Biosimilar Infliximab Research Articles

P753 Comparing long-term outcomes in inflammatory bowel disease patients between switch and non-switch cohorts: no differences in infliximab persistence or safety outcomes after 54 months

Abstract Background Switching patients with inflammatory bowel disease (IBD) from originator to biosimilar infliximab has been demonstrated to be non-inferior to continuing originator infliximab by several studies. However, data comparing treatment outcomes beyond 12-months across switch and non-switch cohorts specific to IBD patients remains comparatively underreported. Here we report long-term (>48 weeks) treatment outcomes of the SAME study, a large-scale parallel cohort study of Australian IBD patients who underwent non-medical switching from originator to biosimilar (CT-P13) (n=204) or continued originator infliximab (n=141). Methods The SAME study was a multi-centre, prospective parallel cohort non-inferiority study across seven Australian hospitals over 48 weeks undertaken between May 2017 to October 2019. The data that we present here is the long-term extension study, obtained retrospectively, which sought to compare long-term infliximab persistence beyond 48 weeks across switch and non-switch cohorts. This study included five of the original seven sites, three of which switched from originator to biosimilar infliximab. The primary outcome was infliximab persistence, defined as the proportion of originator or biosimilar infliximab treated patients from the original cohort at last follow up. Secondary outcomes included disease worsening requiring infliximab dose escalation or discontinuation, rates of adverse events, and development of antibodies to infliximab (>10ng/mL). Results Data from 263 (90 Ulcerative colitis and 173 Crohn’s disease) of 345 (76%) patients enrolled in the original SAME study were included with median follow up of 54.2 months (IQR 46.1-59.3). At last follow-up, 103 (65.5%) and 68 (64.2%) patients across the switch and non-switch cohorts (p = 0.8) remained on infliximab. There were no differences in the proportions that discontinued infliximab due to clinical or biochemical worsening of disease (21.7 v 23.6%, p = 0.72); required infliximab dose escalation (35.2 v 32.4%, p=0.8); developed antibodies to infliximab (5.3 vs 11.3%, p = 0.09) or experienced drug related adverse events (7.8 vs 8.3%, p = 0.8) between switch and non-switch cohorts, at last follow-up. Conclusion Long-term infliximab persistence was similar between switch and non-switch cohorts after a median of 54 months. This study represent one of the longest ‘real-world’ comparisons between switch and non-switch cohorts specific to IBD, and should provide reassurance to clinicians and patients alike.

P750 Biosimilar Infliximab Switching is Not Associated with Adverse Outcomes: A Real-World Effectiveness Analyses in a National U.S. Cohort of U.S. Military Veterans with Inflammatory Bowel Disease

Abstract Background Infliximab (IFX) biosimilars are widely available for Crohn’s disease (CD) and ulcerative colitis (UC). However, implementation of biosimilar switching has been highly variable in the U.S. Barriers to switching include patient and provider concerns of lower efficacy, immunogenicity, and safety. Biosimilar switching in Veterans Affairs (VA) was based on local facility policy rather than patient/provider selection and thus less prone to selection bias. The goal of this study is to evaluate the safety and effectiveness of biosimilar switching in a National U.S. Cohort of Veterans with CD and UC. Methods We conducted a retrospective cohort study of CD and UC patients who received maintenance originator IFX from 2017-2019 in the VA. CD and UC patients were identified using a previously validated algorithm and confirmed by chart review. Patents on maintenance IFX originator were identified by dispensed medication from Corporate Data Warehouse (CDW). Patients switched to IFX biosimilar after 2017 were identified in CDW by dispensed medication and confirmed by chart review. Adverse outcomes were defined as infusion reaction, serious infection (intravenous antibiotic, delay of IFX), immunogenicity (anti-IFX antibody or IFX escalation) or disease flare (escalation of steroid, IBD related Emergency department visit, hospitalization) confirmed by chart review. Adverse event rates at 12 months for patients continued on originator IFX were compared to patients switched to IFX biosimilar using univariate and multivariate logistic regression models adjusting for patient and non-patient factors. Results A total of 790 patients (492 CD, 298 UC) on originator IFX were identified during the study period. Of these, 380 patients were identified to have switched to IFX biosimilar and 410 patients continued on IFX originator during the study period. Overall adverse outcomes occurred in 35.6% of patients at 12 months (35.6% switch, 35.3% non-switch, p=0.87). No statistically significant difference in rates of infusion reaction, serious reaction, immunogenicity, or IBD flare were identified between switch and non-switch groups. In multivariate logistic regression including age, race, gender, concomitant medication, and VA priority status, no significant differences in adverse outcomes at 12 months were observed between switch and non-switch groups (aOR 1.09, 95% CI 0.76-1.42). Conclusion In a real-world national U.S. cohort of patients with CD and UC, we observed IFX biosimilar switching was not associated with adverse events compared to continuation on IFX originator. While this study may be underpowered to detect such a small difference, these findings provide further reassurance that IFX biosimilar switching for CD and UC is safe and effective.

