Adalimumab Research Articles

Dynamic changes in the gut microbiota composition during adalimumab therapy in patients with ulcerative colitis: implications for treatment response prediction and therapeutic targets

BackgroundWhile significant research exists on gut microbiota changes after anti-tumor necrosis factor-alpha (anti TNF-α) therapy for ulcerative colitis, little is known about the longitudinal changes related to the effects of anti TNF-α. This study aimed to investigate the dynamics of gut microbiome changes during anti TNF-α (adalimumab) therapy in patients with ulcerative colitis (UC).ResultsThe microbiota composition was affected by the disease severity and extent in patients with UC. Regardless of clinical remission status at each time point, patients with UC exhibited microbial community distinctions from healthy controls. Distinct amplicon sequence variants (ASVs) differences were identified throughout the course of Adalimumab (ADA) treatment at each time point. A notable reduction in gut microbiome dissimilarity was observed only in remitters. Remitters demonstrated a decrease in the relative abundances of Burkholderia-Caballeronia-Paraburkholderia and Staphylococcus as the treatment progressed. Additionally, there was an observed increase in the relative abundances of Bifidobacterium and Dorea. Given the distribution of the 48 ASVs with high or low relative abundances in the pre-treatment samples according to clinical remission at week 8, a clinical remission at week 8 with a sensitivity and specificity of 72.4% and 84.3%, respectively, was predicted on the receiver operating characteristic curve (area under the curve, 0.851).ConclusionsThe gut microbiota undergoes diverse changes according to the treatment response during ADA treatment. These changes provide insights into predicting treatment responses to ADA and offer new therapeutic targets for UC.

Comment on “Adalimumab Dose Reduction and Withdrawal in Stable Non-Infectious Pediatric Uveitis: An Open- Label, Prospective, Pilot Study”

ABSTRACT The study by P. D. Yuan et al. titled ”Adalimumab Dose Reduction and Withdrawal in Stable Non-Infectious Pediatric Uveitis: An Open-Label, Prospective, Pilot Study” examines dose reduction and withdrawal strategies in managing pediatric uveitis with adalimumab (ADA). The study aims to optimize treatment protocols by minimizing drug exposure while maintaining disease control. However, the open-label design introduces potential bias, and the absence of a control group limits the ability to draw definitive conclusions. The small sample size and short follow-up period further constrain the study’s robustness. Methodological refinements, including a randomized controlled trial design with a larger sample size, extended follow-up, detailed adverse event data, standardized tapering protocols, and incorporation of objective outcome measures, are recommended to enhance the reliability and generalizability of the findings. These improvements could significantly inform clinical practice and contribute to the evidence base for pediatric uveitis management.

Ultrasound transmural healing correlates with higher adalimumab drug concentration in Crohn's disease only in the short-term.

Anti-TNF drugs have revolutionized the treatment of Crohn's disease (CD) and have set new therapeutic targets. A direct correlation between anti-TNF trough levels and endoscopic healing in IBD patients has been established, but the association between drug levels and transmural healing assessed by ultrasound is not yet clearly defined. To evaluate the correlation between the serum concentration of adalimumab (ADA) and sonographic transmural healing in CD patients at different times during the follow-up of patients. In this retrospective, cross-sectional study all patients with CD who were undergoing treatment with ADA in our center were included. Intestinal ultrasound (IUS) was performed before the initiation of the drug and for response monitoring. ADA serum-through levels were compared between patients with and without transmural healing at different periods of time. 92 patients were included, all patients showed signs of inflammatory activity in the baseline IUS. In the IUS monitoring of the response to ADA, 34 (34.8%) patients presented transmural healing. Among patients in the first year of treatment, those with sonographic healing showed higher median levels than patients without transmural healing (12.0 µg/mL vs. 9.3 µg/mL, respectively; p= 0.007). There was no correlation found between adalimumab levels and sonographic healing in patients undergoing treatment for over a year. Higher adalimumab through levels were corelated with transmural healing with ultrasound during the first year of treatment. This correlation was not found after one year of treatment.

Budget impact analysis of including biosimilar adalimumab on formulary: A United States payer perspective.

