at baseline. Prior to initiating ravulizumab, 42% of patients had previously received ≥1 infusion of eculizumab during the baseline period. The mean (standard deviation [SD]) and mode loading doses were 3,316 (2,932) and 3,300 mg, respectively. The proportion of patients with a high, label-recommended, and low loading dose was 59%, 28%, and 13%, respectively (Table). During the maintenance phase, the mean (SD) and mode doses were 3,404 (1,024) and 3,300 mg, respectively; the proportion of patients with a high, label-recommended, and low mean dose during this phase was 27%, 51%, and 23%, respectively (Table). The sensitivity analyses revealed similar trends: nearly half or more than half of patients received a high loading dose; the proportion with a high mean dose during the maintenance phase was substantial when it was assumed that all patients had “low body weight” and negligible when assuming “high body weight” (Table).Conclusions: Most patients with PNH treated with ravulizumab received a higher than label-recommended loading dose regardless of weight category. Additionally, the mean dose received during the maintenance phase was higher than the label-recommended dose of 3,300 mg in more than one-quarter of patients (≥60 - <100 kg). The deviations from label-recommended dosing regimens-especially dosages exceeding recommendations-suggest that in some patients, PNH is not controlled by ravulizumab. Alternative weight scenarios will be tested in future analyses to account for weight distribution in the US. Future budget impact analyses of ravulizumab in patients with PNH should consider real-world dosing patterns in order to determine cost vs benefit. [Display omitted] DisclosuresCheng: Novartis: Other: I am an employee of Analysis Group, a consulting company that received funding from Novartis for this research study.. Fishman: Apellis: Current Employment, Current equity holder in publicly-traded company. Sarda: Apellis: Current Employment, Current equity holder in publicly-traded company. Krishnan: Apellis: Current Employment, Current equity holder in publicly-traded company. Kunzweiler: Apellis: Other: Employee of Analysis Group, Inc., Research Funding. Vu: Apellis: Other: Employee of Analysis Group, Inc., Research Funding. Yenikomshian: Apellis: Other: Employee of Analysis Group, Inc., Research Funding. Duh: Novartis: Other: I am an employee of Analysis Group, a consulting company that received funding from Novartis for this research study..

P84.11 Real-World Brigatinib Dosing Patterns in Patients with Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer in the United States

Standard dosing of brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor for treating ALK+ non-small cell lung cancer is 90 mg once daily for 7 days then escalated to 180 mg on Day 8 as tolerated. Among patients receiving this standard dose, 29% in the post-crizotinib ALTA trial and 38% in the tyrosine kinase inhibitor (TKI)-naïve ALTA-1L trial required a dose reduction. Asymptomatic laboratory abnormalities including creatine phosphokinase, amylase or lipase elevations were common causes of dose reductions in these studies. Outside of trial protocol mandated dosing, real-world dosing patterns of brigatinib have not been previously described. Adult (≥18 years) patients with ≥1 claim for brigatinib were identified between 01 April 2017 and 31 August 2019 from the IQVIA longitudinal pharmacy claims database and followed until the earliest of: dose reduction, treatment discontinuation, or end of follow-up. Average daily dose (ADD) was calculated as the product of pill strength and quantity of pills dispensed divided by the day supply. Dose reduction was defined as ≥30 days of supply with ADD < 180 mg/day after reaching 180 mg/day, or < maximum (max) dose in patients who did not reach 180 mg/day. Time to dose reduction from 180 mg/day or max dose and probability of continued therapy at ≥180 mg/day or max dose were assessed via Kaplan-Meier analysis. Adherence was defined using medication possession ratio (MPR) and dose compliance score (DCS) was calculated as total dosage received divided by total dosage expected. A total of 240 brigatinib patients were identified. Median age was 58 years, 57.9% were female and 85.4% had ≥1 prior TKI. Mean (standard deviation) follow-up time was 10.7 (7.6) months. A dose of 180 mg/day was achieved in 202 (84.2%) patients, of which 87.1% were treated after 1+ prior lines. Dose reduction occurred in 15.8% of patients who reached 180 mg/day, and the probability of continued therapy at ≥180 mg/day in patients still on therapy at 3 and 6 months after dose escalation was 89.5% and 86.0%, respectively. Of the patients with dose reduction, 43.8% reduced to 120 mg/day. A total of 38 (15.8%) patients did not reach 180 mg/day. Dose reduction occurred in 13.2% of these patients, and the probability of continued therapy at the max dose at 3 and 6 months after max dose was reached was 94.1% and 89.8%, respectively. Among the patients with dose reduction, 40.0% reduced to 90 mg/day. Adherence and dose compliance were high overall with 93.3% of patients having MPR > 80% and median DCS of 1.0 (0.3-2.2). Real-world data suggest that standard dose escalation (90 to 180 mg) occurs in most brigatinib patients (>84%) and that dose reduction rates may be lower outside the protocol mandated confines of clinical trials. Adherence and dose compliance were high. Analysis with longer follow-up time may be warranted to further evaluate these findings.

