Comparing FOLFOX delivery in trial and real-world populations using longitudinal cumulative dose.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1521-1521
Author(s):  
Michael Webster-Clark ◽  
Hanna Kelly Sanoff ◽  
Alexander P. Keil ◽  
Til Sturmer ◽  
Daniel Westreich ◽  
...  
Keyword(s):  
Cumulative Dose ◽  
Real World ◽  
Treatment Delivery ◽  
End Of Treatment ◽  
Number Of Patients ◽  
The Us ◽  
Versus Trial ◽  
Trial Participants ◽  
Dose Reductions ◽  
Over Time

1521 Background: Patterns of chemotherapy delivery are likely to differ between trial and real-world populations. Typical measures used to compare these patterns are calculated at treatment completion, potentially missing key differences in the timing and trajectory of delays and dose reductions. We used a new measure, longitudinal cumulative dose (LCD), to compare treatment delivery over time in trial and real-world populations. Methods: We compared chemotherapy delivery in patients with stage II-III colon cancer enrolled in the MOSAIC trial of 5-fluorouracil (5FU) vs oxaliplatin + 5FU (FOLFOX4) to patients treated from 2008-2019 in the US Oncology Network with FOLFOX4, FOLFOX6, or mFOLFOX6. For each patient, we computed oxaliplatin LCD as the cumulative oxaliplatin dose received at a given timepoint (t) divided by the final standard oxaliplatin dose. We then estimated the median and 25th and 75th percentiles for oxaliplatin LCD within each regimen at day 68 (before the standard timing of the 7th dose), 168 (two weeks after the standard end of treatment), and 250. Results: The table shows the number of patients receiving each treatment regimen and the median and interquartile range for oxaliplatin LCD at each time. Higher LCDs in the trial show delivery closer to standard treatment, meaning fewer delays, dose reductions, and discontinuations. Differences between the medians, 25th percentiles, and 75th percentiles of LCD in each regimen were small at day 68 but grew considerably by days 168 and 250. Conclusions: Divergence from the standard dosing schedule was larger in real-world versus trial settings and varied by oxaliplatin regimen. LCD, as a longitudinal measure, showed that differences in delivery between trial and real-world populations grew substantially over time (even after 168 days and the standard end of treatment) possibly as real-world patients experienced more side effects and barriers to treatment than trial participants. These discrepancies in LCD may cause poorer outcomes in real-world settings than expected based on randomized trials.[Table: see text]

Longitudinal cumulative dose: A novel measure to assess multiple dimensions of chemotherapy adherence over time.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3522-3522
Author(s):  
Michael Webster-Clark ◽  
Alexander P Keil ◽  
Hanna Kelly Sanoff ◽  
Til Sturmer ◽  
Daniel Westreich ◽  
...  
Keyword(s):  
Cumulative Dose ◽  
Standard Dose ◽  
Performance Status ◽  
Dose Intensity ◽  
International Study ◽  
Standard Regimen ◽  
Number Of Patients ◽  
And Performance ◽  
The Impact ◽  
Over Time

3522 Background: Adjuvant chemotherapy regimens take months to complete. Despite this, trials and observational studies evaluate chemotherapy adherence via measures assessed at the end of treatment (e.g. number of patients missing any dose, relative dose intensity [RDI]). This approach misses information that impacts outcomes, like treatment delays. We propose longitudinal cumulative dose (LCD) as a way to integrate the impact of dose reductions, missed doses, and dose delays at each cycle over time. Methods: We obtained data from the 2,246 participants in the Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer (MOSAIC). We evaluated proportions of patients stopping treatment early and reducing (based on protocol), missing, or delaying a dose in each arm for each chemo agent at each visit. We obtained LCD, the fraction of the final standard dose a participant reached by a given day, for each participant and each chemo agent. We compared LCD medians over time and at the end of a standard regimen (24 weeks) between treatment arms and by age and performance status. We assessed agreement between oxaliplatin LCD and RDI with Fleiss’ kappa (Table). Results: Participants randomized to FOLFOX were more likely than those randomized to 5FU to stop treatment, reduce doses, miss doses, or delay visits; these differences increased over time. Median LCD for oxaliplatin in the FOLFOX arm at 24 weeks was 77%. Graphs of median LCD for 5FU showed a clear difference between arms (FOLFOX arm median LCD: 81%; 5FU arm median LCD, 96%). While 5FU LCD decreased with age in the FOLFOX arm (median LCD in those age <40: 85%; 40-64, 82%; 65-75, 76%), it was similar across ages in the 5FU arm (median LCD 94%, 96%, and 96%, respectively), with smaller performance status trends. RDI and LCD showed fair agreement (Fleiss’ kappa=0.34); 19% of those with RDI over 85% had LCD under 60%. Conclusions: Visualizing LCD highlighted the timing and scale of deviations from standard administration, with major differences in 5FU LCD across arms. Next steps include evaluating if LCD predicts clinical outcomes. [Table: see text]