The biosimilar market is growing rapidly, as evidenced by 41 approvals and 37 launches to date. As adalimumab biosimilars launch in the United States, competition among biosimilar and reference adalimumab will likely increase across multiple reference indications, including rheumatology, dermatology, and gastrointestinal diseases, which may lead to decreased payer costs. To evaluate the costs of adding biosimilar adalimumab to a US commercial plan by exploring various utilization and price differential scenarios. A 3-year budget impact model for a US commercial plan of 1 million people was developed to assess switching from reference adalimumab or any self-injectable reference tumor necrosis factor (TNF) inhibitor to biosimilar adalimumab. Pharmacy and medical costs were analyzed through high- and low-conversion scenarios from reference adalimumab and the TNF inhibitor class. Price reductions of 5% to 60% relative to reference adalimumab based on previous biosimilar launches were also explored. Short-term medical costs were evaluated as additional simple and complex office visits, with scenarios of half of switch patients having 1 visit up to all switch patients having 10 visits. In a target population of 1,863 patients, switching from reference adalimumab to biosimilar adalimumab had cumulative cost savings of $5,756,073 with slow conversion (10%-20% over 3 years) and $28,780,365 with fast conversion (50%-100% over 3 years). Similar results were seen when switching from any other self-injectable reference TNF inhibitor. Cost savings more than $1 million were seen with a 10% conversion from reference adalimumab and a 15% price reduction from reference adalimumab. Additional office visit scenarios had a negligible impact on budget, with no changes in per-member-per-month costs until all switch patients had 10 additional complex visits, in which per-member-per-month costs increased by $0.02. In a hypothetical plan of 1 million lives, use of biosimilar adalimumab in commercial plans can lead to significant cost savings for payers because of increased competition. Greater and faster biosimilar conversion rates from reference adalimumab and other reference TNF inhibitors resulted in decreased costs. Additionally, even with short-term medical expenditures, cost savings were still realized when switching to biosimilar adalimumab.

Anti-TNFα in inflammatory bowel disease: from originators to biosimilars.

The introduction of anti-tumor necrosis factor α (TNFα) biologics significantly innovated inflammatory bowel disease (IBD) treatment and increased medical costs. The recent expiration of patents of some anti-TNFα biologics (such as infliximab and adalimumab) facilitated the development of biosimilars. Comparable pharmacokinetic, efficacy, safety, and immunogenicity profiles between anti-TNFα originators and biosimilars were demonstrated in different studies. Anti-TNFα biosimilars hold promise for reducing the high cost of biologics and increasing patient access to biologics. In this review, we outline the current data on the use of anti-TNFα originators and biosimilars in patients with IBD, with a focus on the efficacy, safety, and immunogenicity profiles of infliximab and adalimumab biosimilars. The potential benefits, challenges, and future directions of anti-TNFα biosimilars are also discussed in the review.

A prediction method for the individual serum concentration and therapeutic effect for optimizing adalimumab therapy in inflammatory bowel disease.

Adalimumab (ADM) therapy is effective for inflammatory bowel disease (IBD), but a significant number of IBD patients lose response to ADM. Thus, it is crucial to devise methods to enhance ADM's effectiveness. This study introduces a strategy to predict individual serum concentrations and therapeutic effects to optimize ADM therapy for IBD during the induction phase. We predicted the individual serum concentration and therapeutic effect of ADM during the induction phase based on pharmacokinetic and pharmacodynamic (PK/PD) parameters calculated using the empirical Bayesian method. We then examined whether the predicted therapeutic effect, defined as clinical remission or treatment failure, matched the observed effect. Data were obtained from 11 IBD patients. The therapeutic effect during maintenance therapy was successfully predicted at 40 of 47 time points. Moreover, the predicted effects at each patient's final time point matched the observed effects in 9 of the 11 patients. This is the inaugural report predicting the individual serum concentration and therapeutic effect of ADM using the Bayesian method and PK/PD modelling during the induction phase. This strategy may aid in optimizing ADM therapy for IBD.