Real-World Eculizumab Dosing Patterns Among Patients with Paroxysmal Nocturnal Hemoglobinuria in a US Population

INTRODUCTION Current pharmacologic management of patients who are diagnosed with paroxysmal nocturnal hemoglobinuria (PNH) includes C5 complement inhibitors, such as eculizumab. The standard dosage of eculizumab, administered via intravenous infusion, is 600 mg/week for the first 4 weeks (induction phase), 900 mg for the fifth dose 1 week later, and 900 mg biweekly thereafter (maintenance phase). There is limited information describing dosing patterns of eculizumab in clinical practice. The purpose of this study was to conduct a comprehensive assessment of the real-world dosing patterns of patients with PNH treated with eculizumab in a large US population. METHODS A retrospective longitudinal cohort study using provider-based claims data from the Symphony Health Integrated Dataverse® was conducted. Patients were ≥12 years of age and received ≥2 infusions of eculizumab between October 1, 2014, and September 30, 2019. The index date was defined as the first medical claim for eculizumab infusion with ≥3 months of prior continuous clinical activity, defined as ≥1 claim of any type per quarter (ie, the baseline period). Patients with ≥1 diagnosis of another indication for eculizumab, including atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder, during the baseline period or on the index date were excluded to identify patients with PNH. Patient baseline demographic and clinical characteristics, including PNH-related comorbidities and PNH-symptoms, were described. Mean starting dose and the proportion with high (&amp;gt;600 mg), label-recommended (600 mg), and low (&amp;lt;600 mg) starting dose during the induction phase were calculated. In addition, the mean and mode dose during the induction and maintenance phases, as well as the proportion of patients with high, label-recommended, and low mean dose during the induction and maintenance phases, were described. RESULTS A total of 707 patients with PNH who had ≥2 infusions of eculizumab during the study period were included in this analysis; mean observation period was 23.9 months. Mean age was 45.4 years, 55.7% were female, and 35.9% were from the South. The majority of patients (77.1%) were insured through a commercial insurance plan. Respectively, 32.5% and 6.8% of patients had a diagnosis for aplastic anemia and myelodysplastic syndrome during baseline. The most frequent comorbidities in this sample included hypertension (26.6%), coagulopathy (26.6%), and renal failure (20.5%). In addition, 85.1% of patients experienced anemia (other than aplastic anemia) at baseline. The mean (standard deviation) starting dose during the induction phase was 862 (412) mg; the proportion of patients with high, label-recommended, and low starting dose was 64.1%, 30.6%, and 5.4%, respectively. The mean (standard deviation) and mode dose was 859 (391) mg and 900 mg during the induction phase, and 1011 (333) mg and 900 mg during the maintenance phase. Respectively, 67.9%, 25.9%, and 6.2% of patients had a high, label-recommended, and low mean dose during the induction phase, and 45.9%, 41.6%, and 12.5% had a high, label-recommended, and low mean dose during the maintenance phase. CONCLUSIONS This study demonstrates that the majority of patients with PNH treated with eculizumab were started on a dose in the induction phase that was higher than the label-recommended dose of 600 mg, and the mean dose received during the maintenance phase was higher than the label-recommended dose of 900 mg in approximately half of all patients. Future analyses that investigate budget impact of eculizumab in patients with PNH should account for real-world dosing patterns in order to comprehensively assess costs and benefits. Disclosures Cheng: Apellis: Research Funding. Sarda:Apellis: Current Employment, Current equity holder in publicly-traded company. Mody-Patel:Apellis: Current Employment, Current equity holder in publicly-traded company. Krishnan:Apellis: Current Employment, Current equity holder in publicly-traded company. Yenikomshian:Apellis: Research Funding. Scoble:Apellis: Current Employment, Current equity holder in publicly-traded company. Kunzweiler:Apellis: Research Funding. Vu:Apellis: Research Funding. Cheung:Apellis: Research Funding. Duh:Merck: Research Funding; Pharmacyclics: Research Funding; Takeda Oncology: Research Funding; GlaxoSmithKline: Research Funding; AstraZeneca: Research Funding; Blueprint Medicine: Research Funding; Novartis: Research Funding; Shire: Research Funding; Apellis: Research Funding.

