Reference Infliximab Research Articles

Comparison of Reference and Biosimilar Medications for Pediatric Noninfectious Uveitis.

Compare outcomes and costs of TNF-alpha inhibitor biosimilars to reference medications in the treatment of pediatric NIU. Patients 18 years old or below treated with reference or biosimilar TNF-alpha inhibitor for noninfectious uveitis and had a history of active ocular inflammation with at least 1 month of ophthalmology follow-up from January 1, 2013, to June 1, 2023, were included. Retrospective chart review was performed. Nineteen patients met the inclusion criteria. Mean age was 9.3±4.0 years, and 47.4% (9/19) were female. Of the patients who were on infliximab at any time point in their disease course (n=9), the mean duration on infliximab was 3.6 years (42mo). Of the patients on biosimilar infliximab (n=10), the mean duration was 0.82 years (9.8mo). Mean flares/year was 0.22±0.3 on infliximab and 0.15±0.3 on biosimilar infliximab. The average annual cost was $42,298.97 for infliximab (n =9), $41,141 for infliximab-dyyb (n=9), and $40,950 for infliximab-axxq (n=1). Reasons for switching to biosimilar infliximab from adalimumab included a combination of insurance mandate (100%), worsening disease activity (37.5%), or other issues such as noncompliance (37.5%). The most common reason for biosimilar initiation was insurance mandate. Compared with the reference infliximab, pediatric patients had fewer number of flares per year on biosimilar infliximab, but they were also on the biosimilar for a shorter duration of time compared with the reference which may confound an accurate assessment. Biosimilar infliximab had a lower cost profile compared with reference infliximab.

Characteristics and 6-Month Outcomes in Patients with Rheumatoid Arthritis Initiating Infliximab Biosimilar IFX-dyyb in a Real-World Setting.

Real-world studies describing biosimilar initiation or switching in patients with rheumatoid arthritis (RA) are limited. The aim of this study was to assess treatment patterns and effectiveness of real-world patients with RA initiating infliximab biosimilar IFX-dyyb (CT-P13; Inflectra®) in the USA. This observational study evaluated patients with RA from the CorEvitas RA Registry who initiated IFX-dyyb and had Clinical Disease Activity Index (CDAI) recorded at baseline and 6months. The primary outcome was reaching low disease activity (LDA; CDAI ≤ 10) at 6months in patients with moderate or high disease activity (CDAI > 10) at baseline. Secondary outcomes were change at 6months in CDAI and certain patient-reported outcomes (PROs). Patient data were stratified by prior treatment: biologic/targeted synthetic disease-modifying antirheumatic drug (tsDMARD)-naïve, reference infliximab (IFX-REF) or IFX biosimilar, or a non-IFX biologic or tsDMARD. Of 318 patients initiating IFX-dyyb, 176 had baseline and 6-month CDAI scores; 73 (41%) switched from IFX, 61 (35%) switched from another non-IFX/biologic/tsDMARD, 32 (18%) were naïve to biologics/tsDMARDs, and 10 (6%) switched from an IFX biosimilar. Among patients with moderate or high disease activity at baseline, 32.9% (95%CI 22.9, 42.9) achieved LDA at 6months. Mean 6-month change from baseline in CDAI was - 1.8 (95%CI - 3.3, - 0.3) overall; - 4.7 (- 7.6, - 1.7) in patients who switched from a non-IFX biologic/tsDMARD, - 4.1 (- 7.8, - 0.3) in biologic/tsDMARD-naïve patients, and 1.1 (- 0.4, 2.6) in patients who switched from IFX-REF/IFX biosimilar. Other clinical outcomes/PROs improved at 6months. Of the IFX-dyyb initiators, 68% remained on IFX-dyyb at 6months. In this real-world population of patients with RA initiating IFX-dyyb, the majority switched from IFX-REF or a non-IFX biologic/tsDMARD. CDAI remained stable in patients switching from IFX-REF/IFX biosimilar and improved in patients switching from a non-IFX biologic/tsDMARD and in biologic/tsDMARD-naïve patients.

