Biosimilar Agents Research Articles

Medicare reimbursement trends of biological reference agents and their biosimilars.

11155 Background: Biosimilars have the potential to reduce healthcare costs for payers and provide savings to patients by introducing competition and driving down prices. Centers for Medicare and Medicaid Services’ (CMS) Average Sales Price (ASP) is used as an index price to determine Medicare drug reimbursement (MCR) in the United States and is published on a quarterly basis. We studied the trends of ASP and MCR reimbursement rates for reference and biosimilar agents. Methods: Using publicly available quarterly CMS data, we evaluated and compared the trends of MCR for 7 reference and 25 biosimilar agents for a period of 2 years before and 5 years after launch. We evaluated the MCR for filgrastim, pegfilgrastim, bevacizumab, trastuzumab, rituximab, infliximab, epoetin-alfa, and their respective biosimilars. Results: On average, the published MCR for all reference agents increased by 9.2% (range: 0.6% to 16.8%) over the 2-year period prior to the biosimilar launch. Over the 5-year period following the launch of the first biosimilar, reference agents’ MCR fell 32.7% (range: -8.0% to -78.0%) while biosimilar agents’ MCR fell 50.3% (range: -3.7% to -90.5%) over the same period, with a median follow-up period of 16 quarters. Biosimilar MCR rates fell at an accelerated rate compared to reference agents. 76% (19 of 25) of the biosimilars that entered the market had an initial MCR below, and 20% (5 of 25) above, that of the reference agent. 16 of 18 successive biosimilars for reference agents launched with a MCR above that of the first biosimilar. Despite the fall in MCR, reference agents’ rates in the most recent quarter were 2x higher than their corresponding biosimilar agents, except for pegfilgrastim, which had a precipitous fall in MCR (87%) after biosimilar launch to a price lower than 5 of its 6 biosimilars. Conclusions: Biosimilars, with lower Medicare reimbursement at launch, and an accelerated decline in ASP post-launch, deliver on the goal of driving lower healthcare costs and increased savings. Biosimilar competition breaks the price increase trends with reference agents and contributes to a decrease in reference agent drug reimbursement. The effects of manufacturer rebates, payer policies, 340b programs, and discounts on ASP and Medicare reimbursement are also areas of active investigation.

Real-world evaluation of oncolytic biosimilar adoption on medication adherence and out-of-pocket costs among members of a national payor.

e23092 Background: Biosimilars provide quality, safe, effective, and lower-cost alternative treatment options that have no difference from their reference product. CVS Health® recently launched a biosimilar adoption strategy to expand access to biosimilars and drive sustainable cost savings and options for consumers. The purpose of this study is to compare treatment duration, adherence, and out-of-pocket (OOP) costs between individuals receiving oncology biosimilars versus oncology reference branded products. Methods: This retrospective cohort study included adult commercial fully insured and Medicare members of a large national payor with ≥1 claim for a physician-administered oncology biosimilar or reference branded product between 12/01/2020 and 11/30/2022. To assess adherence, we compared claims per month, defined as the total claims during the study divided by the number of months patients received medication and time on therapy, defined as the number of months between first claim in period and last claim in period (inclusive). OOP costs, defined as the sum of deductible and applicable coinsurance at the time of visit, were examined as a secondary endpoint. Continuous variables were compared with Student’s t-test; categorical variables were compared with a Chi-squared test. P values < 0.05 were considered significant. Results: 2,597 individuals were included in the evaluation with between-group differences in age, gender, and agent received (all p < 0.001). 41,182 claims were evaluated; 59.2% were for reference branded products. 3,817 medication combinations were evaluated; 64.2% received a reference branded product. Individuals receiving biosimilar agents had more total claims (mean [standard deviation, SD]: 13.9 [6.3] vs. 13.1 [7.5]; p = 0.003) and claims per month (1.4 [0.5] vs. 1.3 [0.6]; p < 0.001). However, individuals receiving reference branded products had longer time on therapy (10.5 [4.1] vs. 10.0 [3.7] wk; p = 0.006). When examining oncology agents only (n = 1,992), individuals receiving biosimilar agents had more claims per month (1.4 [0.5] vs. 1.3 [0.6]; p < 0.001). In contrast, individuals receiving reference branded products had longer time on therapy (11.0 [4.1] vs. 10.1 [3.7] wk; p < 0.001). Individuals prescribed oncology support reference branded products and oncology treatment reference branded products experienced 475% and 350% higher OOP spend compared to individuals prescribed biosimilars (both p < 0.001), respectively. Conclusions: This real-world evaluation leveraging administrative claims revealed that individuals receiving oncology biosimilars appear to experience shorter observed time on therapy, higher adherence, and lower OOP spend than individuals receiving reference branded products. Despite superior member-centric outcomes, reference branded products were prescribed more often than biosimilars.

