Use Of CT-P13 Research Articles

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.

P529 Year-two follow-up results of an observational study conducted in Crohn’s disease and ulcerative colitis patients treated with infliximab biosimilar CT-P13 in a real-life setting

Abstract Background ReFLECT study has been carried out to investigate real life use of CT-P13, the first monoclonal antibody biosimilar to infliximab (IFX) originator. Aims: describe the profile of inflammatory bowel disease (IBD) patients (pts) treated with CT-P13 in a real-world setting and the treatment durability over time. Methods ReFLECT is a multicentre, prospective, observational study conducted in France. Eligible pts were IFX naive pts (IFX-N) starting CT-P13 and those who have been switched from infliximab originator to CT-P13 (IFX-S). Treatment maintenance was described indirectly and expressed as the percentage of pts without treatment failure during the 2 years of follow-up; treatment failure was defined as a permanent discontinuation of CT-P13 due to lack or loss of response and/or intolerance or death. Two years of follow-up final results of adult IBD pts using descriptive statistical analyses, are presented here. Results Among the 1400 adult pts included from Oct 2016 to April 2019, 751 had an IBD and 649 had a rheumatic disease; 530 pts with Crohn’s disease (CD; 51.5% females; mean age±SD: 38.1±13.9 years old; 327 IFX-N / 188 IFX-S) and 221 with ulcerative colitis (UC; 44.8% females; 43.5±17.3 years old; 152 IFX-N / 59 IFX-S), with a median disease duration since diagnosis of 7.5 and 6.2 years respectively. Nearly 80% of pts were already under CT-P13 before inclusion, and 35.3% of CD and 32.6% of UC pts had a concomitant treatment with AZA. At first CT-P13 administration, 54.3% of CD pts had an HBI>4 and 60.6% of UC pts had a Mayo score>6 in IFX-N pts compared with, 15.8% and 23.1% in IFX-S pts respectively. From first administration of CT-P13 to 24 months of follow-up, a higher proportion of pts without treatment failure was observed in IFX-S than in IFX-N pts: 83.7% [95%CI:78.0;89.9] vs 65.7% [58.6;73.7] in CD and 91.2% [81.7;100.0] vs 53.4% [43.0;66.2] in UC pts respectively (Figures 1 and 2). Main reason for CT-P13 withdrawing was treatment failure in IFX-N and IFX-S: 14.7% and 7.4% of CD, 21.7% and 5.1% of UC pts respectively. Withdrawing for intolerance involved 9.2% and 7.4% of CD, 7.2% and 3.4% of UC naive and switched pts respectively. Regarding safety (Table 1), 51.3% CD pts and 45.2% UC pts reported at least one adverse event (AE). AEs with suspected relationship with CT-P13 were described in 18.5% and 17.6% and serious AEs in 13.2% and 12.7% of CD and UC pts respectively. AEs were balanced between IFX-N and IFX-S. Conclusion 2 year follow-up data indicate that CT-P13 induce effective therapeutic maintenance in pts with CD and UC receiving IFX for the first time, and maintain a sustained disease control in pts having switched from IFX originator to CT-P13. This real-life study did not highlight any new safety concerns.

P289 A French nationwide prospective study on patients with Crohn’s disease and ulcerative colitis treated with Infliximab-biosimilar CT-P13 in a real-life setting: two-year follow-up of the ReFLECT study

Abstract Background ReFLECT study was carried out to investigate real-life use of CT-P13, the first monoclonal antibody biosimilar to infliximab (IFX) originator. Methods This multicentre, prospective, observational study was conducted in France to assess characteristics of patients (pts) receiving CT-P13, its effectiveness and safety in a real-life setting. Eligible were both pts who had been switched from IFX originator (IFXS) and IFX-naïve pts started on CT-P13 (IFXN). These interim descriptive statistical analyses are about pts with Crohn’s disease (CD) and ulcerative colitis (UC). Results Among the 1370 adult pts included between October 2016 and April 2019, data were analysed for 508 CD pts (48.6% males; mean age ± SD: 37.7±13.7; median [Q1;Q3] disease duration: 6.2 [1.9;13.7] years; 323 IFXN/145 IFXS) and 213 UC pts (54%; 42.9±17.2; 5.4 [1.6;12.8]; 154 IFXN/46 IFXS). Previous biologics other than IFX were taken by 32.9% of CD and 39.0% of UC pts; 31% (CDS) and 23% (UCS) of pts were switched from IFX originator to CT-P13. At the time of the first administration of CT-P13, disease had been more active in IFXN vs IFXS pts: 52.9% vs 13.3% in CD with a median [Q1;Q3] Harvey Bradshaw Index (HBI) of 4 [1;8] vs 1 [0;2] and, 82.9% vs 33.3% in UC with a median Mayo Score of 7 [3;10] vs 2 [0;4]. In IFXS pts, disease activity remained stable after 2 years of treatment with median differences of HBI and Mayo score since first administration of 1 [0;2] and 0 [-4;1]. In IFXN pts, median differences of HBI and Mayo score since first administration were -2 [-7;1] and -7 [-8;-5]; CT-P13 brought disease activity down to levels below or comparable to those seen in IFXS pts. Reasons for CT-P13 withdrawing and safety data are reported in Tables 1 and 2. Conclusion Year 2 follow-up data indicate that CT-P13 effectively induced improvement in disease activity in IFXN pts with CD or UC and maintained stable activity in IFXS pts. This real-life study did not highlight any new safety concerns.