P383 Real-life experience of the efficacy, safety and pharmacokinetic data of switching from intravenous to subcutaneous infliximab in inactive inflammatory bowel disease patients. Results from the ENEIDA registry.

Abstract Background Recently, a subcutaneous formulation of biosimilar infliximab (CT-P13) (SC-IFX) has been approved for inflammatory bowel disease (IBD). The aims of this study were to evaluate efficacy, safety, pharmacokinetics and patient experience following a switching to SC-IFX in patients who are in clinical remission on IV-IFX maintenance treatment. Methods Multicentre, descriptive, and observational study including Crohn’s disease (CD) and ulcerative colitis (UC) patients who were going to be changed from IV-IFX to SC-IFX on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD–GETECCU). All patients were on clinical and biological remission at least 24 weeks before changing. Demographic and disease data, clinical activity (Harvey-Bradshaw index for CD and mayo index for UC), analytical data (C reactive protein (CRP) and fecal calprotectin (FC), as well as trough levels were collected at baseline, at 12 and 24 weeks. Results One hundred and fifty-five patients were included: 54 UC (35%) and 91 (65%) CD; 44% women and 56% men; age 45.5 years (32-55). IV-IFX was mainly administered due to active disease (72%) and perianal disease (7%) and during 32 months [range 14-56]. Pre-switch, 78 (50.3%) were on 8-weekly dosing of IV-IFX, 77 (49.7%) were with intensification dose and the half (50.3%) were on concomitant immunomodulatory therapy. SC-IFX was mainly switching by COVID-19 pandemic (60%), to increase through levels (15%) or patient request (25%). The majority of patients (140, 90%) remained with standard dose, 8 (5%) required dose intensification (120 mg weekly in 4 and 240 mg every 2 weeks in 4) and 7 (4.5%) had successful de-escalation (120 mg every 3 weeks in 4 and 120 mg every 4 weeks in 3). Clinical indices, CRP levels and FC remained unchanged (Figure). Median SC-IFX levels significantly increased from baseline of 4.5 μg/dl [range 2.6-9.2] to 14 μg/dl [range 9.5-16.2] at week 12 and 13.2 μg/dl [range 10.4-19.7] at week 24. No factors (immunossupresor, body mass index, disease location) were associated with the increase of IFX trough levels. During 24 weeks of follow-up, 16 of the 78 patients (20.5%) stopped immunosuppressant treatment. The adverse events were recorded in 9 patients (5.8%), 4 (2.6%) were hospitalized and 4 (2.6%) had surgery (one of them for perianal disease). Nine patients (5.8%) stopped SC-IFX (1 primary failure, 2 loss of response, 4 adverse events, 1 voluntarily, and 1 surgery). Conclusion The switch from IV to SC IFX maintains clinical remission safely in IBD patients, offers higher drug levels and a good patient acceptance. However, the significance of higher drug levels with SC-IFX requires further exploration.

P745 Multiple infliximab biosimilar switches appear to be safe and effective in a real-world inflammatory bowel disease cohort

Abstract Background Switching from originator to biosimilar infliximab (IFX) is effective and safe. However, data on multiple switching are scarce. The Edinburgh IBD unit has undertaken three switch programmes: (1) Remicade to CT-P13 (2016), (2) CT-P13 to SB2 (2020), and (3) SB2 to CT-P13 (2021). The primary endpoint of this study was to assess CT-P13 persistence following switch from SB2. Secondary endpoints included persistence stratified by the number of biosimilar switches (single, double and triple), effectiveness and safety. Methods We performed a prospective, observational, cohort study. All adult IBD patients on IFX biosimilar SB2 underwent an elective switch to CT-P13. Patients were reviewed in a virtual biologic clinic with protocol driven collection of clinical disease activity, CRP, faecal calprotectin (FC), IFX trough / antibody levels, and drug survival. Results 297 patients (CD n=196 [66%], UC/IBDU n=101, [34%]) were switched. This was the third, second and first IFX switch for 67 /297 (22.5%), 138 /297 (46.5%) and 92 /297 (31%) of the cohort respectively. Patients who underwent multiple IFX biosimilar switches had longer disease duration (p=0.0001) and IFX duration (p=0.0001) and were less often on combination therapy with an immunomodulator (p=0.0001). 90.6% of patients remained on IFX during a median follow-up of 7.5 months [6.8-8.1] (figure 1). The number of switches was not independently associated with IFX persistence after adjusting for confounders (table 1). Clinical (p=0.77), biochemical (CRP ≤5mg/mL; p=0.75) and faecal biomarker (FC<250µg/g; p=0.63) remission were comparable at baseline, week 12 and week 24 (figure 2). Conclusion Multiple successive switches from IFX originator to biosimilars are effective and safe in patients with IBD, irrespective of the number of IFX switches.