P1002 De novo and drug-induced skin manifestations in Inflammatory Bowel Disease patients: The impact of anti-tumour necrosis factor therapy

Abstract Background Skin disorders in inflammatory bowel disease (IBD) consist of extra-intestinal manifestations (EIM) or drug-induced lesions. This study explores de novo skin lesions and the emergence of immune-mediated skin disorders induced by anti-tumour necrosis factor (anti-TNF) agents. Methods Patients with EIMs, de novo skin lesions, and drug-induced skin eruptions were identified from an IBD patient database on advanced therapies. Data on time intervals from the initiation of IBD treatment to the development of skin disorders, causative agents, and subsequent management were collected. Results In a cohort of 1,773 patients (993 with ulcerative colitis, 746 with Crohn’s disease, and 31 with IBD unclassified), 30% (549) exhibited skin manifestations, with 28% (491 cases) showing de novo skin conditions. Identified skin manifestations included psoriasis/psoriasiform rash (18.3%), eczema (16.3%), seborrheic dermatosis (13.8%), acne (9.8%), actinic keratosis (5.3%), rosacea (4.7%), erythema nodosum (EN, 3.5%), cutaneous Crohn's disease (CCD, 2.6%), folliculitis (1.8%), pyoderma gangrenosum (PG, 1.5%), and others. Of the skin lesions, 31.8% (175) occurred before the IBD diagnosis, with a median duration of 8 years, while 51.9% (286) developed post-diagnosis unrelated to therapies. Biologic therapies improved extraintestinal skin lesions in 19 patients (3.4%). Notably, all 3 EN cases and 4 out of 5 PG cases achieved full resolution with biological treatments, leading to improved IBD activity. Similarly, 9 out of 10 Crohn’s disease patients with CCD showed improved skin conditions following biological treatments Fifty-eight patients (3.3%) experienced drug-induced skin lesions, with a median age at IBD diagnosis of 35 years (ranging from 17 to 67). The majority (91.3%) of cases were attributed to anti-TNF agents, and psoriasiform lesions were the most prevalent (60.3%). The median duration from treatment initiation to the onset of drug-induced skin lesions was 23 months (ranging from 0 to 115 months). Among the affected individuals, 19 using originator anti-TNF agents developed skin lesions, with 13 having psoriatic lesions. In comparison, 34 patients on biosimilar anti-TNF agents developed skin lesions, and 23 of them had psoriatic lesions. The progression of skin lesions led to anti-TNF discontinuation in 33 patients, of whom 25 transitioned to Vedolizumab or Ustekinumab. Resolution occurred in 22 patients. Conclusion Anti-TNF-induced skin lesions, notably psoriasiform lesions, appear to be more prevalent in the biosimilar era among IBD patients, often leading to discontinuation. Nevertheless, resolution is possible through strategic switches to alternative biologic agents.

Effectiveness and Safety of Biosimilars in Pediatric Non-infectious Uveitis: Real-Life Data from the International AIDA Network Uveitis Registry.

Since many biological drug patents have expired, biosimilar agents (BIOs) have been developed; however, there are still some reservations in their use, especially in childhood. The aim of the current study is to evaluate the efficacy and safety of tumor necrosis factor (TNF) inhibitors BIOs as treatment for pediatric non-infectious uveitis (NIU). Data from pediatric patients with NIU treated with TNF inhibitors BIOs were drawn from the international AutoInflammatory Disease Alliance (AIDA) registries dedicated to uveitis and Behçet's disease. The effectiveness and safety of BIOs were assessed in terms of frequency of relapses, risk for developing ocular flares, best-corrected visual acuity (BCVA), glucocorticoids (GCs)-sparing effect, drug survival, frequency of ocular complications, and adverse drug event (AE). Forty-seven patients (77 affected eyes) were enrolled. The BIOs employed were adalimumab (ADA) (89.4%), etanercept (ETA) (5.3%), and infliximab (IFX) (5.3%). The number of relapses 12months prior to BIOs and at last follow-up was 282.14 and 52.43 per 100 patients/year. The relative risk of developing ocular flares before BIOs introduction compared to the period following the start of BIOs was 4.49 (95% confidence interval [CI] 3.38-5.98, p = 0.004). The number needed to treat (NNT) for ocular flares was 3.53. Median BCVA was maintained during the whole BIOs treatment (p = 0.92). A significant GCs-sparing effect was observed throughout the treatment period (p = 0.002). The estimated drug retention rate (DRR) at 12-, 24-, and 36-month follow-up were 92.7, 83.3, and 70.8%, respectively. The risk rate for developing structural ocular complications was 89.9/100 patients/year before starting BIOs and 12.7/100 patients/year during BIOs treatment, with a risk ratio of new ocular complications without BIOs of 7.1 (CI 3.4-14.9, p = 0.0003). Three minor AEs were reported. TNF inhibitors BIOs are effective in reducing the number of ocular uveitis relapses, preserving visual acuity, allowing a significant GCs-sparing effect, and preventing structural ocular complications. ClinicalTrials.gov ID NCT05200715.