Evaluation of selected serum biomarkers levels in response to the infliximab reference product (Remicade®) versus its biosimilar (Remsima®) in a sample of ulcerative colitis patients: a cross-sectional study

Background: Biologic therapies like Remicade® (infliximab originator) and Remsima® (infliximab biosimilar) have emerged as valuable options for the management of ulcerative colitis (UC) over the years. The purpose of the present study was to provide comprehensive comparison of the efficacy of Remicade® and Remsima® in the treatment of UC by performing a comprehensive analysis of key biomarkers. Methods: The study utilized a cross-sectional observational design. It was conducted at Baghdad Teaching Hospital in Baghdad, Iraq, spanning from July 2022 to February 2023. The study population consisted of individuals aged 21 to 57 years who had previously received a diagnosis of ulcerative colitis (UC). Results: A total of 43 patients were included in the analysis. The mean infliximab trough levels in the Remicade group were 3.264 ng/mL, while in the Remsima group were 3.248 ng/mL. eight Remicade patients developed anti-infliximab antibodies, while 9 Remsima patients tested positive. The mean serum calprotectin level was 5596 μg/ml in the Remicade group and 5795μg/ml in the Remsima group. The mean ESR value was 18.33mm/hr in the Remicade group and 16.43mm/hr in the Remsima group. The mean CRP value was 17.65mg/dl in the Remicade group and 16.19mg/dl in the Remsima group. The mean serum TNFa level measured was 159.5pg/ml in the Remicade group and 158.5pg/ml in the Remsima group. The mean serum Oncostatin M level measured was 107.3ng/ml in the Remicade group and 107.5ng/ml in the Remsima group Conclusion: These findings study suggest that Remsima, as a biosimilar to Remicade, holds promise as a cost-effective alternative in UC management

Comparative effectiveness and drug survival of biosimilar infliximab CPT-13 vs. reference infliximab in inflammatory bowel disease: A retrospective cohort study

BackgroundStudies have investigated the efficacy and safety of switching to the biosimilar infliximab (CT-P13) in patients with inflammatory bowel disease (IBD). However, there is limited research directly comparing the effectiveness, drug survival, and pharmacokinetic profiles of the reference infliximab (IFX) and CT-P13 in real clinical settings. ObjectiveTo compare the effectiveness and drug survival of CPT-13 and reference IFX at weeks 26 and 52, and to determine the pharmacokinetic profiles and safety profile in real-world settings. MethodsA retrospective observational cohort analysis was conducted at a single center. The study compared the proportion of patients achieving clinical remission and experiencing poor clinical outcomes at weeks 26 and 52. The drug survival rate of CT-P13 and reference infliximab was also assessed during the follow-up period. ResultsA total of 153 patients were included in the study, 39.2% receiving CPT-13 and 60.8% reference IFX. At week 26, clinical remission rates were 66.7% (CPT-13: 74.4% vs. reference IFX: 62.3%, p=0.178), and at week 52, they were 64% (CPT-13: 85.4% vs. reference IFX: 63.0%, p=0.012). Subgroup analysis with therapeutic drug monitoring (TDM) found no significant differences at week 26 (CPT-13: 74.4% vs. reference IFX: 58.8%, p=0.235) or at week 52 (CPT-13: 85.4% vs. reference IFX: 68.8%, p=0.153). ConclusionOur study demonstrates comparable efficacy, drug survival, pharmacokinetic profiles, and incidence of immunogenicity between both drugs in a real clinical setting. Further studies with greater statistical power are needed to validate these findings.

EPH93 Traceability of Infliximab Reference Medicinal Product and Its Biosimilar Products Adverse Drug Events Reports in Saudi Arabia

Infliximab reference product and two biosimilar products were approved by the Saudi Food & Drug Authority (SFDA) for the treatment of a wide variety of inflammatory conditions such as rheumatoid arthritis, Crohn's disease, and ankylosing spondylitis. Recording both the product trade name and the batch number are essential in the spontaneous reporting of adverse drug events (ADEs) of biological medicines due to the variability of the bio-manufacturing process that may cause safety risks such as immunogenicity. This study aims to assess the availability of batch number and trade name in the ADE reports of Infliximab (reference product) and biosimilar products in the National Pharmacovigilance Center (NPC) database at SFDA.