Real-world dosing, management, and clinical outcomes of patients (pts) with metastatic pancreatic adenocarcinoma (mPDAC) treated with liposomal irinotecan.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16780-e16780
Author(s):  
Laith I. Abushahin ◽  
Paul Cockrum ◽  
Andy Surinach ◽  
Bruce Belanger
Keyword(s):  
Real World ◽  
Relative Survival ◽  
The United States ◽  
Duration Of Treatment ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Starting Dose ◽  
The Us ◽  
Liposomal Irinotecan ◽  
To Receive ◽  
Dose Reductions

e16780 Background: Pancreatic cancer remains one of the most lethal cancers in the United States (US) with a 5-year relative survival of 10%. Liposomal irinotecan is a topoisomerase inhibitor indicated, in combination with 5-fluorouracil and leucovorin, for pts with mPDAC following disease progression on gemcitabine-based therapy. This study examines the real-world use and therapeutic management of pts with mPDAC treated with liposomal irinotecan. Methods: This retrospective observational study utilized the Flatiron Health EHR-derived de-identified database from over 280 cancer clinics in the US. Data were analyzed for adult pts with mPDAC treated with liposomal irinotecan based regimens between Nov 2015 and Oct 2019. Pts were categorized into two starting dose groups: 70mg/m2 and < 65mg/m2. Pt characteristics, overall survival (OS), duration of treatment (DOT), and impact of dose reductions (DR, reduction ≥ 7mg/m2) were assessed among pts who received ≥3 cycles of treatment (tx). Results: Of the 532 pts (median age: 69y, IQR: 62-75) included in the study, 95 (18%) had an ECOG score of 2+ at tx initiation. Of the 184 pts (69y, 42 – 84) that did not receive 3 cycles of tx, 47 (25%) had an ECOG score of 2+ and 83 (45%) had two or more prior lines of tx. 348 pts (69y, 43 – 85) received ≥3 cycles of tx. 116 (33%) pts had two or more prior lines of tx, 209 (60%) had an ECOG score of 0-1, 48 (14%) had an ECOG score of 2+, and 91 (26%) had missing scores. 220 (63%) initiated tx at 70mg/m2 and 128 (37%) initiated at < 65mg/m2. 83 (38%) 70mg/m2 and 26 (20%) < 65mg/m2 pts experienced a DR during tx. 43 (52%) and 14 (54%) of the DRs occurred within the first 6 wks of tx in the 70mg/m2 and < 65mg/m2 cohorts, respectively. Median DOT was 12.6 weeks for 70mg/mg2 and 9.1 wks for < 65mg/m2 pts; DOT was longer among pts with a DR: 19.0 wks and 16.1 wks, respectively. Median OS (mOS) was 7.2 months (95% CI: 6.2 – 8.1) and 6.2 mos (5.0 – 7.4) for pts receiving 70mg/m2 and < 65mg/m2, respectively. mOS for pts with a DR was 8.9 mos (7.3 – 10.8) and 7.7 mos (5.0 – 14.9) for pts receiving 70mg/m2 and < 65mg/m2, respectively. mOS for pts with no DR was 6.0 mos (4.8 – 7.2) and 6.0 mos (4.7 - 7.2) for those receiving 70mg/m2 and < 65mg/m2, respectively. Conclusions: In this descriptive study among pts who were able to receive ≥3 cycles of liposomal irinotecan and remain on tx for ≥4 wks, DRs were effective in extending DOT and OS, independent of starting dose. The longest DOT and OS were observed in the pts who received 70mg/m2 with DRs. Pts who received 70mg/m2 and < 65mg/m2 had similar OS in the absence of DRs.