Outcomes of the use of infliximab biosimilars in rheumatology and gastroenterology clinics.

The originator infliximab product, Remicade, was approved by the US Food and Drug Administration in August 1998 for the management of Chron's disease. Since this time, several infliximab biosimilar agents have entered the market to introduce competition and lower costs for patients as well as health care systems. Clinical trials comparing infliximab biosimilars with the originator product have consistently demonstrated noninferiority, along with similar adverse effect profiles, leading to the approval of 3 additional biosimilars: Renflexis (infliximab-abda), Avsola (infliximab-axxq), and Inflectra (infliximab-dyyb). In 2021, the University of North Carolina rheumatology and gastroenterology outpatient clinics began an initiative to convert patients from the originator infliximab product to biosimilar agents Renflexis or Avsola based on market costs. Subsequently, a retrospective evaluation was conducted to analyze the clinical outcomes of patients that were switched to a biosimilar agent compared with those that were only ever using either the originator or biosimilar agent. A total of 180 patients were analyzed, of which half were prescribed a biosimilar as a result of the conversion initiative. Of these 90 patients, 79 (87.8%) were maintained on a single biosimilar agent without requiring a switch to an alternative infliximab product. We conclude that the effort to convert clinically stable patients to a biosimilar product resulted in a significant increase in biosimilar use within the health system. This is thought to have resulted in significant financial advantages both to our institution as well as patients, without sacrificing overall clinical control.

Transforming Drug Design: Innovations in Computer-Aided Discovery for Biosimilar Agents

In pharmaceutical research and development, pursuing novel therapeutics and optimizing existing drugs have been revolutionized by the fusion of cutting-edge technologies and computational methodologies. Over the past few decades, the field of drug design has undergone a remarkable transformation, catalyzed by the rapid advancement of computer-aided discovery techniques and the emergence of biosimilar agents. This dynamic interplay between scientific innovation and technological prowess has expedited the drug discovery process and paved the way for more targeted, effective, and personalized treatment approaches. This review investigates the transformative computer-aided discovery techniques for biosimilar agents in reshaping drug design. It examines how computational methods expedite drug candidate identification and explores the rise of cost-effective biosimilars as alternatives to biologics. Through this analysis, this study highlights the potential of these innovations to enhance the efficiency and accessibility of pharmaceutical development. It represents a pioneering effort to examine how computer-aided discovery is revolutionizing biosimilar agent development, exploring its applications, challenges, and prospects.

Similar Growth Outcomes in Children with Inflammatory Bowel Disease Initiated on Infliximab Originator or Biosimilar.

Growth is an important clinical outcome, especially in childhood-onset inflammatory bowel disease (IBD). Prior research has demonstrated growth improvements with infliximab therapy. There are limited studies evaluating whether clinical and growth outcomes in children initiated on the infliximab originator and infliximab biosimilar are similar. This was a single-center retrospective review of patients with IBD, younger than 17 years old, and initiated on the infliximab originator or biosimilar for at least 12 months between April 2016 and February 2021. Propensity score matching was utilized. Laboratory values, disease activity scores, and growth values were collected at baseline (prior to infliximab initiation), 6 months, and 12 months post initiation. Linear mixed models with random intercepts were used to test differences in measures over time and between study groups. There were 113 patients on the originator and 39 patients on a biosimilar who met eligibility criteria. Propensity score methodology identified 37 dyads (1:1 match). Weight, height, and body mass index z scores increased over time (from baseline to 12 months) for both groups ( P < 0.05) and there was a similar rate of change between study groups. Clinical outcomes of lab values (albumin, C-reactive protein, and hemoglobin) and disease activity scoring were similar from baseline to 12 months between study groups. There were similar improvements in growth and clinical outcomes in patients initiated on the infliximab originator compared to an infliximab biosimilar agent. This study adds to the limited research evaluating whether infliximab biosimilars have similar growth outcomes in children with IBD.