Validation Study of Novel Point-of-Care Tests for Infliximab, Adalimumab and C-Reactive Protein in Capillary Blood and Calprotectin in Faeces in an Ambulatory Inflammatory Bowel Disease Care Setting.

Background and aims: Point-of-care tests (POCT) allow instant measurement of inflammatory markers and drug concentrations. Here, we studied agreement between a novel POCT device and reference methods of measuring infliximab (IFX) and adalimumab (ADL) serum concentrations and C-reactive protein (CRP) and faecal calprotectin (FCP) concentrations of patients with inflammatory bowel disease (IBD). Methods: In this single-centre validation study, IBD patients were recruited in which IFX, ADL, CRP and/or FCP tests were required. IFX, ADL and CRP POCT were performed on capillary whole blood (CWB), obtained via finger prick. Additionally, IFX POCT was performed on serum samples. FCP POCT was performed on stool samples. Agreement between POCT and reference methods was tested using Passing-Bablok regression, intra-class correlation coefficients (ICC) and Bland-Altman plots. Results: In total, 285 patients participated. Passing-Bablok regression identified differences between the reference method and IFX CWB POCT (intercept = 1.56), IFX serum POCT (intercept = 0.71, slope = 1.10) and ADL CWB POCT (intercept = 1.44). There were also differences in the Passing-Bablok regressions of CRP (intercept = 0.81, slope = 0.78) and FCP (intercept = 51 and slope = 0.46). Bland-Altman plots demonstrated that IFX and ADL concentrations were slightly higher with the POCT and CRP and FCP were slightly lower with POCT. The ICC demonstrated almost perfect agreement with IFX CWB POCT (ICC = 0.85), IFX serum POCT (ICC = 0.96), ADL CWB POCT (ICC = 0.82) and CRP CWB POCT (ICC = 0.91) and moderate agreement with FCP POCT (ICC = 0.55). Conclusions: IFX and ADL results were slightly higher with this novel rapid and user-friendly POCT, whereas CRP and FCP results were slightly lower compared to the reference methods.

Comparison between Reference Infliximab (Remicade) and its Biosimilar (Remsima) in Patients with Ankylosing Spondylitis: A Field-based Pharmacoeconomic Study

Background: Ankylosing spondylitis is a chronic inflammatory disease that mostly involves the spine and sacroiliac joints. It is associated with a decreased quality of life. Biological medicines such as infliximab and its biosimilar are the mainstay treatments for active ankylosing spondylitis. Objective: The study objective was to conduct a pharmacoeconomic study comparing the cost-effectiveness of the reference infliximab with its biosimilar in ankylosing spondylitis patients visiting public hospitals. Subjects and Method: This is a two-center pharmacoeconomic study performed at two large teaching governmental hospitals in Baghdad, Iraq, which supplied infliximab to outpatients with ankylosing spondylitis. The outcome data were obtained from patient’s medical records and face-to-face interviews with the patients from December 2021 through April 2022. The Independent T-Test was used to measure the differences in areas of utility, and quality of life, between the two infliximab groups. Results: The study recruited 62 patients with ankylosing spondylitis who received infliximab (31 received Remicade, and 31 received Remsima) for at least 12 weeks at two public teaching hospitals. The mean age of the patients was 37.85 years and 83.9% were men. In general, both reference infliximab and its biosimilar were successful in increasing the quality of life. Their importation costs were different from 2019 to 2021. The incremental cost-effectiveness ratio of reference infliximab versus biosimilar was $ 40,909/quality-adjusted life year (QALY) according to 2019 pricing. In contrast, in 2021 reference infliximab (Remicade) was less expensive and yielded slightly better quality of life improvement than biosimilar (Remsima) making Remicade more cost-effective (dominant). Conclusion: Remicade was slightly superior to Remsima in quality of life improvement. However, it was difficult to determine whether the reference or its biosimilar was more cost-effective in 2019 because the health officials did not specify a willingness to pay per quality-adjusted life year. Compared to Remsima, Remicade was more cost-effective in 2021 because it was less expensive and more effective in terms of quality of life improvement.