P488 Switch from intravenous to subcutaneous infliximab in patients with Inflammatory Bowel Disease: efficacy, safety and patients’ acceptance

Abstract Background A new formulation of biosimilar infliximab (IFX) has recently been approved for subcutaneous administration (SC) that may offer pharmacokinetic advantages resulting in higher drug exposure. Our purpose was to evaluate the efficacy, safety, pharmacokinetic changes and patients’ acceptability after switching from intravenous (IV) to SC IFX in a cohort of patients with Inflammatory Bowel Disease (IBD) in clinical practice. Methods Observational, prospective and single-center study including patients with IBD in sustained (≥6 months) clinical remission under IV IFX that were switched to SC IFX 120 mg every 2 weeks. Prospective monitoring was performed with clinical and laboratory data including IFX trough levels prior to the last IV infusion (W-IV), prior to the first SC administration (W-0), and after 16 weeks (W-16) and 52 weeks (W-52) of SC treatment. Patients’ satisfaction has been evaluated at W-52. A descriptive analysis of the data has been carried out with the R Studio statistical program using means and Wilcoxon signed rank test. Results Sixty patients have been included, all have achieved W-16 and twelve W-52. Thirty-five (58,3%) are men with a median age of 42,5 (20-71) years. Thirty-eight (63,3%) have Crohn’s disease and twenty-two (36,7%) ulcerative colitis, with a median disease duration of 11,3 years. They have been receiving IV IFX (5mg/kg/8 weeks in 95% of cases) for 5,7 (0,6-21,1) years, at a stable dose (≥6 months). Twenty-seven (45%) received concomitant immunomodulatory treatment and IFX was the first biological in 75% of patients. None of the patients presented clinical relapse during follow-up (Table 1). Median trough IFX levels under IV treatment were 3,9 µg/dl (W-IV) and 4,3 µg/dl (W-0). Compared to W-0, IFX trough levels were significantly higher both in W-16 [17,05 µg/dl (5,59–57,60), p<0,005] and in W-52 [16,75 µg/dl (8,65 –35,01), p=0,007], without significant differences between W-16 and W-52 (p=0,74) (Figure 1). None of the patients developed immunogenicity. Three adverse effects have been detected: 1 allergic reaction to the first SC dose and 2 mild skin reactions. At W-16 and W-52 the number of patients maintaining SC IFX treatment were 58/60 (96,7%) and 10/12 (83,4%) respectively. At W-52, all patients expressed high satisfaction with the change and would not like to return to IV treatment. All place the SC route as a preference above the IV. Conclusion Switching from IV to SC IFX is safe, effective, and well accepted by patients with stable IBD. A significant increase in IFX trough levels is observed with the SC formulation.

Immunogenicity of the biosimilar CT-P13 infliximab or the original infliximab in Iraqi patients with Ankylosing spondylitis does not correlate with their demographic characteristics

Background: Ankylosing spondylitis is a rare disease affecting people with hereditary factors. Its treatment includes life style modification and use of drugs such as the biologic agent infliximab or its biosimilar, CT-P13 infliximab. Despite their therapeutic usefulness, these agents are associated with a number of serious adverse effects such as immunogenicity. Objectives: The aim of current study was to investigate if immunogenicity of the biosimilar CT-P13 infliximab or the original infliximab, in Iraqi patients with Ankylosing spondylitis, is affected by any of the patients’ demographic characteristics. Methods: A retrospective open-label study was conducted from December 2021 to March 2022 at the Rheumatology Unit, Baghdad Teaching Hospital/Medical City, Baghdad. Forty-four patients were taking Infliximab, and another 50 patients were taking CT-P13, both at a dose of 5mg/kg for 3 months prior to recruitment in current study. Disease activity was assessed by ASDAS-CRP score while antibodies and C-reactive protein were tested by Enzyme-Linked Immunosorbent Assay technique. Statistical analyses were performed using SPSS statistical package for Social Sciences version 20.0. The level of significance was considered at P<0.05. Results: There was non-significant correlation between anti-infliximab antibodies and demographic data of patients (P>0.05). Similar data were reported regarding the biosimilar CT-P13 infliximab except for smoking and disease activity which exhibited significant correlation with development of anti-CT-P13 antibodies (P<0.05). Conclusion: Immunogenicity of the biosimilar CT-P13 infliximab, but not that of the original Infliximab, may be influenced by demographic characteristics or disease activity in patients with ankylosing spondylitis.