Real-World Ponatinib Prescribing Patterns and Outcomes in US Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1591-1591
Author(s):  
Michael J. Mauro ◽  
Lisa J. McGarry ◽  
Mo Yang ◽  
Stephanie Lustgarten ◽  
Hui Huang
Keyword(s):  
Dose Reduction ◽  
Real World ◽  
Dose Adjustment ◽  
Prescribing Patterns ◽  
Employment Equity ◽  
Line Therapy ◽  
Starting Dose ◽  
The Us ◽  
Equity Ownership ◽  
Over Time

Abstract Background: In Jan 2014, ponatinib was reintroduced to the US market after an 11 week withdrawal to review data on arterial thrombotic events, revise US prescribing information (USPI) and implement a risk evaluation and mitigation strategy (REMS). The USPI was revised to narrow the indicated population and recommend a starting dose of 45 mg, with consideration of 1) lower doses in patients with selected comorbidities or to manage adverse events, 2) dose reduction in chronic phase (CP) and accelerated phase (AP) chronic myeloid leukemia (CML) patients achieving major cytogenetic response, and 3) discontinuation if response has not occurred at 3 months. In the US, ponatinib is available exclusively through a specialty pharmacy that maintains prescribing data for all US ponatinib-treated patients since reintroduction. Examining these data provides insight into practitioners' patient selection and prescribing patterns, and real-world ponatinib outcomes. Methods: We performed a retrospective analysis of patients starting treatment with ponatinib between 01 January 2014 and 25 March 2015 using data from referring physicians, patient intake forms and pharmacy dispensing records. Patient and prescriber characteristics, and dosing and dose modifications were documented. Clinical, demographic and physician characteristics were examined as predictors of initial dose and dose modification using logistic regression; therapy duration was assessed using Kaplan-Meier techniques and proportional hazard regression. Results: 758 US patients initiated treatment with ponatinib over this 15-month period, (58% male; median age 55 years [range: 11-98]). Among 730 patients with a specified diagnosis, 80% had CML and 4% Philadelphia chromosome positive (Ph+) acute lymphocytic leukemia (ALL); the remainder had unspecified ALL (10%), other hematologic malignancies (3%), and solid tumors (3%). Of 411 CML patients reporting disease phase, 61% were in CP, 18% AP and 21% blast phase (BP). 12% of CML and 8% of Ph+ ALL patients had a reported T315I mutation. 21% of CP, 34% of AP, 12% of BP and 31% of Ph+ ALL patients were receiving ponatinib as 2nd-line therapy, with the remainder in 3rd line or later. Most recent prior TKI was dasatinib for 48%, nilotinib for 23%, bosutinib for 17%, and imatinib for 12% of patients in all therapy lines. 50% received 45 mg as their initial dose, 33% 30 mg and 17% 15 mg. Prescribers' practice setting was 49% community and 51% academic. Most prescribers (82%) had only 1 ponatinib patient; only 7% had 3 or more. Prescribers with >1 ponatinib patient were less likely to prescribe 45 mg starting dose (OR=0.53 for those with 2 patients; OR=0.25 for 3+ patients.) 23% of patients had at least one dose adjustment, including 17% with dose reduction. Among CP patients initially on 45 mg, with at least 6 months of therapy, 42% reduced dose (29% to 30 mg; 13% to 15 mg). Dose reduction decreased significantly for later therapy lines in CP, but did not differ by disease phase. Median time on therapy was >15 months for CP, 10.6 months for AP, 7.0 months for BP, and >14 months for Ph+ ALL. CP patients' time on therapy was longer for those started on 15 mg, although this difference was not significant (p=0.14) (Figure.) Reasons for dose adjustment and discontinuation were not well documented, but they appeared to occur at a relatively constant rate over time rather than at time points recommended for response monitoring. Conclusions: Real-world US data shows ponatinib is prescribed across disease phase, therapy line, and mutation status. While a majority of patients were in their 3rd line of therapy or later, a substantial proportion of patients, especially in AP CML and Ph+ ALL, received ponatinib as 2nd line therapy. Physicians appear to be selecting patients who are younger than those enrolled in registrational trial for ponatinib (55 years vs. PACE trial median age, 64 years), and mitigating against potential risk using lower starting doses and dose reduction. Most prescribers have only 1 ponatinib patient, but physicians with >1 ponatinib patient favor lower starting doses. Dose reduction and discontinuation occurred steadily over time rather than clustered at routine response milestone time points. CP CML Patients starting at 15 mg appear to have similar or better treatment duration compared with those started at higher doses. Disclosures Mauro: Ariad: Consultancy; Pfizer: Consultancy; Novartis Pharmaceutical Corporation: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. McGarry:ARIAD: Employment, Equity Ownership. Yang:ARIAD Pharmaceuticals, Inc: Employment. Lustgarten:ARIAD Pharmaceuticals Inc.: Employment, Equity Ownership, Other: Stock. Huang:ARIAD: Employment, Equity Ownership.