Safety and efficacy of ranibizumab biosimilar (Razumab®) as a cost-effective alternative to the innovator molecule for macular disorders in real-world

: To report the clinical efficacy and safety of the intravitreal ranibizumab biosimilar molecule, Razumab® (IVRz) as an economic alternative to the innovator molecule (Lucentis) in macular diseases under real-world conditions.: A single‑ center, prospective study of 100 consecutive eyes undergoing three-monthly IVRz between April 2020 to March 2021 for a variety of macular disorders including diabetic macular edema (DME), neovascular age‑related macular degeneration (nAMD), retinal vein occlusion (RVO), and myopic choroidal neovascular membrane (mCNVM). The main outcome measures were changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), intraretinal-fluid (IRF), and subretinal-fluid (SRF) along with a safety analysis at weeks 4, 8, and 12 respectively. : Of the 100 eyes of 100 patients undergoing IVRz, a majority had DME (39 eyes; 39%) followed by RVO (34 eyes; 34%), nAMD (21 eyes; 21%), and mCNVM (6 eyes; 6%). Mean BCVA improved from baseline to weeks 4, 8, and 12 (P&amp;#60;0.001). A significant reduction in CST from the baseline was also noted at all the visits (P&amp;#60;0.001). On qualitative analysis, resolution of SRF and IRF was observed in 61.47% and 61.71% of eyes respectively. No serious ocular or systemic adverse events were noted.: Our real-world data suggests that IVRz therapy is safe and efficacious for the management of varied macular pathologies. The cost-effectiveness and systemic and ocular safety of this regulatory-approved biosimilar makes it a suitable alternative to the branded drug. Further comparative studies into the benefit-cost analysis of these biosimilar and branded agents are warranted to better understand the health economics of anti-vascular endothelial growth factor (anti-VEGF) therapy in chorioretinal disorders.

An assessment of the provider financial risk impacts of adoption of biosimilars in the Medicare Oncology Care Model.

6613 Background: In 2016, Medicare launched the Oncology Care Model (OCM)—a Value-Based Payment (VBP) initiative providing per-beneficiary prospective payment to providers, and performance-based financial incentives/risks based on cost of care in 6-month ‘episodes’ vs. risk-adjusted benchmarks for cancer patients receiving chemotherapy. Oncology biosimilars may play an important role in managing financial risk in the OCM and other VBP models, but the real-world impact remains uncertain. The objective of this study was to quantify the impact of biosimilar adoption on oncology provider financial risk under the OCM using real-world data. Methods: We estimated the impact of biosimilar adoption on provider financial risk from 2019 to 2021 by modeling the methods (episode framing, pricing, &amp; risk adjustment) of the OCM. Cancer episodes were identified from the 5% Medicare Limited Data Set (LDS). The study sample consisted of cancer treatment episodes with use of any of the following agents or their biosimilars: bevacizumab, rituximab, trastuzumab, epoetin alfa, filgrastim, and pegfilgrastim. Financial risk was defined as the difference in observed total cost of care vs. OCM target episode cost. The primary outcome was the difference in financial risk (expressed in nominal $USD) under observed use of reference and/or biosimilars vs. hypothetical use of 100% reference agent. Results: The study sample included 8851 6-month episodes initiating between 1/2019 and 6/2021. Biosimilar adoption resulted in a mean cost reduction of $1,020 per episode vs. hypothetical 100% use of reference agents. Biosimilar use increased markedly over the study horizon--with 24% of episodes with a biosimilar in Half (H)1 2019, increasing to 65% by H1 2021, and driven by increased use of antineoplastic (1% to 36%) vs. supportive care biosimilar agents (23% to 34%). Mean financial risk reduction grew with the rapid adoption of biosimilars over this period. The average risk reduction in episodes initiating in H1 2021 was about 10 times larger than that seen in episodes initiating in the H1 2019 ($2060 vs $201, See Table). Observed mean cost was below the OCM target cost ($48808) in H1 2021 but exceeded the target cost in all other periods (range: +$1451 to +$4966). Conclusions: From 2019 to 2021, rapid adoption of biosimilars in Medicare fee-for-service beneficiaries included in the LDS led to substantial cost savings and reduction in risk for cancer episodes evaluated under the OCM methods. Broad adoption of biosimilars is a key strategy that providers in oncology VBP models will need to consider to manage financial risk. [Table: see text]

E011 What information should we provide to inform and empower our patients to participate in shared decision making? The patient perspective