Safety and Effectiveness of SB2 (Infliximab Biosimilar) in Adult Patients with Immune-Mediated Inflammatory Diseases: A Post-Marketing Surveillance in Korea.

SB2 is a biosimilar of infliximab (IFX), which is approved for rheumatoid arthritis (RA), ankylosing spondylitis (AS), adult and pediatric Crohn's disease (CD), adult and pediatric ulcerative colitis (UC), psoriatic arthritis (PsA), and plaque psoriasis (PsO). The drug approval process in Korea includes post-marketing surveillance (PMS) studies to re-examine the safety and effectiveness of approved new medications. This was a prospective, multi-center, open-label, observational, phase 4 PMS study of IFX-naïve patients or patients switched from reference IFX or another IFX-biosimilar to SB2 in all approved indications. The primary endpoint was to evaluate the safety of SB2 reported as adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was to evaluate the effectiveness measured as investigators' overall effectiveness assessment, categorized as improved, stable, or worsened. Furthermore, disease-specific activity scores were collected for each indication [28-joint Modified Disease Activity Score (DAS28) for RA, Korean Bath Ankylosing Spondylitis Disease Activity Index (KBASDAI), Crohn's Disease Activity Index (CDAI), and Full Mayo Score for UC]. In the safety and effectiveness analysis, 180 and 128 patients were included, respectively. Most patients (83.9%) were IFX-naïve patients and 16.1% were switched patients. RA (48.9%) and AS (31.1%) were the most frequent indications. Overall, 23 (12.8%) patients reported AEs and 14 (7.8%) patients reported ADRs. Serious adverse events (SAEs) were reported by 3 (1.7%) patients. As per investigators' overall effectiveness assessments, SB2 was effective in 94.6% (105/111) of IFX-naïve patients and 82.4% (14/17) of switched patients. In IFX-naïve patients, disease activity scores decreased significantly from baseline to week 30 (week 24 for AS); mean (SD) changes of disease scores for each indication were DAS28 - 1.9 (0.79) for RA, KBASDAI - 3.8 (1.68) for AS, CDAI - 200.4 (112.47) for CD, and Full Mayo Score - 6.6 (2.92) for UC. The persistence rate of SB2 treatments was 88.3% with median treatment duration of 30.1weeks. This PMS study of the IFX-biosimilar SB2 in Korea confirmed the safety and effectiveness of SB2 in major indications.

Population Pharmacokinetics of CMAB008 (an Infliximab Biosimilar) and Remicade® in Healthy Subjects and Patients with Moderately to Severely Active Rheumatoid Arthritis.

CMAB008 is a monoclonal antibody developed as a biosimilar to infliximab (Remicade®, Janssen). The pharmacokinetic characteristics of CMAB008 and Remicade® in healthy subjects and patients with moderately to severely active rheumatoid arthritis (RA) were investigated using a population modeling approach, and the pharmacokinetic similarity of CMAB008 to Remicade® was assessed. The population pharmacokinetic model was developed on the basis of intensive pharmacokinetic data from a phase1 study in healthy male subjects and combined intensive and sparse pharmacokinetic data from a phase3 study in patients with RA. A two-compartment model with first-order elimination adequately described CMAB008 and Remicade® concentration data in healthy subjects and patients with RA. The analysis of covariates identified anti-drug antibody (ADA), neutralizing antibody (NAB), real-time body weight (BWT), and real-time albumin (ALB) as significant covariates on clearance, and BWT was also a significant covariate for the central volume of distribution. The treatment type (CMAB008 versus Remicade®) and the study population (healthy subjects versus patients with RA) were not identified as significant covariates on the pharmacokinetics of infliximab, demonstrating pharmacokinetic similarity between CMAB008 and Remicade® in both study populations. The effect of BWT and ALB changes on exposures to infliximab was within the acceptable range, suggesting that the 3mg/kg regimen is appropriate in clinical practice for patients with RA and BTW and ALB distribution within the range evaluated in the current analysis. The pharmacokinetic characteristics were similar between CMAB008 and Remicade® in healthy subjects and patients with RA. CMAB008 can be considered bioequivalent to Remicade®. ClinicalTrials.gov identifiers NCT04779892, NCT03478111.