Modelling the opportunity for cost-savings or patient access with biosimilar adalimumab and tocilizumab: a European perspective

Objectives Biosimilars improve patient access by providing cost-effective treatment options. This study assessed the potential for savings and expanded patient access with increased use of two biosimilar disease modifying anti-rheumatic drugs (DMARDs): (a) approved adalimumab biosimilars and (b) the first tocilizumab biosimilar, representing an established biosimilar field and a recent biosimilar entrant in France, Germany, Italy, Spain, and the United Kingdom (UK). Methods Separate ex-ante analyses were conducted for each country, parameterized using country-specific list prices, unit volumes annually, and market shares for each therapy. Discounting scenarios of 10%, 20%, and 30% were tested for tocilizumab. Outputs included direct cost-savings associated with drug acquisition or the incremental number of patients that could be treated if savings were redirected. Two biosimilar conversion scenarios were tested. Results Savings associated with a 100% conversion to adalimumab biosimilar ranged from €10.5 to €187 million (UK and Germany, respectively), or an additional 1,096 to 19,454 patients that could be treated using the cost-savings. Introduction of a tocilizumab biosimilar provided savings up to €29.3 million in the most conservative scenario. Exclusive use of tocilizumab biosimilars (at a 30% discount) could increase savings to €28.8 to €113 million or expand access to an additional 43% of existing tocilizumab users across countries. Conclusion This study demonstrates the benefits that can be realized through increased biosimilar adoption, not only in an untapped tocilizumab market, but also through incremental increases in well-established markets such as adalimumab. As healthcare budgets continue to face downwards pressure globally, strategies to increase biosimilar market share could prove useful to help manage financial constraints.

Efficacy and safety of infliximab and adalimumab in inflammatory bowel disease patients

IntroductionInflammatory bowel disease (IBD), consists of two primary types: Ulcerative Colitis (UC) and Crohn’s Disease (CD). Infliximab (IFX) and Adalimumab (ADA) are frequently utilized in the management of moderate to severe cases of IBD.AimThis study aimed to assess the efficacy and safety of IFX and ADA in individuals diagnosed with moderate to severe IBD.MethodThis study is a prospective open-labeled randomized parallel study that included moderate to severe IBD patients treated with either IFX or ADA. A total of 56 patients participated, with 34 patients received IFX and 22 patients received ADA. Various measures, including Crohn’s Disease Activity Index (CDAI), Mayo Score/ Disease Activity Index (DAI), and C-reactive protein (CRP) levels, were taken at baseline and week 14 to assess the efficacy of the treatments. In addition, the levels of drugs and sTREM-1 were measured at 14 weeks. Patient safety was monitored throughout the study period.ResultsIn the group received IFX, there was a notable decrease in CDAI (P = 0.045), DAI (P = 0.026), and CRP (P = 0.023 for CD, and P = 0.021 for UC) levels. In addition, the group received ADA experienced a significant reduction in CDAI (P = 0.001), DAI (P = 0.032), and CRP (P < 0.018 for CD and P = 0.003 for UC) levels. Responders had higher drug concentrations than non-responders, notably IFX concentration was higher in responders with CD (P = 0.001) and UC (P < 0.001). ADA concentration was higher in UC (P <= 0.001) and all CD patients responded to the treatment. The same trend was observed for sTREM-1 levels in CD and UC patients (P = 0.042, and P = 0.015, respectively) in the IFX group. In UC patients treated with ADA, the level of sTREM-1 was significantly low (P = 0.002).ConclusionBoth IFX and ADA have a good safety profile and deliver a beneficial clinical and laboratory response in moderate-severe IBD patients.Clinical Trial RegistrationThis study is registered on ClinicalTrials.gov under the identifier NCT05291039. (You can access the study at https://clinicaltrials.gov/study/NCT05291039 (First Posted: March 22, 2022).

Comparison of Two Financial Incentives to Encourage the Use of Adalimumab Biosimilars: Results of a French Experiment Close to Clinicians.