Abstract Background/Aims With an increasing number of biologic and targeted synthetic disease-modifying anti-rheumatic drugs and their biosimilar agents coming to the market, there is an increased choice of treatments available to patients. It is paramount to understand what information patients require to weigh up risks and benefits of each treatment to empower them to take part in shared decision making. This study aims to explore which factors (in addition to their clinical history) are deemed most important by patients when choosing a treatment and if they believe cost of treatment should be considered. Methods 74 randomly selected patients, who had been referred to the biologic or targeted synthetic treatment pathway, were invited to complete an anonymous online survey. Paper responses were also offered to patients who were unable to participate electronically, to avoid digital exclusivity. The survey consisted of 10 questions looking at patient perspectives questioning if they wanted to be involved in decisions about biologic and targeted synthetic treatment, which patient factors were important to them, if they considered cost as an important factor, if they would find a decision aid such as graphic/diagrams useful and if they would like a written record of how a shared decision was made. Results A total of 50 patients responded to the survey (40/50 online vs. 10/50 paper survey). 94% of patients stated that they would like to be involved in decisions about choice of biologic/ targeted synthetic medication. 58% said they think it is important to consider the cost of treatment. Based on the responses from the patients, the top patient factors (chosen by more than 60% of respondents) which were considered important are: how treatment is given, where treatment is given, how often it needs to be taken, how frequently monitoring is required, likelihood and severity of possible side effects. 66% of respondents said they would like to be shown a graphic/diagram to support their shared decision making and 80% of respondents said they would like a written record to explain how a shared decision was made about the best treatment for them. Conclusion The majority of patients included in our study would like to be actively involved in the shared decision-making process and would like to be given information such as route, frequency and location of administration, frequency of monitoring and severity and likelihood of side effects. The majority felt they would benefit from having a graphic/ diagram with all the relevant information summarised to help understand information easily. Providing a written record of the shared decision making will also make the process more transparent. Feedback from the survey has informed our service redesign, specifically our approach to shared decision making, to improve our patients’ experience. Disclosure N. Mathews: None. F. Ferris: None. A. Bayliss: None. E. McCormack: None. K. Summerhayes: None. H. De Vere: None. E. Rose-Parfitt: None.

Adalimumab originator versus adalimumab biosimilars in inflammatory bowel disease in Australia

ABSTRACT Background Biosimilar adalimumabs have improved treatment access, but without any clinical advantage, distributors rely on delivery device design-enhancements, support services, and removal of painful excipients to capture market share. Prescribers, however, are often unaware of these differences. This article compares and contrasts originator versus biosimilar adalimumab agents to identify key differences that might influence adalimumab selection. Research design and methods We reviewed listed adalimumab biosimilars in Australia and compared them to the originator adalimumab. Similarities and differences identified were confirmed with the manufacturers via two rounds of interviews: the first to collate a list of features and benefits of their product, and the second to consolidate and confirm the data. Results The originator adalimumab Humira [by AbbVie, U.S.A] and four adalimumab biosimilars (Amgevita [by Amgen, U.S.A], Hadlima [by Organon, U.S.A], Hyrimoz [by Sandoz, Switzerland], and Idacio [by Fresenius Kabi, Germany]) are included in this review. Key differences identified include product formulation, dosages available, delivery devices, physician support, patient support, and the supply of other biosimilar products by the company. Conclusion Adalimumab biosimilars are different from each other with unique advantages and disadvantages likely to influence prescriber and patients. Therefore, the choice of agent should be individualized to the needs of the patient and the healthcare service.

A175 REAL-WORLD EXPERIENCE ON SWITCHING FROM ADALIMUMAB TO BIOSIMILARS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE – AN OBSERVATIONAL STUDY FROM THREE TERTIARY CARE CENTRES