scholarly journals Effectiveness and safety of mepolizumab in combination with corticosteroids in patients with eosinophilic granulomatosis with polyangiitis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Masanobu Ueno ◽  
Ippei Miyagawa ◽  
Kazuhisa Nakano ◽  
Shigeru Iwata ◽  
Kentaro Hanami ◽  
...  
Keyword(s):  
Real World ◽  
Eosinophil Count ◽  
Granulomatosis With Polyangiitis ◽  
Remission Rate ◽  
Retention Rate ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Number Of Patients ◽  
Significant Difference ◽  
Eosinophilic Granulomatosis ◽  
Over Time

Abstract Background Mepolizumab (MPZ), an anti-interleukin-5 antibody, is effective for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). However, its effectiveness has not been adequately evaluated in real-world clinical practice. In this study, we assessed the effectiveness and safety of MPZ (300 mg) for relapsing/refractory EGPA resistant to corticosteroids (CS) for 1 year in real-world settings. Methods We administered MPZ (300 mg) to 16 patients with relapsing/refractory EGPA resistant to CS (Post-MPZ). We also retrospectively collected data from the same patients for the 12 months before the administration of MPZ (Pre-MPZ). The primary endpoint was the 12-month remission rate after MPZ administration and the secondary endpoints were the Birmingham vasculitis activity score (BVAS), vasculitis damage index (VDI), eosinophil counts, changes in concomitant CS doses/concomitant immunosuppressant use, MPZ retention rate, and incidence of adverse events. The clinical course was compared between Pre-MPZ and Post-MPZ. Results The 12-month remission rate after the initiation of MPZ was 75%. No change was observed in BVAS, eosinophil count, or concomitant CS dose over time in the Pre-MPZ group, whereas all these parameters were significantly decreased over time in the Post-MPZ group. The number of patients using concomitant immunosuppressant also decreased over time in the Post-MPZ group. VDI did not increase in either group. The MPZ retention rate was 100% and only three patients (18.8%) had infections. Changes in BVAS, eosinophil count, and cumulative concomitant CS dose were significantly lower in the Post-MPZ group than in the Pre-MPZ group. There was no significant difference in the changes in VDI between the groups. Conclusion This study demonstrated that MPZ is effective and safe for EGPA. Furthermore, MPZ decreases disease activity, increases remission rate, and has a CS-sparing effect.