In 2018, the French government introduced two mutually exclusive financial incentives to increase etanercept and insulin glargine biosimilar use. The general case redirects 20% of the price difference between the reference product and its biosimilars to hospitals for every biosimilar dispensed in community pharmacies from hospital prescriptions. The experimental case redirects 30% to prescribing clinical units after hospital selection. Adalimumab was added to these incentives in 2019, after its first biosimilar was launched. This retrospective observational study aimed to compare both general and experimental incentives after 19 months to assess the impact of directly incentivizing clinical units for adalimumab biosimilars. The monthly number of adalimumab boxes dispensed in community pharmacies was linked to the corresponding hospital's prescription using IQVIA Xponent data from November 2017 to October 2020. The monthly mean rate of adalimumab biosimilars was compared between incentive groups and subgroups depending on hospitals' prior experience with the etanercept experimental case. General case hospitals had a significantly lower mean biosimilar uptake (16.7% vs 23.2%, p = 0.029) than those included in the experimental case. Twenty-three of the 40 hospitals in the experimental case and ten out of the 91 hospitals studied in the general case had already taken part in the etanercept experiment. Biosimilar uptake was higher, but not statistically significant, for hospitals with prior experience in the adalimumab general case group (p = 0.086). This study confirmed that incentivizing close to physicians was more effective in increasing the biosimilar rate. It also suggested that previous incentive experience positively influenced biosimilar penetration.

Clinical Course of Bio Naive Ulcerative Colitis Patients Five Years After Initiation of Adalimumab in a Nationwide Cohort.

There is limited data on the long-term clinical outcomes of bio-naïve ulcerative colitis (UC) patients who are initiated on adalimumab (ADA). Our study aims to evaluate the clinical course of a nationwide cohort of bio naïve UC patients who were started on ADA, and then followed for 5 years after initiation of the drug. We conducted a retrospective cohort study using the US Veteran Affairs Healthcare System (VAHS). Bio naïve UC patients were followed for 5 years after initiation of ADA. The primary outcome was to determine the time to discontinuation of ADA and if patients achieved endoscopic remission by the end of follow-up. A total of 387 patients were included among whom 193 (49.87%) had pancolitis. The highest rate of ADA discontinuation was within the first year, with the elderly having a higher rate of discontinuation (HR 1.67, 95% CI: 1.14-2.45) and those on concomitant immunomodulators having a lower rate of discontinuation (HR 0.70, 95% CI: 0.48-1.03). In total, 125 (32.30%) patients remained on ADA at the end of their maximum follow-up. 54 (43.90%) achieved endoscopic remission. Among bio-naive UC patients who were started on ADA, a third were still on the drug at the end of 5 years and half had endoscopic remission. The rate of discontinuation was highest within the first year of initiation, but patients continued to stop the drug over the course of follow-up.

Cost-Effectiveness of Biosimilars vs Leflunomide in Patients With Rheumatoid Arthritis

Among patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate, a treatment sequence initiated with biosimilar disease-modifying antirheumatic drugs (DMARDs) provides better clinical efficacy compared with conventional synthetic DMARDs recommended by current treatment guidelines; but its cost-effectiveness evidence remains unclear. To evaluate the cost-effectiveness of the treatment sequence initiated with biosimilar DMARDs after failure with methotrexate vs leflunomide and inform formulary listing decisions. This economic evaluation's cost-effectiveness analysis was performed at a Hong Kong public institution using the Markov disease transition model to simulate the lifetime disease progression and cost for patients with RA, using monetary value in 2022. Scenario and sensitivity analyses were performed to test the internal validity of the modeling conclusion. Participants included patients diagnosed with RA from 2000 to 2021 who were retrieved retrospectively from local electronic medical records to generate model input parameters. Statistical analysis was performed from January 2023 to March 2024. The model assesses 3 competing treatment sequences initiated with biosimilar infliximab (CT-P13), biosimilar adalimumab (ABP-501), and leflunomide; all used in combination with methotrexate. Lifetime health care cost and quality-adjusted life-years (QALYs) of the simulated cohort. In total, 25 099 patients with RA were identified (mean [SD] age, 56 [17] years; 19 469 [72.7%] women). In the base-case analysis, the lifetime health care cost and QALYs for the treatment sequence initiated with leflunomide were US $154 632 and 14.82 QALYs, respectively; for biosimilar infliximab, they were US $152 326 and 15.35 QALYs, respectively; and for biosimilar adalimumab, they were US $145 419 and 15.55 QALYs, respectively. Both biosimilar sequences presented lower costs and greater QALYs than the leflunomide sequence. In the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (US$/QALY) comparing biosimilar infliximab sequence vs leflunomide sequence and biosimilar adalimumab sequence vs leflunomide sequence ranged from -15 797 to -8615 and -9088 to 10 238, respectively, all below the predefined willingness-to-pay threshold (US $48 555/QALY gain). In the probabilistic sensitivity analysis, the probability of treatment sequence initiated with leflunomide, biosimilar infliximab, and biosmilar adalimumab being cost-effective out of 10 000 iterations was 0%, 9%, and 91%, respectively. In this economic evaluation study, the treatment sequences initiated with biosimilar DMARDs were cost-effective compared with the treatment sequence initiated with leflunomide in managing patients with RA who experienced failure with the initial methotrexate treatment. These results suggest the need to update clinical treatment guidelines for initiating biosimilars immediately after the failure of methotrexate for patients with RA.