Real-world observational cohort study of treatment patterns and safety outcomes of infliximab biosimilar CT-P13 for the treatment of inflammatory bowel disease (CONNECT-IBD)

ABSTRACT Background The objective of this non-interventional, observational prospective cohort study (CONNECT-IBD) was to assess the use of CT-P13 (Inflectra®) in the treatment of patients with Crohn’s disease (CD) and ulcerative colitis (UC) in the context of treatment with reference infliximab (IFX; Remicade®). Methods Patients (recruited April 2015 to October 2018) at 150 sites across 13 European countries were followed for up to 2 years. Primary outcomes were safety, population characteristics, and drug utilization patterns. Secondary outcomes included clinical assessment of disease activity. Data were analyzed descriptively. Results Overall, 2543 patients (CD, n = 1676; UC, n = 867) were included. In the CT-P13 cohort (n = 1522), median disease duration was 63 (0–579) months and 30% of patients were IFX naïve; median duration of prior IFX treatment was 5 months. During the observation period, median duration of drug exposure was 14 (0–28) months. 41% of patients reported 912 all-causality treatment-emergent adverse events (TEAEs); 24% experienced treatment-related TEAEs. Most TEAEs were of mild-to-moderate severity. Treatment-emergent serious adverse events were reported by 17% of patients. Conclusion Safety information for CT-P13 in this large study was consistent with the known safety profile for IFX and did not alter the established benefit-risk profile of CT-P13.

Real-world evidence of the use of the infliximab biosimilar SB2: data from the PERFUSE study.

PERFUSE is a non-interventional study of 1233 adult patients (rheumatology, n = 496; IBD, n = 737) receiving routine infliximab (IFX) biosimilar SB2 therapy. The aim of this report was to investigate the 12-month persistence, effectiveness and safety outcomes of routine SB2 treatment in patients with chronic inflammatory rheumatic disease. Patients with a diagnosis of RA, PsA or axial spondyloarthritis (axSpA) were assigned to one of three study cohorts according to whether SB2 treatment initiated after September 2017 had been the first IFX treatment (IFX naïve) or followed transition from reference IFX (IFX ref) or another IFX biosimilar (IFX bs). Outcomes to month 12 (±2) included persistence (primary outcome), SB2 dose, disease status, immunogenicity and safety. At month 12, persistence on SB2 in IFX-naïve, IFX ref and IFX bs cohorts, respectively, [mean percentage (95% CI)] by indication was as follows: 59% (36.1, 76.2), 75% (57.5, 86.1) and 85% (69.6, 93.0) for RA (n = 98); 64% (34.3, 83.3), 87% (65.6, 95.7) and 83% (60.0, 93.1) for PsA (n = 62); and 56% (44.4, 66.5), 80% (70.8, 86.1) and 80% (72.5, 85.6) for axSpA (n = 336). Disease activity was comparable at baseline and month 12 within the IFX ref and bs subgroups of all cohorts by indication. No immunogenicity concerns or new safety signals were detected. SB2 was safe and effective in IFX-naïve patients and in patients transitioned from prior IFX ref or bs. clinicaltrials.gov, NCT03662919.

Cost-effectiveness Analysis of Reference Infliximab (Remicade) Compared to its Biosimilar (Remsima) in Iraqi Patients with Rheumatoid Arthritis (Conference Paper )#