Using randomized trial data to estimate effects of complex treatment regimens in real-world patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18706-e18706
Author(s):  
Michael Webster-Clark ◽  
Hanna Kelly Sanoff ◽  
Jennifer Leigh Lund ◽  
Til Sturmer ◽  
Daniel Westreich ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Real World ◽  
Target Population ◽  
Stage Iii ◽  
Covariate Data ◽  
Treatment Regimens ◽  
Stage Iii Colon Cancer ◽  
Specific Protocol ◽  
Trial Participants ◽  
Dose Reductions

e18706 Background: Real-world patients often differ from trial participants in prognostic factors such as age, sex, and cancer substage. New methods combine covariate data from real-world patients (the “target population”) with outcome and covariate data from a trial to estimate treatment effects in the target population that take these differences into account. With some assumptions, these methods can also estimate outcomes under treatment regimens not studied in the trial such as “what if we only gave six cycles of chemotherapy?” or “what if patients all perfectly followed a protocol?” Methods: Data from the MOSAIC trial of 5-fluorouracil (5FU) vs oxaliplatin + 5FU (FOLFOX) were combined with covariate data from a target population of stage III colon cancer patients in the US Oncology Network meeting trial eligibility criteria. We used weighting and G-computation to estimate five-year mortality and treatment-related paresthesia risk in the target population for four regimens: treatment with up to 12 cycles of 5FU, if providers used their discretion on dose reductions and delays (5FU-MD); up to 12 cycles of FOLFOX with similar physician discretion (FOLFOX-MD); up to 6 cycles of FOLFOX, with providers perfectly following a strict and specific protocol of dose reductions and delays (6-cycle FOLFOX-P, “P” for “per protocol”); and up to 12 cycles of FOLFOX, following the same strict protocol (12-cycle FOLFOX-P). Results: Tablepresents five-year all-cause mortality and paresthesia risk under each regimen in the stage III target population estimated from the models built in trial participants. Paresthesia risk increased with cumulative oxaliplatin dose. Estimated 5-year mortality was lowest with 12-cycle FOLFOX-P. Conclusions: In a target population of US Oncology Network patients with stage III colon cancer, strict protocols of 12 cycles of FOLFOX were predicted to improve survival compared to strict 6-cycle FOLFOX regimens or less strict 12-cycle FOLFOX and 5FU regimens at the cost of substantial increases in side effects. While estimates of risk differences in 5-year mortality were imprecise, combining trial and real-world data and then using weights and G-computation allowed estimation of benefits and harms of multiple regimens in a clinically relevant patient population.[Table: see text]

Recent trends in age at diagnosis of colon cancer in the United States, 2004-2015, a National Cancer Database study.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 490-490
Author(s):  
Boone Wilder Goodgame ◽  
Jack Virostko ◽  
Anna Capasso ◽  
Thomas Yankeelov
Keyword(s):  
Colorectal Cancer ◽  
Rural Areas ◽  
Urban Areas ◽  
Advanced Disease ◽  
The United States ◽  
National Cancer Database ◽  
Younger Adults ◽  
Number Of Patients ◽  
The Us ◽  
Over Time

490 Background: The incidence of colorectal cancer (CRC) in adults younger than age 50 has been increasing in the US since 1970. The US Preventive Services Task Force recommends screening for CRC beginning at age 50, while the American Cancer Society recently revised its guidelines to advise screening at age 45. We analyzed the National Cancer Database (NCDB) from 2004 through 2015 to determine whether the proportion of patients diagnosed younger than 50 has changed during this time. Methods: This was a retrospective study of NCDB data, which includes more than 70 percent of newly diagnosed cancer cases in the US. We examined the proportion of patients diagnosed prior to age 50 as our primary endpoint. We used the Cochran–Armitage test for trend to assess changes in the proportion of cases diagnosed at age < 50 years old as a function of year of diagnosis. Results: We identified 152,749 patients diagnosed under age 50 and 1,033,014 patients diagnosed at age 50 or greater. Over the study period, the proportion of the total number of patients diagnosed with colorectal cancer under age 50 increased (14.3% in 2015 vs. 11.5% in 2004, p < 0.0001). Younger adults with CRC presented with more advanced disease, with 49.9% stage III or IV disease, as compared to 40.0% in those diagnosed over age 50. Both men and women had a rising proportion of cases diagnosed younger than 50 (p < 0.0001) over time. In men, only non-Hispanic whites had an increase in diagnosis at ages less than 50 (p < 0.0001), while in women, all racial and ethnic subgroups had an increase in younger diagnoses over time (p < 0.01). All income quartiles (p < 0.001) demonstrated a proportional increase in younger adults over time, with the highest income quartile having the highest proportion of younger cases. The proportion of younger-onset CRC rose in urban areas (p < 0.001), but did not rise in rural areas. Conclusions: The proportion of persons diagnosed with CRC under age 50 in the US has continued to increase over the past decade. Younger adults presented with more advanced disease, suggesting that screening could improve outcomes.