Daratumumab Dose Analysis Among Patients with Multiple Myeloma in a US Community Oncology Setting: A Retrospective Observational Study in Integra Connect Network

BACKGROUND Since the FDA's initial indication for the use of daratumumab in relapsed/refractory multiple myeloma (RRMM) in November 2015, usage has been expanded by subsequent approvals in newly diagnosed, transplant-ineligible MM patients, and more recently in newly diagnosed transplant-eligible patients. Real World Data (RWD) has been published demonstrating daratumumab's efficacy in RRMM settings[1]and its utility of split dosing for the initial dose[2]. However, no study has been published to examine the real-world dosing patterns of daratumumab compared to the FDA standard dosing schedule. While there are minimal variations in the approved dosing schedule of daratumumab, generally accepted dosing is weekly in week 1 through week 8, q 2 Wks in week 9 through week 24, and q 4 Wks after week 24, all at the standard 16 mg/kg dosage[3]. In its approved dosing schedule, adjustments are made in the frequency of administration, but not in the standard weight-based dosing. METHODS Utilizing the Integra Connect database which contains 17 community oncology network accounts and over 1,900 providers in US, we collected all MM patients treated with daratumumab between January 1, 2016 and March 31, 2020. We then excluded any patient whose first line of therapy (LOT) was ambiguous, in order to correctly identify the daratumumab-containing LOTs. We also excluded LOT 1 daratumumab transplant induction due to the wide variation in daratumumab dosing schedules in clinical trials in the transplant eligible patient[4]. LOTs were determined based on International Myeloma Working Group guidelines[5]. Data were collected on the date of each individual daratumumab administration, counting initial split dose, if utilized, as 1 dose. The duration of daratumumab and number of doses administered were calculated and corrected for any time on treatment breaks. The study was conducted per individual patient by LOT cohorts, and for the entire cohort of patients. We utilized the standard dose schedule for daratumumab noted above to establish the expected doses of daratumumab and calculated the compliance dose ratio (ratio of actual doses to expected doses per time on therapy) to evaluate how closely real-world treatment adhered to the standard dosing schedule. RESULTS 1037 MM patients were included with at least 6 doses of daratumumab administration and without stem cell transplant or uncertain LOT. Across all LOTs, the mean duration of daratumumab treatment was 5.6 months with a median duration of 9.8 months. After week twenty-four, 671 (65%) patients remained on daratumumab-containing regimens, with 330 patients continuing q 1 Wk or q 2 Wks dosing, whereas the standard would employ a switch to q 4 Wks dosing (Figure 1). Overall compliance dose ratio was consistently above 100%, implying a significant proportion of patients were receiving more frequent dosing than expected under the standard dosing schedule (Figure 2). We carefully evaluated patients in various LOTs and combination therapies. Drug combination was not found to exert a significant impact on the daratumumab dosing pattern. Compliance dose ratio of daratumumab is slightly higher in RRMM compared to the dose ratio in LOT 1 newly diagnosed MM, but even LOT 1 has a ratio greater than 1 (Figure 3). It should be noted that this increased compliance dose ratio is present in all LOT cohorts despite 25% of patients being started on doses less frequent than weekly (Figure 1). CONCLUSIONS In real-world community oncology practices, daratumumab is utilized in a more frequent dosing schedule than the FDA approved standard dosing. With standard dosing there are 23 daratumumab doses in the first 52 weeks. The compliance dose ratio found in our RWD implies 27.3 doses in the first year for the entire cohort and 26.9 and 28.3 doses in LOTs 2 and 3 respectively. Thus, significantly increased drug and administrative costs are incurred over those anticipated in respect to daratumumab dosing utilization. This study is limited to the EMR and administrative claims data of those individuals who are being treated in a community oncology setting. Residual confounding and bias may exist due to entry error and unobserved patient characteristics.