Evaluating the benefits of TNF-alfa inhibitor biosimilar competition on off-patent and on-patent drug markets: A Southern European analysis.

Background: The level of competition achieved following biosimilars market availability varies by country, care setting and molecule. Hence, biosimilars contribution to attaining price reductions and extended access to treatments can also vary. Objective: The aim of this study is to capture market dynamics for tumor necrosis factor (TNF)-alpha inhibitors and competing molecules in Southern European markets (2011-2020), and to evaluate the benefits of the competition generated by the availability of biosimilars. Methods: This study is based on a literature review examining market characteristics for TNF-alfa inhibitors and competing immunomodulator molecules, and on the quantitative analysis of market data for these molecules in Italy, Portugal and Spain. Results: Following biosimilars availability in Italian, Portuguese and Spanish markets, there has been an expansion in the overall access to TNF-alfa inhibitor pharmaceuticals. Further, savings have been generated within the TNF-alfa inhibitors class even after the increased use of these molecules. However, the potential of infliximab, etanercept and adalimumab biosimilars to generate price competition outside of their own drug class appeared limited in the studied markets. Considering this limitation and that shifts towards on-patent and higher-cost therapies have occurred after TNF-alfa inhibitor biosimilars availability, the importance of investing in biosimilars development for still on-patent immunology biologics is emphasized. Conclusion: This study highlights the need for policies that do not only seek higher utilization of biosimilars, but that also support a sustainable market for these products. This is expected to foster the future development of biosimilar medicines.

PERFUSE: Non-Interventional Cohort Study of Patients Receiving Infliximab Biosimilar SB2: Results in Pediatric Patients.

PERFUSE is a non-interventional study of 1233 patients [inflammatory rheumatic disease, n = 496; inflammatory bowel disease (IBD), n = 737] receiving infliximab (IFX) biosimilar SB2 therapy. This analysis describes response to treatment and persistence on SB2 for up to 12 months in pediatric IBD patients (n = 126). Pediatric IBD patients with Crohn disease (CD) or ulcerative colitis (UC), either naïve or switched from originator IFX, who started SB2 in routine practice after September 2017 were eligible. Data were captured for 12 months following SB2 initiation. Disease activity was measured using C-reactive protein (CRP) levels and the Harvey-Bradshaw Index or Pediatric Ulcerative Colitis Activity Index for CD and UC patients, respectively. Body mass index and height z scores were used to assess patient growth between initiation (M0) and month 12 (M12). One hundred twenty-six pediatric IBD patients were included (102 CD patients, 51 naïve and 51 switched; 24 UC patients, 9 naïve and 15 switched). Naive patients' disease scores decreased between M0 and M12. CRP measurements also decreased in naïve CD patients. Switched patients' disease scores and CRP levels remained stable between M0 and M12. Height z scores improved significantly over the course of the treatment for all groups except for naïve UC patients. SB2 provides effective disease control for naïve and switched pediatric patients. Clinical remission rates improved in naïve patients and no loss of control was observed in switched patients after 1 year. Growth failure is not observed in IBD patients under SB2 treatment.

Cost-Utility Analysis of Biologic Disease-Modifying Antirheumatic Drugs for Patients With Psoriatic Arthritis in Thailand

ObjectivesThis study aimed to assess the cost-effectiveness of biologic disease-modifying antirheumatic drugs (bDMARDs) for treating patients with psoriatic arthritis who failed conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). MethodsA decision tree and Markov model were constructed to capture long-term costs and outcomes from a societal perspective. Patients with psoriatic arthritis who failed 2 previous csDMARDs were modeled over a 3-month cycle with a lifetime horizon. Clinical probabilities were derived from a published meta-analysis. Prices of bDMARDs were proposed by pharmaceutical companies. Other costs and utilities were based on data in Thailand. All costs and outcomes were discounted at a 3% annual rate. Incremental cost-effectiveness ratio and a series of sensitivity analyses were performed. ResultsAll 11 bDMARDs (3 infliximab originator and biosimilars, 2 etanercept originator and biosimilar, golimumab, 2 secukinumab 150 mg and 300 mg, 3 adalimumab biosimilars) gained better quality-adjusted life-years (QALYs) with more costly than csDMARDs. Infliximab had the highest QALYs compared with other bDMARDs. Only secukinumab 150 mg showed the incremental cost-effectiveness ratio below the Thai threshold of 5152 US dollars per QALY. Cost of bDMARDs was the most influential factor. ConclusionsAt the current price, secukinumab 150 mg shows the value for money in the Thai context. Price negotiation is of great importance for other bDMARDs.