scholarly journals Analysis of 220 Years of Floodplain Population Dynamics in the US at Different Spatial Scales

Water ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 141
Author(s):  
Firoza Akhter ◽  
Maurizio Mazzoleni ◽  
Luigia Brandimarte
Keyword(s):  
Population Dynamics ◽  
Large Scale ◽  
Spatial Scales ◽  
National Level ◽  
State Level ◽  
Economic Activities ◽  
Protection Measures ◽  
Management Planning ◽  
The Us ◽  
Over Time

In this study, we explore the long-term trends of floodplain population dynamics at different spatial scales in the contiguous United States (U.S.). We exploit different types of datasets from 1790–2010—i.e., decadal spatial distribution for the population density in the US, global floodplains dataset, large-scale data of flood occurrence and damage, and structural and nonstructural flood protection measures for the US. At the national level, we found that the population initially settled down within the floodplains and then spread across its territory over time. At the state level, we observed that flood damages and national protection measures might have contributed to a learning effect, which in turn, shaped the floodplain population dynamics over time. Finally, at the county level, other socio-economic factors such as local flood insurances, economic activities, and socio-political context may predominantly influence the dynamics. Our study shows that different influencing factors affect floodplain population dynamics at different spatial scales. These facts are crucial for a reliable development and implementation of flood risk management planning.

scholarly journals Real World Performance Evaluation of Transcatheter Aortic Valve Implantation

2021 ◽  
Vol 10 (9) ◽  
pp. 1890
Author(s):  
Gabriele Pesarini ◽  
Gabriele Venturi ◽  
Domenico Tavella ◽  
Leonardo Gottin ◽  
Mattia Lunardi ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Real World ◽  
Baseline Risk ◽  
Risk Scores ◽  
World Population ◽  
Control Analysis ◽  
Transcatheter Aortic Valve ◽  
Procedural Control ◽  
Risk Patients ◽  
Over Time

Background: The aim of this research is to describe the performance over time of transcatheter aortic valve implantations (TAVIs) in a high-volume center with a contemporary, real-world population. Methods: Patients referred for TAVIs at the University Hospital of Verona were prospectively enrolled. By cumulative sum failures analysis (CUSUM), procedural-control curves for standardized combined endpoints—as defined by the Valve Academic Research Consortium-2 (VARC-2)—were calculated and analyzed over time. Acceptable and unacceptable limits were derived from recent studies on TAVI in intermediate and low-risk patients to fit the higher required standards for current indications. Results: A total of 910 patients were included. Baseline risk scores significantly reduced over time. Complete procedural control was obtained after approximately 125 and 190 cases for device success and early safety standardized combined endpoints, respectively. High risk patients (STS ≥ 8) had poorer outcomes, especially in terms of VARC-2 clinical efficacy, and required a higher case load to maintain in-control and proficient procedures. Clinically relevant single endpoints were all influenced by operator’s experience as well. Conclusions: Quality-control analysis for contemporary TAVI interventions based on standardized endpoints suggests the need for relevant operator’s experience to achieve and maintain optimal clinical results, especially in higher-risk subjects.

scholarly journals POS0619 MODELLING OF DISEASE ACTIVITY IN PATIENTS WITH INFLAMMATORY ARTHROPATHIES TREATED WITH ETANERCEPT ORIGINATOR OR BIOSIMILAR AS FIRST-LINE BIOLOGIC IN AN AUSTRALIAN REAL-WORLD DATASET

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 547.1-547
Author(s):  
C. Deakin ◽  
G. Littlejohn ◽  
H. Griffiths ◽  
T. Smith ◽  
C. Osullivan ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Data ◽  
Real World ◽  
Rank Test ◽  
P Value ◽  
Continuous Variables ◽  
Linear Quadratic ◽  
First Line ◽  
Modest Improvement ◽  
Over Time