MPN-070: Real-World Dosing Patterns of Ruxolitinib in Patients with Polycythemia Vera Who are Resistant to or Intolerant of Hydroxyurea

Context: Up to 40% of patients with polycythemia vera (PV) become resistant and/or intolerant to hydroxyurea. Ruxolitinib, a Janus kinase 1 and 2 inhibitor, is currently the only FDA-approved treatment for patients with hydroxyurea-resistant/intolerant PV. Objective: To characterize the reasons patients were switched from hydroxyurea to ruxolitinib and describe real-world dosing patterns of ruxolitinib in patients with PV. Design, Setting, and Patients: This retrospective medical chart review was conducted at US community hematology/oncology practices in the Cardinal Health Oncology Provider Extended Network. Eligible patients were ≥18 years old, initiated ruxolitinib during the index period (01 Jan, 2015–31 Dec, 2016), had previously received hydroxyurea for ≥3 months, and were seen ≥2 times over 6 months post–ruxolitinib initiation. Data were collected for 12 months prior to ruxolitinib initiation, near ruxolitinib initiation, and until the last provider visit. Main Outcomes and Measures: Clinical characteristics including blood counts, symptoms, phlebotomy, and ruxolitinib treatment patterns Results: Providers identified 249 patients for inclusion. Primary causes of hydroxyurea discontinuation were resistance (78%), intolerance (28%), patient choice (23%), and other (4%); 14% were both resistant and intolerant. The most frequent reasons for hydroxyurea discontinuation due to resistance were hematocrit ≥45% (79%), symptoms (63%), leukocytosis (38%), and thrombocytosis (38%). The most frequent intolerance signs/symptoms were nausea/vomiting (50%), stomatitis (37%), skin ulcers (23%), and fever (9%). One-hundred thirty-one patients (53%) initiated ruxolitinib at 10 mg twice daily (BID; recommended dose); median (range) treatment duration was 29.2 (11.2–37.1) months. Of these patients, 35 (27%) required dose modification (increase, n=24; decrease, n=11) within the first 6 months; 4 patients had interruptions. The most common reasons for dose increase were continued need for phlebotomy (46%) and persistent symptoms (38%); 6 patients had dose reductions owing to reduced platelets. 12% of patients required dose modifications after 6 months. Hematocrit control (hematocrit Conclusions: Among patients with PV who switched from hydroxyurea to ruxolitinib, approximately half initiated ruxolitinib at the recommended dose (10 mg BID). Of these patients, 27% experienced dosing modifications within the first 6 months; need for modification decreased over time.

Pharmaco-utilization of biologic drugs in patients affected by psoriasis, psoriatic arthritis and ankylosing spondylitis in an Italian real-world setting

ABSTRACT Background As primary aim the study evaluated the monthly average dose for biologic drugs used for psoriasis (PSO), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) in real-world settings. Methods This retrospective analysis was based on administrative databases of Italian Entities. Adult patients diagnosed PSO, PsA or AS with ≥1 prescription of biologic drugs indicated for these diseases were included during 01/01/2011 – 30/06/2017. Monthly average dose and persistence were evaluated during 6-months after inclusion (follow-up). Results Overall, 6,179 patients prescribed biologic drugs were included: 2,373 represented the 1.1% of PSO-patients, 2,756 the 37.4% of PsA-patients, 1,050 the 17.8% of AS-patients. Monthly average dose was: 69 mg (PSO), 73 mg (PsA), 70 mg (AS) for adalimumab; 152 mg (PSO), 155 mg (PsA), 147 mg (AS) for etanercept; 140 mg (PSO), 133 mg (PsA), 166 mg (AS) for infliximab; 255 mg (PSO), 183 mg (PsA), 154 mg (AS) for secukinumab. Persistance to adalimumab was 76%(PSO), 78%(PsA), 74%(AS); with etanercept 77% in each disease-cohort; with infliximab 67%(PSO), 71%(PsA), 88%(AS); with secukinumab 91%(PSO) and 85%(PsA). Conclusion The study described real-world dosing patterns of biologics indicated for PSO, PsA, or AS, suggesting a trend of monthly average dose generally lower than the dosage indicated in the datasheet.

Real-World Dosing Patterns and Outcomes of Patients With Metastatic Pancreatic Cancer Treated With a Liposomal Irinotecan Regimen in the United States.