The study objective was to conduct Pharmacoeconomics study (cost-effective analysis) between infliximab reference (Remicade) and its biosimilar (Remsima) in patients with rheumatoid arthritis (RA) in Iraqi hospitals.
 This is a retrospective multicenter pharmacoeconomic analysis conducted at two large teaching governmental hospitals in Baghdad, Iraq which provided infliximab to patients with RA. Data were collected from patient’s medical records and face-to-face interviews with the patients from December 2021 to April 2022.
 The study included 57 patients with rheumatoid arthritis (RA). The patients were categorized into two groups according to the type of infliximab they received over 30 weeks: 27 patients received reference infliximab (Remicade) and 30 patients received biosimilar infliximab (Remsima). The two groups had comparable demographic and baseline disease parameters, with a mean age of 49.6 years and a BMI of 30.0. The vast majority of participants were women (82.5%) with low level of formal education (65%). Overall, both infliximab biopharmaceuticals had good effectiveness to reduce the RA disease activity (CDAI) and improve patient quality of life. They both had comparable adverse reactions including UTI, fatigue, and headache. There was no significant difference (P-value >0.05) in disease activity between the two groups according to RA clinical disease activity index (CDAI) score across all three-time measures: before biological therapy, 14 weeks post-therapy and 30 weeks post-therapy.
 In 2019, Remicade was slightly more effective and provide better quality of life, but costlier ($41,896 per QALY) compared to Remsima. It was not clear whether the reference biologic (Remicade) or its biosimilar (Remsima) was more cost effective. In 2021, Remicade was more cost effective compared to Remsima because Remicade was less expensive and relatively more effective according to CDAI and EQ-5D-5L scores. Registering and purchasing both reference infliximab and its biosimilar was good idea to keep the competition in the price and maintain infliximab for RA patients.

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.

PERFUSE: a French non-interventional study of patients with inflammatory bowel disease receiving infliximab biosimilar SB2: a 12-month analysis

FlixabiTM (SB2) is a biosimilar of the reference infliximab (IFX), Remicade®. Published evidence on long-term, real-world use of SB2 in patients either IFX naive or transitioned from prior IFX is scarce. We evaluated persistence, effectiveness, and safety of SB2 over 12 months in adults with IBD [Crohn's disease (CD) and ulcerative colitis (UC)], participating in PERFUSE. PERFUSE is a long-term, non-interventional, multicenter study of patients receiving SB2 at specialist sites across France. SB2 treatment was initiated in September 2017, either as first IFX treatment (IFX naive), after transition from treatment with reference IFX (IFX ref) or another IFX biosimilar (IFX bs), or both IFX ref and IFX bs (IFX multiswitch). Outcomes up to Month 12 (±2) include persistence on SB2 (primary outcome measure), SB2 dose, disease status, immunogenicity, and safety. This final 12-month analysis of patients with IBD includes 569 with CD and 168 with UC. Persistence [95% confidence interval (CI)] at Month 12 was CD: 89% (77.2; 94.9), UC: 78.5% (58.2; 89.8) for IFX naive; CD: 94% (91.0; 96.1), UC: 92.8% (84.8; 96.7) for IFX ref; CD: 91.6% (86.0; 95.0), UC: 94.2% (83.1; 98.1) for IFX bs; and CD 100% (100; 100), UC 100% (100; 100) for IFX multiswitch. In the CD and UC cohorts, disease activity among IFX naive patients declined from baseline to Month 12; with any prior IFX, the proportions of patients in remission at baseline, Month 6, and Month 12 remained unchanged in the UC cohort, and were comparable or higher in the CD cohort. No immunogenicity or safety signals were detected. Patients with IBD can be initiated on SB2 or transitioned from IFX ref and/or IFX bs to SB2, with no loss of disease control or safety concerns, with >75% of naive and >90% of transitioned patients continuing on SB2 treatment at 12 months.

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.

Use of multibiomarker disease activity scores in biosimilarity studies for the treatment of patients with rheumatoid arthritis

ObjectivesThis exploratory analysis investigated the potential use of the multibiomarker disease activity (MBDA) score to support biosimilarity assessments using data from two randomised controlled trials (RCTs) of biosimilar infliximab (IFX-qbtx)...