Predictive factors and adalimumab efficacy in managing chronic recurrence Vogt-Koyanagi-Harada disease

BackgroundThis study explores prognostic factors influencing Vogt-Koyanagi-Harada (VKH) disease and observes the efficacy and safety of Adalimumab (ADA) in treating recurrence in Vogt-Koyanagi-Harada (VKH) patients.MethodsA retrospective study was conducted on all patients diagnosed with VKH disease at Beijing Tongren Hospital between 2020 and 2023. Clinical data included initial and final visual acuity, age, gender, ocular complications, treatment modalities, disease duration, and recurrence frequency.ResultsA total of 62 VKH patients were included, comprising 34 in the acute-resolved group and 28 in the chronic-recurrent group. The mean age of patients in the acute-resolved group was 38.29 ± 15.46 years, while the mean age of chronic-recurrent group had a 49.00 ± 16.43 years. Initial best-corrected visual acuity (BCVA) examination at the first visit showed an average BCVA of 0.64 ± 0.29 logMAR in the acute-resolved group and 1.38 ± 0.54 logMAR in the chronic-recurrent group (p = 0.002). During follow-up, ocular complications were observed in 29.4% of the acute-resolved group patients and 41.7% of the chronic-recurrent group patients (P = 0.006). “Sunset glow fundus” was observed in 23.5% of the acute-resolved group and 64.3% of the chronic-recurrent group patients (P = 0.001). Poor initial BCVA (P = 0.046) and the occurrence of “sunset glow fundus” (P = 0.040) were significantly associated with progression to the chronic recurrent phase. Logistic regression analysis revealed that older age at onset (P = 0.042) and the occurrence of “sunset glow fundus” (P = 0.037) were significant predictors for progression to the chronic recurrent phase. ADA significantly reduced anterior chamber inflammatory cells (P = 0.000) and vitreous cavity inflammatory cells (P = 0.001) in the chronic-recurrent group, and markedly decreased the recurrence rate in VKH patients (P = 0.009).ConclusionIn comparison to acute-resolved patients, chronic-recurrent patients exhibited poorer initial BCVA and a significantly increased incidence of “sunset glow fundus.” Older age at onset and the occurrence of “sunset glow fundus” at diagnosis are crucial predictive factors for VKH patients progressing to the chronic recurrent phase. ADA effectively alleviates refractory VKH disease and is generally well-tolerated.

Guselkumab Reduces Disease- and Mechanism-Related Biomarkers More Than Adalimumab in Patients with Psoriasis: A VOYAGE 1 Substudy

Psoriasis is an immune-mediated inflammatory disease characterized by activation of IL-23-driven IL-17-producing T cell and other IL-23 receptor-positive IL-17-producing cell responses. Selective blockade of IL-23p19 with guselkumab was superior to blockade of TNF-α with adalimumab (ADA) in treating moderate-to-severe psoriasis. Objective: Pharmacodynamic responses of guselkumab versus ADA were compared in patients with psoriasis in VOYAGE 1. Inflammatory cytokine serum levels were assessed (n= 118), and lesional and nonlesional skin biopsies were collected (n= 38) in patient subsets at baseline and 4, 24, and 48 weeks after treatment to evaluate pharmacodynamic responses of guselkumab versus those of ADA. Guselkumab provided rapid reductions in serum IL-17A, IL-17F, and IL-22 levels by week 4 versus at baseline, which were maintained through weeks 24 and 48 (P < .001). The magnitude of reduction of IL-17A and IL-22 at week 48 and IL-17F at weeks 4, 24, and 48 were greater with guselkumab than with ADA (all P < .05). In the skin, guselkumab reduced the expression of IL-23/IL-17 pathway-associated and psoriasis-associated genes. These data provide extensive characterization of pharmacodynamic anti-inflammatory responses to IL-23p19 and TNF-α inhibition in human blood and tissue over time with FDA-approved doses of guselkumab and ADA. Trial registration:ClinicalTrials.govClinicalTrials.gov (NCT02207231).