Liposomal irinotecan (nal-IRI) is a topoisomerase inhibitor proven to improve survival in metastatic pancreatic cancer (mPC). This study describes real-world characteristics of patients treated with nal-IRI for mPC. Patients 18 years or older diagnosed with stage IV mPC and treated with nal-IRI were selected retrospectively from a deidentified electronic health record database of more than 2 million US cancer patients. Demographics, clinical and dosing characteristics, and treatment outcomes were collected. Of 257 total patients, 145 (57%) received nal-IRI as first- or second-line therapy. Median nal-IRI treatment duration was 51 days, longer when nal-IRI was used as first/second versus as third-line therapy or later (62 vs 44.5 days). Seventy patients (27.2%) experienced dose modification. Median time to treatment discontinuation was 2.3 versus 1.6 months for first-/second- versus third-line therapy or later, respectively. Median overall survival from nal-IRI initiation was 5.6 versus 4.1 months for first-/second- versus third-line therapy or later, respectively. Prior irinotecan treatment, baseline serum albumin less than 40 g/L, and baseline neutrophil-to-lymphocyte ratio greater than 5 were associated with reduced overall survival. This is the first large US study of real-world US mPC patients treated with nal-IRI. These results, comparable to the NAPOLI-1 trial, can help inform future studies and the efficacy of nal-IRI in mPC therapy.

Real-World Dosing Patterns of Ruxolitinib in Patients with Polycythemia Vera Who Are Resistant to or Intolerant of Hydroxyurea

Background Polycythemia vera (PV) is a myeloproliferative neoplasm affecting &gt;100,000 people in the United States annually. Patients (pts) with PV are at risk for thromboembolic events (TEs), premature death, and high symptom burden. Hydroxyurea (HU) is recommended for high-risk pts with PV; however, up to 40% of pts become resistant and/or intolerant to the drug (Demuynck T, et al. Ann Hematol. 2019;98:1421-1426). Ruxolitinib (RUX), a Janus kinase (JAK) 1/JAK2 inhibitor, is currently the only FDA-approved treatment option for pts with PV who are resistant to or intolerant of HU. We conducted a retrospective chart review to characterize the reasons pts were switched from HU to RUX and to describe the real-world dosing patterns of RUX in pts with PV. Methods This retrospective medical chart review was conducted at US community hematology/oncology practices in the Cardinal Health Oncology Provider Extended Network. Eligible pts were ≥18 y old, initiated RUX therapy during the index period (January 1, 2015, to December 31, 2016), were previously treated with HU for ≥3 mo, and were seen at least twice during the 6 mo following RUX initiation. Data were collected for the 12 mo prior to RUX initiation (including near the time of HU discontinuation), near the time of RUX initiation (index), and up to the last provider visit. Pt and clinical characteristics were collected, including blood counts, symptoms, TEs, cardiovascular disease risk factors, phlebotomy, and HU and RUX treatment patterns. Target enrollment was 250 pts; interim results are presented here. Results Providers identified 99 pts for inclusion; mean (SD) age was 64 (9.9) y, 56% were male, and 68% had high-risk PV (ie, age ≥60 y and/or history of TE). All pts had been tested for the JAK2V617F mutation, and 99% were positive. At the time of HU discontinuation, 28% of pts had reached an HU dose of ≥2 g/d; median (range) HU treatment duration was 9.7 (3.6-182.4) mo. Causes of HU discontinuation were resistance (63%), intolerance (17%), resistance and intolerance (11%), and other reasons (9%; Table). The most frequent reasons for HU discontinuation due to resistance were hematocrit (Hct) ≥45% (79%), symptoms (45%), leukocytosis (32%), thrombocytosis (31%), and splenomegaly (22%). The most frequent intolerance signs and symptoms were nausea (43%), stomatitis (25%), fever (18%), and skin ulcers (14%). With respect to the RUX starting dose, 44 pts (44%) initiated RUX at the US package insert-recommended dose of 10 mg twice daily (BID); median (range) treatment duration for these pts was 26.4 (3.2-52.0) mo (Table). During the first 6 mo of RUX treatment, dose modification was noted in 19 pts (43%) who initiated at 10 mg BID (dose increase, n=13 [30%]; dose decrease, n=5 [11%]; dose interruption, n=1 [2%]). The most common reasons for dose increase were continued need for phlebotomy (39%) and symptoms (39%). Five pts required a dose reduction; the most common reason was low hemoglobin levels (n=3). Overall, pts starting at 10 mg BID had more dose modifications in the first 6 mo of RUX treatment (43%), with fewer dose modifications needed after 6 mo (25%). Hct control (Hct &lt;45%) at initiation and after 6 mo of RUX treatment was 14% and 75%, respectively. At the time of the last visit, 48% of pts were still taking RUX. The majority of pts (65%) who discontinued RUX had no dosing changes from the time of initiation to discontinuation. Conclusions In this interim analysis of real-world data pertaining to pts with PV who discontinued HU and were subsequently treated with RUX, the most common resistance events leading to HU discontinuation were Hct ≥45%, uncontrolled symptoms, leukocytosis, thrombocytosis, and splenomegaly. Discontinuations due to intolerance were most commonly attributed to nausea, stomatitis, fever, and skin ulcers. Of pts who were switched from HU to RUX, the duration of HU treatment was shorter and the proportion of pts treated with HU doses of ≥2 g/d was higher than has been reported for all pts discontinuing HU, irrespective of their next line of therapy (Grunwald MR, et al. ASH Annual Meeting 2017. Poster 1633). Less than half of pts initiated RUX at the recommended dose of 10 mg BID; 41% of pts dosed in accordance with the recommended starting dose experienced dosing modifications (primarily dose increases); however, the majority of pts who discontinued RUX had no dosing modifications during their treatment. Results from the entire cohort of 250 pts will be presented. Disclosures Altomare: Amgen: Consultancy; Incyte: Consultancy, Speakers Bureau; Novartis: Consultancy; Rigel: Consultancy. Nguyen:Incyte: Employment, Equity Ownership. Parasuraman:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Kish:Cardinal Health: Employment. Lord:Cardinal Health: Employment, Equity Ownership. Colucci:Incyte: Employment, Equity Ownership.