Fine Comparison of the Efficacy and Safety Between GB242 and Infliximab in Patients with Rheumatoid Arthritis: A Phase III Study

IntroductionThis phase III trial (NCT04178850) evaluated the efficacy, safety, and immunogenicity of GB242, an infliximab biosimilar, vs. infliximab (Remicade®) reference product in patients with moderate-to-severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy.MethodsPatients were randomized in a 1:1 ratio to receive either GB242 or INF (3 mg/kg). Therapeutic equivalence of clinical response according to the American College of Rheumatology 20% (ACR20) response rate at week 30 was declared if the two-sided 95% CI for the treatment difference was within ± 14%. The comparison of GB242 with INF also included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity.ResultsA total of 570 subjects were randomized into GB242 (N = 285) or INF (N = 285) and 283 subjects in each group were analyzed. At week 30, the ACR20 was 62.54% for the GB242 group (95% CI 56.62–68.20%) and 56.89% for the INF group (95% CI 50.90–62.74%). The difference between the two groups was 5.65% with a 95% CI of – 2.48 to 13.74. ACR50 response was 37.12% for GB242 and 32.86% for INF at week 30. ACR70 response was 19.79% for GB242 and 16.96% for INF at week 30, respectively. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs. 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs. 59.4% in INF) was comparable.ConclusionsGB242 demonstrated equivalent efficacy to INF at week 30. Moreover, GB242 was well tolerated, with a similar immunogenicity and safety profile comparable to INF.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00396-8.

Subcutaneous Infliximab, CT-P13SC: A Profile of Its Use in the EU.

CT-P13 (Remsima®; Inflectra®), a biosimilar of reference infliximab (Remicade®), provides a useful alternative for patients requiring infliximab therapy and, as with other biosimilar agents, has the potential to reduce treatment costs. Furthermore, the availability of CT-P13 in a subcutaneous formulation (CT-P13SC), with the possibility (after adequate training) of self-administration at home, has the potential to both improve patient convenience and reduce the burden on the healthcare system. The initial approval of CT-P13SC, for use in the treatment of rheumatoid arthritis in adults, was based on the findings of a randomised, double-blind phase I/III trial which demonstrated the non-inferiority of CT-P13SC administered once every 2weeks to intravenous CT-P13 (CT-P13IV) administered once every 8weeks in reducing disease activity in patients with active rheumatoid arthritis. Subsequently, based on pharmacokinetic data in patients with inflammatory bowel disease, CT-P13SC has also been approved in the EU for use in the treatment of Crohn's disease, ulcerative colitis and, by extrapolation, ankylosing spondylitis, psoriatic arthritis and psoriasis, in adults.

Biosimilar infliximab CPT-13 for inflammatory bowel disease in a real clinical setting: pharmacokinetic outcomes, immunogenicity, and drug survival.

efficacy and safety were evaluated after switching to a biosimilar infliximab (CPT-13) in patients with inflammatory bowel disease (IBD). However, few cohort studies compare the pharmacokinetic profiles, immunogenicity, and safety of the reference infliximab (IFX) and CPT-13 in a real clinical setting. to compare the pharmacokinetic profiles and drug survival on the long term of reference IFX and CPT-13 at weeks 54 and 104. A secondary objective was to determine the long-term immunogenicity and safety profile of CPT-13 in patients with IBD in a real clinical setting. a retrospective, observational cohort analysis was performed in a single center, including patients with IBD under treatment with reference IFX or CPT-13. Serum drug concentrations were compared to determine if there were any significant differences in pharmacokinetic outcomes between reference IFX and CPT-13 at 26, 54, 78, and 104 weeks. The drug survival of reference IFX and CPT-13 was determined at weeks 54 and 104. one hundred and six patients were included during the study period. Forty-five (42.5 %) patients received CPT-13 and 61 (57.5 %) received reference IFX. A total of 347 serum samples were analyzed and no significant differences were observed between reference IFX and CPT-13. The percentage of patients who achieved serum concentrations within the target therapeutic range was similar in both groups (74.1 % for reference IFX and 72.5 % for CPT-13, p = 0.741). At week 54, withdrawal rates for reference IFX and CPT-13 were 11.5 % and 20.0 %, respectively (p = 0.226), whereas at week 104 they were 26.2 % and 28.9 %, respectively (p = 0.761). the pharmacokinetic characteristics and incidence of immunogenicity of CPT-13 in a real clinical setting are comparable to those of the infliximab originator. The two products also have similar long-term drug survival and the same safety profile.