Abstract Background Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the bowel which includes ulcerative colitis (UC), Crohn’s disease (CD) or unspecific IBD (IBDu). Adalimumab (ADA), a humanized monoclonal IgG antibody against tumour necrosis factor-alpha (TNFa), is an effective treatment for IBD. HumiraTM is an anti-TNFa agent that was approved by Health Canada for the treatment of IBD. In May of 2019, the British Columbia government pharmaceutical benefit plan implemented a biosimilar initiative in May 2019, mandating a non-medical switch from HumiraTM to one of the biosimilar drugs. Purpose We aimed to evaluate the real-world experience on the comparative safety and effectiveness of adalimumab biosimilar therapy after a mandatory, non-medical switch. Method We performed a retrospective chart review of all patients with IBD who either remained on HumiraTM or were switched to an adalimumab biosimilar agent, Idacio, at three tertiary care centres. Patients’ demographic data, disease status including CRP and fecal calprotectin before and after switch, and hospital visits or admission after switch were collected. Statistical analysis was performed using ANOVA and t-test. Result(s) Of the 191 patients included in the study, 145 patients underwent the provincial mandated switch from HumiraTM to a biosimilar agent, Idacio® , whereas 46 patients remained on HumiraTM. The median age at IBD diagnosis was 27 years (range 3-76 years), and at biosimilar switch was 43.5 years (15-78 years). Median disease duration prior to biosimilar switch was 13.5 years (range 0-69 years). 55.1% of patients were male, and 12.9% of patients were active smokers. CD was found in 78.9% of patients, and 19.9% of patients had UC. After biosimilar switch, adverse events, such as rash, nausea, or vomiting, were noted in 10 patients in the biosimilar group, and 7 patients required switch back to HumiraTM. All patients in the HumiraTM group stayed on that therapy. One patient stopped the biosimilar agent due to development of a new cancer requiring chemotherapy. None of the patients required IBD-related emergency department visit or hospital admission. Additionally, there was no difference in CRP or fecal calprotectin values measured before and after the biosimilar switch, and when compared to the patients who stayed on HumiraTM (p=0.48, and p=0.142, respectively). Conclusion(s) We conclude that the clinical benefit of HumiraTM was sustained after a non-medical switch to an adalimumab biosimilar. There was no risk of relapse, emergency visit, or hospital admission seen in this study. This is the first Canadian study to establish the safety and efficacy of switch to non-medical switch to an adalimumab biosimilar agent. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Biosimilars for retinal diseases: United States-Europe awareness survey (Bio-USER – survey)

ABSTRACT Purpose To assess the awareness of biosimilar intravitreal anti-VEGF agents among retina specialists practicing in the United States (US) and Europe. Methods A 16-question online survey was created in English and distributed between Dec 01, 2021 and Jan 31, 2022. A total of 112 respondents (retinal physicians) from the US and Europe participated. Results The majority of the physicians (56.3%) were familiar with anti-VEGF biosimilars. A significant number of physicians needed more information (18.75%) and real world data (25%) before switching to a biosimilar. About one half of the physicians were concerned about biosimilar safety (50%), efficacy (58.9 %), immunogenicity (50%), and their efficacy with extrapolated indications (67.8 %). Retinal physicians from the US were less inclined to shift from off-label bevacizumab to biosimilar ranibizumab or on-label bevacizumab (if approved) compared to physicians from Europe (p=0.0001). Furthermore, physicians from the US were more concerned about biosimilar safety (p=0.0371) and efficacy compared to Europe (p= 0.0078). Conclusions The Bio-USER survey revealed that while the majority of retinal physicians need additional information regarding the safety, efficacy and immunogenicity when making clinical decisions regarding their use. Retinal physicians from US are more comfortable in continuing to use off-label bevacizumab compared to physicians from Europe.

Clinical Efficacy of Biosimilar Switch of Adalimumab for Management of Uveitis

ABSTRACT Background Adalimumab has demonstrated efficacy in non-infectious uveitis. With the introduction of biosimilar agents such as Amgevita, we aimed to quantify efficacy and tolerability compared to Humira in a multi-centre UK cohort Methods Patients identified from tertiary uveitis clinics in 3 centres, after institution-mandated switching was implemented. Results Data collected for 102 patients, aged 2–75 years, with 185 active eyes. Following switch, rates of uveitis flare were not significantly different (13 events before, 21 after, p = .132). Rates of elevated intraocular pressure were decreased (32 before, 25 afterwards, p = .006) and dosing of oral and intra-ocular steroids was stable. Twenty-four patients (24%) requested to return to Humira, commonly due to pain from injection or technical difficulty with the device. Conclusion Amgevita is safe and effective for inflammatory uveitis with non-inferiority to Humira. Significant numbers of patients requested to switch back due to side effects including injection site reactions.

Biosimilars for Pediatric Patients With Inflammatory Bowel Disease: Pediatric Gastroenterology Clinical Practice Survey.