Advanced assessment through intact glycopeptide analysis of Infliximab's biologics and biosimilar.

Characterization of therapeutic monoclonal antibodies (mAbs) represents a major challenge for analytical sciences due to their heterogeneity associated with post-translational modifications (PTMs). The protein glycosylation requires comprehensive identification, which could influence on the mAbs' structure and their function. Here, we demonstrated high-resolution tandem mass spectrometry with an ultra-high-performance liquid chromatography for characterization and comparison between biologics and biosimilar of infliximab at an advanced level. Comparing the N- and O-glycopeptides profiles, a total of 49 and 54 glycopeptides was identified for each product of the biologics and biosimilar, respectively. We also discovered one novel N-glycosylation site at the light chain from both biopharmaceuticals and one novel O-glycopeptide at the heavy chain from only biosimilar. Site-specific glycopeptide analysis process will be a robust and useful technique for evaluating therapeutic mAbs and complex glycoprotein products.

How do hospital characteristics and ties relate to the uptake of second-generation biosimilars? A longitudinal analysis of Portuguese NHS hospitals, 2015–2021

ABSTRACT Background There is limited evidence on within-country discrepancies in biosimilar uptake. This study analyzes differences in timing and diffusion of biosimilar uptake across Portuguese NHS hospitals and explores possible determinants. Research design and methods We analyzed publicly accessible consumption data of originator biologic and biosimilar drugs for adalimumab, etanercept, infliximab, rituximab, and trastuzumab, by hospital and month for the years 2015–2021 (N = 9,467). We modeled the time to biosimilar adoption using survival regression models and the share of biosimilar consumption using generalized estimated equations with random hospital effects. Results Academic hospitals were characterized by a quicker uptake of adalimumab and infliximab biosimilars but lower shares for other drugs. A higher total consumption of biologics was related to a lower share of biosimilar uptake. A stronger participation in randomized controlled trials was linked to higher biosimilar shares and quicker uptake, except for rituximab. If all NHS hospitals had biosimilar shares equal to the highest ones, potential annual savings could reach 13.9 million euros. Conclusion The findings suggest a need for capacity-building on biosimilar prescribing, including for doctors of academic hospitals and those working in settings where high biosimilar use would be expected.

Patient Out-of-Pocket Costs Following the Availability of Biosimilar Versions of Infliximab.

After market exclusivity ends for biologic drugs, biosimilars-follow-on versions made by other manufacturers-can compete with lower prices. Biosimilars have modestly reduced prescription drug spending for US payers, but it is unclear whether patients have directly experienced any savings. In this study we assessed whether availability of biosimilar infliximab was associated with lower out-of-pocket (OOP) costs, using claims from a national data set of commercially insured patients from 2014 to 2018. We used two-part models, adjusting for patient demographics, clinical characteristics, insurance plan type, and calendar month. Compared with the reference biologic, there was no difference in the percentage of biosimilar claims with OOP costs (30.1% vs. 30.8%; adjusted odds ratio (aOR) 0.98, 95% confidence interval (CI), 0.84-1.15, P=0.84) or the average nonzero OOP cost (median $378 vs. $538, adjusted mean ratio (aMR) 0.97, 95% CI, 0.80-1.18, P=0.77). The percentage of claims with OOP costs was lower after biosimilar competition (30.7% vs. 35.0%, aOR 0.96, 95% CI, 0.94-0.99, P=0.003), but average nonzero costs increased (median $534 vs. $520, aMR 1.04, 95% CI, 1.01-1.07, P=0.004). Thus, early biosimilar infliximab competition did not improve affordability for patients. Policymakers need to better assure that competition in the biosimilar market translates to lower costs for patients using these medications.

Efficacy of Infliximab Biosimilar for Maintenance Therapy in Pediatric Inflammatory Bowel Disease Following Infliximab Originator.