Efficacy and Safety of Infliximab Versus Adalimumab in Adult Subjects With Moderate to Severe Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Ulcerative colitis (UC) is an inflammatory disorder affecting the colon, and typically, during the disease course, the condition may exacerbate, relapse, and remit. One of the most successful lines for inducing and maintaining clinical remission in subjects with UC is biological therapy with anti-tumor necrosis factor α (anti-TNF) agents, including adalimumab (ADA) and infliximab (IFX).This meta-analysis is an attempt to obtain complementary information driven by real-world experience (RWE) concerning the efficacy and safety of two of the most popular anti-TNFs in treating UC.This is a systematic review and meta-analysis of RWE studies comparing ADA and IFX as naïve anti-TNF agents for the treatment of subjects with UC. Studies were obtained by searching Scopus, Google Scholar, the Cochrane Central Register of Controlled Trials, Embase, and the PubMed Central databases.Patients treated with IFX showed significantly higher induction responses. No statistically significant difference was found in the comparison of response in the maintenance treatment period. Higher overall adverse events were related to IFX treatment, with serious adverse events that were nonsignificantly higher in the ADA-treated group.In conclusion, IFX demonstrated significantly higher induction responses compared to ADA in patients with moderate-to-severe UC. IFX was associated with higher overall adverse events, whereas serious adverse events were non-significantly higher in the ADA-treated group. IFX may be favored as a first-line agent for its induction efficacy, and the choice between IFX and ADA should be individualized based on comprehensive clinical evaluation.

Sustaining competition for biosimilars on the pharmacy benefit: Use it or lose it.

Congress passed the Biologic Price Competition and Innovation Act of 2009, specifically to offer market competition as a counterweight to the rising costs of biologic medicines. As of April 15, 2024, 49 biosimilars have been approved by the US Food and Drug Administration in 15 biologic categories. Biosimilar competition has been undeniably successful: Through 2022, biosimilars have saved the US health system $23.6 billion, without significant care disruption or reduced quality. Through 2023, adalimumab biosimilar competition has added an additional $6.5 billion to this total, primarily through greater rebates from the reference manufacturer. Despite launching at discounts as great as 85%, adalimumab biosimilars have not been given preferred formulary positioning in the vast majority of cases and have thus gained only 3% of market share through 2023, largely because of payers' and pharmacy benefit managers' preference for rebates over discounts. This situation may negatively influence future biosimilar development, posing a threat to a biosimilar pipeline that represents hundreds of billions in savings over the next 10 years.

Long-Term Survival of Subcutaneous Biosimilar Tumor Necrosis Factor Inhibitors Compared to Originators: Results From a Multicenter Prospective Registry.

To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. No significant differences were found between treatments in long-term survival due to inefficacy or AEs.

EE375 Cost Savings and the Opportunity for Expanded Treatment Access with Increased Use of Biosimilar Adalimumab in the United States

EE375 Cost Savings and the Opportunity for Expanded Treatment Access with Increased Use of Biosimilar Adalimumab in the United States

Benefits of Biosimilars in the Management of Patients with Inflammatory Bowel Disease: An International Survey.