Biosimilars are biological agents that have been demonstrated to have similar safety and efficacy profiles as the originator. The objective of this study was to evaluate the perspectives of pediatric gastroenterologists in the United States (U.S.) toward biosimilar use and to explore factors that impact their comfort level with prescribing infliximab biosimilars. A cross-sectional survey was developed and distributed to pediatric gastroenterology physicians from the U.S. via a listserv (Pediatric gastroenterology Bulletin Board). Respondent's demographics were recorded. Using a 6-point Likert scale, the survey assessed the respondent's perceptions toward biosimilars and initiating switches from the originator to biosimilar agent along with factors impacting provider's comfort level. Fischer exact tests were used to detect statistically significant differences in responses for hypotheses of interest. One hundred thirty-nine pediatric gastroenterologists completed the online survey (response rate 5.4%). Eighty-seven percent of respondents reported being comfortable prescribing infliximab biosimilars to anti-tumor necrosis factor naive patients, and 69% reported being comfortable doing a one-time switch if the patient was in clinical remission. Factors that negatively impacted a respondent's comfort level included respondents not practicing at an ImproveCareNow (ICN) center and managing less than 50 patients with inflammatory bowel diseases (IBD). Nearly 90% of pediatric gastroenterologists felt comfortable prescribing an infliximab biosimilar, and 70% felt comfortable with a one-time switch to the biosimilar if the patient was in clinical remission. Involvement in ICN a learning health system and caring for higher numbers of patients with IBD was associated with increased provider comfort with biosimilar use.

P487 Anti TNF induced psoariasiform skin eruptions are increasing in in the biosimilar era – a descriptive study of drug induced skin manifestations and their management

Abstract Background Skin disorders as extra-intestinal manifestations of inflammatory bowel disease 9IBD) are well recognized. In addition, contribution of drugs used in IBD in development of skin cancers is now fully understood. However, there are increasing reports of drug induced immune skin disorders resulting from or contributed by anti TNF agents. We aim to describe the etiology, manifestations and therapeutic approaches of anti TNF induced skin eruptions from a large tertiary center cohort. Methods A prospective database of IBD patients receiving biologics for IBD was interrogated for those who developed skin eruptions following initiation of anti-TNF therapy. We excluded patients who had pre-existing skin manifestations. All patients had dermatological expert review and confirmation of diagnosis as drug induced skin disorder. We collected their disease characteristics, time interval from initiation of biologics to development of skin disorder, the putative causative agent and the treatment of the skin lesions Results Sixty-eight patients (median age= 30 years, Female 44, male 24) among 1478 patients who received at least one dose of biologics developed a drug induced immune skin disorder. Median duration to development of skin lesions was 7.5 months. Anti TNF agents were responsible for 88.5% of the skin lesions with the commonest lesions being psoriasiform lesions in 34 (50%) patients. In our cohort, the psoriasiform lesions were more prevalent in patients who used biosimilar anti-TNF agents compared to the originator agent (31 vs 3). Forty patients required cessation of anti TNF agents because of skin eruptions. Twenty-eight of these were switched to ustekinumab with resolution of skin eruptions in 27 patients. Conclusion Anti TNF induced psoariasiform skin lesions appear to be more prevalent in the biosimilar era. Half of these patients will need treatment switch; ustekinumab appears to be an effective option in these patients

DOP55 The increasing burden of direct and indirect costs of IBD

Abstract Background The cost of care for inflammatory bowel disease (IBD) has nearly doubled over the last two decades. With an increasing number of patients and evolving treatment paradigms utilizing costly but efficacious biologic agents earlier and more often, the cost burden is only expected to worsen. Furthermore, IBD carries significant indirect costs to lost productivity of patients and their caregivers and out-of-pocket healthcare expenses borne directly by patients. Methods This talk will explore the current landscape and drivers of IBD direct costs and indirect costs as well as discuss challenges in assessing and comparing such data across countries Results Direct costs of IBD management have shifted substantially in recent years, primarily due to the emergence and penetrance of biologic therapy into clinical practice. Despite the increased use of biologic agents in IBD treatment, the expenditure on hospitalization and surgery has had a relatively small impact on reductions in cost, and the mean per capita costs spent on biologics in recent years is higher than what was saved on hospitalization per capita. In fact, direct health care costs associated with IBD treatment have dramatically increased over the last decade. New biologics and small molecules are also expected to be approved in the coming years, which is only likely to further increase the economic burden of IBD. These drivers of increasing costs may be offset by the recent loss of patent exclusivity for infliximab and adalimumab in much of the Western world, which has allowed for increased competition in the form of biosimilar agents and a reduction in prices. The greatest burden of indirect costs in this population relates to absenteeism and presenteeism among working individuals and premature retirement. However, costs related to reduced professional development and personal achievement due to illness—as well as caregiver costs—are largely unknown. Conclusion IBD is an expensive chronic disease with payments only expected to rise. Treating CD remains more expensive than treating UC and biologics escalate treatment costs and these are not offset by possible reductions of hospitalization and other costs. Direct costs differ substantially between countries and health care systems. Indirect cost constitute a significant burden on society