Single-center, retrospective chart review of 25 children with inflammatory bowel disease who transitioned from Remicade (IFX-O) to the biosimilar agent Inflectra (IFX-B) for maintenance therapy. Analysis included demographics and various biochemical markers of disease control. The nonparametric-related samples Wilcoxon signed-rank test was used to compare mean ranks of these markers (C-reactive protein, erythrocyte sedimentation rate, hemoglobin, platelet count, albumin, body mass index z score) between the last 12 months on IFX-O and the first 12 months on IFX-B. Between March 2018 and June 2018, the majority of patients with pediatric inflammatory bowel disease on maintenance therapy with IFX-O at our institution were transitioned to maintenance therapy with IFX-B. Of the 25 children included, 17 were diagnosed with Crohn disease and 8 with ulcerative colitis. The results of all, except albumin value, supported retention of the null hypothesis that there would not be a statistically significant difference in the biochemical markers of disease activity between the 2 medications. IFX-B is as effective as IFX-O for maintenance therapy in pediatric inflammatory bowel disease when comparing biochemical markers of disease activity.

Infliximab biosimilar-to-biosimilar switching in patients with inflammatory rheumatic disease: clinical outcomes in real-world patients from the DANBIO registry

ObjectiveSuccessful uptake of biosimilars in rheumatology is limited by lack of real-world evidence regarding effectiveness of biosimilar-to-biosimilar switching. We investigated infliximab biosimilars CT-P13-to-GP1111 switching among patients with rheumatoid arthritis (RA),...

Efficacy and safety of biosimilar versus originator infliximab in patients with inflammatory bowel disease: A real-world cohort analysis.

Anti-tumor necrosis factor (anti-TNF) monoclonal antibody, infliximab, is the primary therapeutic modality for patients with Crohn's disease (CD) and ulcerative colitis (UC), refractory to conventional therapy. Biosimilars of infliximab have been shown to have equivalent efficacy to originator infliximab. We compared the safety and efficacy of infliximab biosimilar with the originator in Indian patients with inflammatory bowel disease (IBD). Patients with IBD treated with either originator or biosimilar infliximab from January 2005 to October 2020 were included in this retrospective analysis. The safety and efficacy of originator or biosimilar infliximab in inducing and maintaining clinical remission at weeks 14 and 52 for CD and UC were evaluated. Disease activity was estimated at baseline, after induction therapy, after 1 year of treatment, and during 12 months of follow-up. In all, 137 patients (82 CD; 55 UC) were included, of whom 102 were on originator, and 35 patients received biosimilar. In biosimilar group, clinical response and remission rates at weeks 14 and 52 were 84.2%, 58% and 68.4%, 52.6% in CD and 81.2%, 56.2% and 68.7%, 62.5% in UC patients, respectively. Among patients who were on originator, clinical response and remission rates at weeks 14 and 52 were 79.4%, 46% and 57.1%, 43% in CD and 72%, 64.1% and 66.7%, 56.4% in UC patients, respectively. Thirty-three (24.1%) patients experienced adverse events; eighteen developed tuberculosis (TB), of whom 17 received originator and one patient received biosimilar. Infliximab biosimilar is comparable to originator infliximab in terms of safety profile and its efficacy in inducing and maintaining remission in patients with IBD.

Effectiveness and safety in the management of chronic inflammatory diseases with etanercept and infliximab biosimilars in Colombian patients

ObjectiveTo determine the effectiveness and safety of infliximab and etanercept biosimilar drugs in patients diagnosed with rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, and psoriasis in a specialized institution in Colombia, between 2015 and 2019. MethodsA retrospective study in patients treated with infliximab and etanercept biosimilar drugs treated in an institution specializing in the management of rheumatological diseases, to verify the clinimetric indicators of effectiveness and reports of adverse drug reactions. Clinical, sociodemographic, and pharmacological variables were identified over 5 years of follow-up. Results207 patients were identified with a mean age of 48.7±15.1 years, 61.4% were women. Of the patients, 58.0% (n=120) used infliximab and 42.0% (n=87) etanercept. It was found that 46 (22.2%) patients had adverse drug reactions. At the end of the observation period, 61.6% (n=72) of the patients with RA had achieved control of the disease (mild activity or remission), and 57.9% (n=117) had problems with access to and persistence with therapy. ConclusionIn a group of patients treated in Colombia, the biosimilars of infliximab and etanercept showed proportions of effectiveness and safety comparable to the reference drugs, but lack of adherence to treatment was quite common.