Background:The availability of biosimilars as non-proprietary versions of established biologic disease-modifying anti-rheumatic drugs (bDMARDs) is enabling greater access for patients with rheumatic diseases to effective medications at a lower cost. Since April 2017 both the originator and a biosimilar for etanercept (trade names Enbrel and Brenzys, respectively) have been available for use in Australia.Objectives:[1]To model effectiveness of etanercept originator or biosimilar in reducing Disease Activity Score 28-joint count C reactive protein (DAS28CRP) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) treated with either drug as first-line bDMARD[2]To describe persistence on etanercept originator or biosimilar as first-line bDMARD in patients with RA, PsA or ASMethods:Clinical data were obtained from the Optimising Patient outcomes in Australian rheumatoLogy (OPAL) dataset, derived from electronic medical records. Eligible patients with RA, PsA or AS who initiated etanercept originator (n=856) or biosimilar (n=477) as first-line bDMARD between 1 April 2017 and 31 December 2020 were identified. Propensity score matching was performed to select patients on originator (n=230) or biosimilar (n=136) with similar characteristics in terms of diagnosis, disease duration, joint count, age, sex and concomitant medications. Data on clinical outcomes were recorded at 3 months after baseline, and then at 6-monthly intervals. Outcomes data that were missing at a recorded visit were imputed.Effectiveness of the originator, relative to the biosimilar, for reducing DAS28CRP over time was modelled in the matched population using linear mixed models with both random intercepts and slopes to allow for individual heterogeneity, and weighting of individuals by inverse probability of treatment weights to ensure comparability between treatment groups. Time was modelled as a combination of linear, quadratic and cubic continuous variables.Persistence on the originator or biosimilar was analysed using survival analysis (log-rank test).Results:Reduction in DAS28CRP was associated with both time and etanercept originator treatment (Table 1). The conditional R-squared for the model was 0.31. The average predicted DAS28CRP at baseline, 3 months, 6 months, 9 months and 12 months were 4.0 and 4.4, 3.1 and 3.4, 2.6 and 2.8, 2.3 and 2.6, and 2.2 and 2.4 for the originator and biosimilar, respectively, indicating a clinically meaningful effect of time for patients on either drug and an additional modest improvement for patients on the originator.Median time to 50% of patients stopping treatment was 25.5 months for the originator and 24.1 months for the biosimilar (p=0.53). An adverse event was the reason for discontinuing treatment in 33 patients (14.5%) on the originator and 18 patients (12.9%) on the biosimilar.Conclusion:Analysis using a large national real-world dataset showed treatment with either the etanercept originator or the biosimilar was associated with a reduction in DAS28CRP over time, with the originator being associated with a further modest reduction in DAS28CRP that was not clinically significant. Persistence on treatment was not different between the two drugs.Table 1.Respondent characteristics.Fixed EffectEstimate95% Confidence Intervalp-valueTime (linear)0.900.89, 0.911.5e-63Time (quadratic)1.011.00, 1.011.3e-33Time (cubic)1.001.00, 1.007.1e-23Originator0.910.86, 0.960.0013Acknowledgements:The authors acknowledge the members of OPAL Rheumatology Ltd and their patients for providing clinical data for this study, and Software4Specialists Pty Ltd for providing the Audit4 platform.Supported in part by a research grant from Investigator-Initiated Studies Program of Merck & Co Inc, Kenilworth, NJ, USA. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck & Co Inc, Kenilworth, NJ, USA.Disclosure of Interests:Claire Deakin: None declared, Geoff Littlejohn Consultant of: Over the last 5 years Geoffrey Littlejohn has received educational grants and consulting fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Novartis, Pfizer, Janssen, Sandoz, Sanofi and Seqirus., Hedley Griffiths Consultant of: AbbVie, Gilead, Novartis and Lilly., Tegan Smith: None declared, Catherine OSullivan: None declared, Paul Bird Speakers bureau: Eli Lilly, abbvie, pfizer, BMS, UCB, Gilead, Novartis

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