GROWTH OUTCOMES OF IV ANTI-TNF BIOSIMILARS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Biosimilars are biologic products similar in safety and efficacy to the originator product. Tumor necrosis factor-alpha inhibitors (anti-TNFs) are used in the treatment of inflammatory bowel diseases (IBD). There are limited studies evaluating the long-term outcomes of anti-TNF biosimilars in children with IBD. Growth is an important clinical outcome, especially in childhood-onset IBD. However, no study to date has compared growth outcomes in patients initiated on the IV anti-TNF originator as compared to a biosimilar. METHODS This was a single-center retrospective review of patients with IBD, younger than 16 years old, and initiated on the IV anti-TNF originator or a biosimilar between April 2016 and February 2021 at Nationwide Children’s Hospital. To be eligible for the study and evaluate the primary outcome, patients must remain on the IV anti-TNF therapy for at least 12-months. We used propensity score methodology to identify 37 pairs of matched patients based on baseline characteristics (age of anti-TNF initiation, disease (CD vs UC/IC), behavior, location, perianal type, race). Demographic data, laboratory values, disease activity scores, and growth values (z-scores were recorded for weight, height, and BMI) were collected at baseline (prior to anti-TNF initiation) and 6-months and 12-months post initiation. Linear mixed models with random intercepts accounting for within patient correlation of measurements were fit to test differences in measures over time and between study groups. Hypothesis testing was conducted at an alpha of 0.05 to be used for all statistical analyses. RESULTS There were 113 patients on the originator and 39 patients on a biosimilar who met our eligibility criteria. Nineteen percent of patients on the originator and 16% of patients on a biosimilar were excluded from analysis due to discontinuing the IV anti-TNF agent prior to 12 months. Weight, height, and BMI z-scores increased over time (from baseline to 12-months) for both groups (p&amp;lt;0.05). There was not a significant difference in the rate of change for weight, height, or BMI z-scores between study groups. Clinical outcomes of lab values (albumin, c-reactive protein, and hemoglobin) were not statistically different in the rate of change from baseline to 12-months between patients initiated on the originator or biosimilar. There also was not a significant difference in the pediatric Crohn’s disease activity index, pediatric ulcerative colitis activity index, or the physician global assessment between patients initiated on the biosimilar or originator from baseline to 12-months. CONCLUSIONS There were similar improvements in growth and clinical outcomes in patients initiated on the IV anti-TNF originator compared to a biosimilar agent. This is the first study to evaluate whether anti-TNF biosimilars have similar growth outcomes in children with IBD.

ABRAXANE DESENSITIZATION

<h3>Introduction</h3> Adverse and hypersensitivity reactions to Taxol chemotherapy are not uncommon. The Cremophor solvent used in Taxol formulations has been associated with adverse infusion and delayed reactions. A biosimilar agent, Abraxane, which uses an albumin solvent, is often better tolerated. We present a case of severe hypersensitivity to Taxol and a unique protocol for Abraxane desensitization. <h3>Case Description</h3> A 38-year-old female with endometrial cancer presented with rash and lip swelling seven days after her first Carboplatin and Paclitaxel (Taxol) doses. She tolerated a Carboplatin challenge ruling out Carboplatin as the culprit. While undergoing a Paclitaxel challenge, she experience an anaphylactic reaction requiring intubation and epinephrine infusion. Given the severity of her reaction, there was concern that patient had reacted to Paclitaxel and not the solvent alone. Thus, her treatment plan was switched to Abraxane with plan to desensitize patient first. Desensitization to Abraxane was complicated by lack of medication stability once mixed and risk of medication dissociation with dilution. A unique 1 bag desensitization protocol was created. During Abraxane desensitization, patient had a hypersensitivity reaction which was treated with Benadryl and Methylprednisolone. Patient tolerated the remainder of the Abraxane desensitization. <h3>Discussion</h3> We report a challenging case of a patient with both immediate and delayed hypersensitivity reactions to Paclitaxel, who was able to undergo successful desensitization to Abraxane through a unique 1 bag protocol despite limitations of medication stability and dilution capabilities. Furthermore, patient's IgE-mediated reactions to both Paclitaxel and Abraxane further demonstrate that she is indeed allergic to the active ingredient and not the solvent.

Biosimilars for immune-mediated inflammatory diseases: a managed care perspective

Biosimilars hold the promise of substantial potential cost savings in health care with no compromise in the efficacy and safety of treatment. Despite this, their adoption in the United States has been substantially slower than might have been expected. In addition to patient and provider barriers to their widespread adoption as discussed in the second article in this supplement, additional potential barriers to their use are inherent to the current US health care system. In this article, we examine biosimilar agents from a managed care perspective and discuss some of the reasons behind their delayed adoption in the United States.