Patients with Ankylosing Spondylitis Can Maintain Clinical and Functional Improvement after Switching from Infliximab Reference Product to Infliximab Biosimilar (REMSIMA): 12 Months Comparative Open-Label Study

Objective: Efficacy, tolerance, and safety of infliximab biosimilar are the same as infliximab reference product (RP) in the management of ankylosing spondylitis (AS) patients previously were on infliximab RP. We aimed to evaluate the biosimilar CT-P13 (Remsima) in terms of efficacy, tolerance, and safety to its RP. Materials and methods: Seventy-eight consecutive randomly selected patients were recruited for the study. All patients were naïve to any other biologics before receiving infliximab RP, and all were in clinical remission. The sample of patients was divided into two subgroups: 40 patients were continued on infliximab RP and 38 patients were switched to infliximab biosimilar. All patients underwent clinical evaluation and investigation. Both groups followed up for further 12 months. The disease activity was calculated utilizing Ankylosing Spondylitis Disease Activity Score (ASDAS), using the C-reactive protein (CRP), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Remission considered when BASDAI < 4 and ASDAS < 1.3. Functional scores for all patients were assessed using the Bath Ankylosing Spondylitis Functional Index (BASFI). Results: Sustained clinical remission was observed after 12 months of treatment in the infliximab RP continued and switched groups. At the end of the study, erythrocyte sedimentation rate (ESR), CRP, visual analog scale (VAS), ASDAS, BASDAI, and BASFI were 15.04 ± 2.37, 2.10 ± 0.88, 3.10 ± 0.78, 1.52 ± 0.40, 2.80 ± 0.37, and 3.05 ± 0.24 in the infliximab RP continued group, respectively, and were 15.15 ± 1.45, 2.29 ± 0.89, 3.21 ± 0.69, 1.59 ± 0.57, 2.76 ± 0.45, and 2.89 ± 0.92 for the switching group, respectively; the difference was statistically not significant ([Formula: see text] values > 0.05). No significant adverse events were noted in the switching group compared to the continuous group groups. Conclusion: We found infliximab biosimilar CT-P13 (Remsima) was not inferior to infliximab RP and can maintain patients with ankylosing spondylitis in clinical remission.

Rapid infusion of infliximab biosimilars and the incidence and severity of infusion-related reactions in patients with inflammatory bowel disease.

Infliximab is an anti-tumour necrosis factor agent used in the treatment of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. While the use of infliximab is well established in the treatment of IBD, there are now four recently FDA-approved infliximab biosimilars that are increasingly used due to their cost-benefit for patients, institutions and payors. In addition, shortening the length of infliximab infusions from 120 min (standard infusion) to 60 min or less (rapid infusion) has been shown to safely provide further cost-benefit while also improving patient convenience. The safety of rapid infusions has been well-established for the infliximab reference product, however, there are limited data available regarding the safety of rapid infusions for infliximab biosimilars. The purpose of this study was to compare the incidence and severity of infusion reactions among patients with IBD receiving rapid infusion of infliximab reference product compared with infliximab biosimilar. This was a retrospective analysis of electronic health record data of patients with a diagnosis of IBD receiving an infliximab reference product or infliximab biosimilar infusion between December 2020 and December 2021. Patient-level variables included demographics, immunomodulator use, IBD-related hospitalization and infliximab trough concentration and antibody levels. Infusion-related variables of interest included total number of infusions, drug, dose, dosing interval, infusion time and use of pre-medications. Infusion-related reactions were defined as safety concerns documented by the administering nurse (anaphylaxis, shortness of breath, hypotension, swelling, rash, pruritus, hives, flushing, chest pain, muscle pain, joint pain, fevers, chills, headache or hypertension) or administration of emergency medications. Fisher's exact test was used to compare reaction rates. A total of 188 patients met inclusion criteria for analysis, and a total of 1124 infusions were administered during the study period. There were no statistically significant differences among any of the pre-specified outcomes. There were no differences in the incidence of infusion reactions among rapid infusion (60 min) infliximab and infliximab biosimilars (p=0.863). Additionally, there were no differences in the incidence of infusion reactions among standard infusion (120 min) infliximab and infliximab biosimilars (p=0.993). Finally, there were no differences among the rate of infusion reactions between rapid infusion of infliximab biosimilars and standard infusion of infliximab biosimilars (p=0.536). Eight patients experienced safety issues, with three patients requiring emergency medications (1.6% of 188 patients). Rapid infusions of infliximab biosimilars were not associated with an increase in the incidence of infusion reactions compared with: rapid infusion of infliximab reference product, standard infusion of infliximab biosimilars, or standard infusion of infliximab reference product. This should reassure clinicians that rapid infusions of infliximab biosimilars are safe in clinical practice.