Comparative analysis of US real-world dosing patterns and direct infusion-related costs for matched cohorts of rheumatoid arthritis patients treated with infliximab or intravenous golimumab.

PurposeThe objectives of this study were to evaluate and compare treatment patterns and infusion-related health care resource expenditures for rheumatoid arthritis (RA) patients initiating golimumab for intravenous use (GLM-IV) and infliximab (IFX) therapy and to assess cost implications from the commercial perspective.MethodsAdult RA patients with a new episode of GLM-IV or IFX treatment between Janu-ary 1, 2014 and March 31, 2016 were identified from MarketScan databases and evaluated for maintenance infusion intervals and related costs of treatment. IFX and GLM-IV patients were matched 1:1 on index medication treatment duration, gender, payer type, prior biologic use, and post-index methotrexate use. Paid amounts for drugs and associated administration costs were applied to treatment group dosing patterns.ResultsFinal matched treatment groups included 547 GLM-IV and 547 IFX patients (mean age = 55–56 years). Mean (SD) follow-up was 609 (161) days for GLM-IV and 613 (163) days for IFX. Treatment duration was 396 (240) days for GLM-IV and 397 (239) days for IFX. Overall, 80% of GLM-IV and 39% of IFX maintenance infusions were given approximately every 8 weeks; and 6% of GLM-IV and 53% of IFX maintenance infusions occurred more frequently than every 8 weeks (P<0.001). When weighting of the maintenance infusion interval was applied, the mean number of induction plus maintenance infusions during the first year of treatment was estimated at 7.03 for GLM-IV and 9.48 for IFX. From the commercial perspective, drug plus administration costs per infusion were $5,846 for GLM-IV and $5,444 for IFX with total annual cost of therapy for GLM-IV patients costing $10,507 less than that for IFX patients in the first year and $6,774 less than that for IFX patients in subsequent years.ConclusionAnnual GLM-IV drug plus administration costs for commercial health plans were significantly less than IFX in RA patients due to differences in real-world dosing and administration.

735P - Real-world dosing patterns of patients (pts) with metastatic pancreatic cancer (mPC) treated with liposomal irinotecan (nal-IRI) in US oncology clinics

735P - Real-world dosing patterns of patients (pts) with metastatic pancreatic cancer (mPC) treated with liposomal irinotecan (nal-IRI) in US oncology clinics