Impact of Infliximab Biosimilar CT-P13 Dose and Infusion Interval on Real-World Drug Survival and Effectiveness in Patients with Ankylosing Spondylitis.

CT-P13 is an infliximab biosimilar approved for indications including ankylosing spondylitis (AS); the approved maintenance regimen is 5 mg/kg infused every 6–8 weeks. In clinical practice, modifications to infliximab dose and/or infusion interval can be beneficial to the patient. For CT-P13, real-world data on dose and/or interval adjustment are lacking. This analysis investigated the impact of such treatment pattern changes on effectiveness and drug survival up to five years for adult (≥18 years old) patients with AS in the Korean, real-world, retrospective rheumatoid arthritis and ankylosing spondylitis (RAAS) study. Overall, 337 patients with AS were identified: 219 who initiated infliximab treatment with CT-P13 (‘naïve’) and 118 who switched from reference infliximab to CT-P13 (‘switched’). Overall, 18/235 (7.7%), 110/224 (49.1%), and 101/186 (54.3%) evaluable patients had dose, infusion interval, or combined treatment pattern changes, respectively. More naïve (61.0%) versus switched (42.6%) patients had treatment pattern changes. Overall, Bath Ankylosing Spondylitis Disease Activity Index scores decreased from baseline to week 54, then remained stable; improvements were greater for patients with than without treatment pattern changes. Drug survival did not differ significantly between patients with or without treatment pattern changes. Findings suggest that adjusting dose and/or infusion interval can improve clinical outcomes for CT-P13-treated patients with AS.

Infliximab Biosimilar CT-P13 Observational Studies for Rheumatoid Arthritis, Inflammatory Bowel Diseases, and Ankylosing Spondylitis: Pooled Analysis of Long-Term Safety and Effectiveness.

Long-term, real-world safety and effectiveness data are required to support biosimilar use. This analysis pooled 5-year findings from observational studies of infliximab biosimilar CT-P13 treatment in patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and ankylosing spondylitis (AS). Patients enrolled in the CT-P13 4.2, 4.3, or 4.4 Korea/European Union registries were analysed if they had initiated infliximab treatment with CT-P13 (CT-P13 group) or had switched from reference infliximab to CT-P13 (switched to CT-P13 group). The primary objective was to investigate long-term safety by evaluating adverse events of special interest (AESIs) per the CT-P13 risk-management plan. Incidence rates per 100 patient-years (PYs) were calculated. Additional long-term safety endpoints, immunogenicity (assessments optional), and effectiveness were evaluated. Overall, 736 patients (642 CT-P13; 94 switched to CT-P13) were analysed. Median (range) exposure to CT-P13 was 19.433 (0.03-63.11) months overall. The incidence of treatment-emergent adverse events was 69.0% (CT-P13 group) and 60.6% (switched to CT-P13 group). Infusion-related reaction/hypersensitivity/anaphylactic reaction was the most frequent AESI overall, with an incidence of 4.3828 per 100 PY (95% confidence interval: 3.3603-5.6185). For most AESIs, incidence rates per 100 PY were broadly comparable between treatment groups, considering overlapping 95% confidence intervals. At baseline, 42/445 (9.4%) and 21/59 (35.6%) evaluable patients in the CT-P13 and switched to CT-P13 groups, respectively, were antidrug antibody (ADA)-positive. After CT-P13 treatment during the study, 188/425 (44.2%) evaluable patients had≥1 ADA-positive result, including 147/425 (34.6%) patients with negative or no ADA results reported at baseline. Effectiveness tended to increase over time for all indications. The analysis did not identify any new safety findings for patients with RA, IBD, and AS treated with CT-P13 for up to 5years in those who were infliximab-naïve at CT-P13 initiation, or those who had switched from reference infliximab to CT-P13. ClinicalTrials.gov identifiers: NCT02557295 (CT-P13 4.2; retrospectively registered on 23 September 2015); NCT02326155 (CT-P13 4.3; retrospectively registered on 25 December 2014); NCT02557308 (CT-P13 4.4; retrospectively registered on 23 September 2015).