Background/Objectives: The development of biosimilar drugs has revolutionized the management of patients with inflammatory bowel diseases (IBD), significantly reducing healthcare costs. However, the impact of biosimilar availability on patient care is unknown. We conducted a survey to investigate the benefits of using biosimilars in patients with IBD. Methods: Physicians involved in the IBD care were invited to participate in an anonymous online survey. The questionnaire consisted of 42 questions addressing availability, cost, recommendations, and positioning regarding the use of biosimilars. Results: A total of 233 physicians (88.4% gastroenterologists) from 63 countries worldwide participated in the survey. Most respondents had >10 years of practice (202/233, 85.9%). Biosimilars were available in almost all cases (221, 94.8%), and over two-thirds of respondents had more than one biosimilar of adalimumab or infliximab on hospital formulary. In most cases, adalimumab and infliximab biosimilars had a reduced cost of at least 30% compared to the originators. The savings resulting from the use of biosimilars allowed physicians to improve patient care (3/233, 1.3%) or to improve research (2/233, 0.8%) in only a few cases. Interestingly, for about 50% of respondents, the cost of biologics was a limitation for patient access to therapy. For the majority of participants, the availability of biosimilars did not influence treatment decisions in Crohn's disease (70/165, 42.4%) and ulcerative colitis (83/165, 50.3%). Conclusions: The reduced cost of biosimilars compared to reference products is the main driver of choice in IBD. The impact of biosimilars of ustekinumab and vedolizumab in improving access to therapies and changing the treatment algorithm remains to be defined.

Population Pharmacokinetic Analysis and Simulation of Alternative Dosing Regimens for Biosimilars to Adalimumab and Etanercept in Patients with Rheumatoid Arthritis.

Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient's circulating drug levels. Using modelling and simulation, the aim of this study was to investigate whether adalimumab and etanercept biosimilar dosing intervals can be altered to achieve therapeutic drug levels at a faster/similar time compared to the recommended interval. RA patients starting subcutaneous Amgevita or Benepali (adalimumab and etanercept biosimilars, respectively) were recruited and underwent sparse serum sampling for drug concentrations. Drug levels were measured using commercially available kits. Pharmacokinetic data were analysed using a population approach (popPK) and potential covariates were investigated in models. Models were compared using goodness-of-fit criteria. Final models were selected and used to simulate alternative dosing intervals. Ten RA patients starting the adalimumab biosimilar and six patients starting the etanercept biosimilar were recruited. One-compartment PK models were used to describe the popPK models for both drugs; no significant covariates were found. Typical individual parameter estimates were used to simulate altered dosing intervals for both drugs. A simulation of dosing the etanercept biosimilar at a lower rate of every 10 days reached steady-state concentrations earlier than the usual dosing rate of every 7 days. Simulations of altered dosing intervals could form the basis for future personalised dosing studies, potentially saving costs whilst increasing efficacy.

A randomised, crossover trial exploring the patient perspective and effectiveness of biosimilar adalimumab transition: IBD reference and biosimilar adalimumab cross over study (iBaSS).

Patient satisfaction has been positively associated with adherence which is expected to impact outcomes. Although vital for successful implementation of biosimilar medicines, little is known about the patient perspective of transition. The aim of this study was to investigate clinical outcomes and patient experience of transitioning between reference adalimumab and a biosimilar (SB5). iBaSS is a phase IV single-centre, prospective, randomised, single-blind, cross-over study in adult subjects with Crohn's disease. Participants, stable on adalimumab before consent, received 24weeks of treatment with both reference adalimumab and SB5. The primary outcome was the proportion of patients maintaining baseline clinical status throughout each treatment period, with patients' perspective of disease control and treatment satisfaction assessed as secondary outcomes. A total of 112 participants, representative of the heterogeneous patient populations encountered in routine clinical practice, were enrolled. A similar proportion of participants maintained baseline clinical status through each treatment period: 81.8% with reference adalimumab and 79.5% with SB5. Patient reported outcomes (IBD-Control questionnaire (SB5: 15.5; reference adalimumab 15) and TSQM), adverse events and therapeutic drug monitoring remained consistent through both treatment periods, although a higher median injection pain VAS score was noted with SB5 (53/100 versus 6/100 with reference adalimumab). The number of switches undertaken in the study did not impact serum drug concentration or immunogenicity. This study, mimicking real world adalimumab transition, demonstrates that patients undertaking brand transition can be expected to have consistent clinical and satisfaction outcomes. Number 2018-004967-30.