Retention Rate and Efficacy of the Biosimilar CT-P13 Versus Reference Infliximab in Patients with Ankylosing Spondylitis: A Propensity Score-Matched Analysis from the Korean College of Rheumatology Biologics Registry.

BackgroundLong-term, real-world data are required to support the use of CT-P13 in chronic conditions such as ankylosing spondylitis. However, real-world evidence may be influenced by selection bias, which can confound outcomes. The aim of the current analysis was to confirm the long-term comparability of CT-P13 and reference infliximab treatment in patients with ankylosing spondylitis, using propensity score matching to adjust for baseline differences between groups.MethodsA propensity score–matching analysis was conducted on data from patients with ankylosing spondylitis in the Korean College of Rheumatology Biologics registry who received CT-P13 or reference infliximab. Drug retention, reasons for biologic therapy changes or discontinuation, and efficacy parameters were analyzed overall and by treatment line with up to 4 years of follow-up. Adverse events were recorded for each treatment group.ResultsPropensity score matching was effective in matching 124 CT-P13–treated and 124 reference infliximab-treated patients. Median treatment duration and drug retention were similar between CT-P13 and reference infliximab. Three-year retention rates (95% confidence interval [CI]) were 64.2% (53.5–73.0) for CT-P13 and 55.6% (42.9–66.6) for reference infliximab. Overall, 17.1% (CT-P13) and 29.3% (reference infliximab) of patients discontinued biologic therapy, and 20.0% (CT-P13) and 15.2% (reference infliximab) changed biologic therapy. Efficacy assessments were generally similar between groups; both treatments were well tolerated.ConclusionsPropensity score–matching analysis confirmed that CT-P13 treatment was not associated with significant differences in drug retention, treatment duration, most efficacy parameters, or safety versus reference infliximab in Korean patients with ankylosing spondylitis, building evidence for the long-term comparability of these treatments.Trial registrationClinicalTrials.gov identifier: NCT01965132.Electronic supplementary materialThe online version of this article (10.1007/s40259-020-00432-z) contains supplementary material, which is available to authorized users.

Anti-TNF Biosimilars in Inflammatory Bowel Disease: Searching the Proper Patient's Profile.

Biosimilars of infliximab (CT-P13) are currently approved and available for the same indications as for the originator. Some concerns about safety and immunogenicity have risen in the past because of lack of data in IBD. Since 2015, several cohort studies have been conducted in IBD showing that CT-P13 has comparable safety and efficacy profile to the originator, both in adult and pediatric population, either in naïve patients or even in those who switched from the originator to CT-P13. This review aims to analyze the current literature data in order to define a clear patient profile, to identify those IBD patients who would benefit the most from the use of CT-P13.

The Experience with Biosimilars of Infliximab in Rheumatic Diseases.

Infliximab biosimilars are the first biosimilars of monoclonal antibodies approved by the main regulatory agencies. Up to the present day, two infliximab biosimilars have been approved: CT-P13 (Celltrion), and SB2 (Biogen), but other companies have been developing candidate infliximab biosimilars that are on clinical trials: PF 06438179 (Pfizer), the ABP710 (bioCentury/Amgen) the BCD055 (JSC Biocad Russica) and BOW015 (Epirus). We have made a literature search in MedLine database using the key words [Infliximab] and [biosimilars] and [rheumatic diseases] and [rheumatisms]. We have also made a search in the clinicaltrials.org website. Clinical data published so far have provided important evidence on long-term efficacy and safety, immunogenicity and switching, supporting the use of CT-P13 and SB2 for the treatment of rheumatic diseases. In addition, the European experience has proved the economic advantages of the incorporation of infliximab biosimilars in clinical practice. Despite the widespread use of infliximab biosimilars there is still a lack of data regarding interchangeability between reference products and biosimilars.

CT-P13: design, development, and place in therapy.

The introduction of biological agents has revolutionized the management of many life-threatening and debilitating immune-mediated diseases. Because of the high cost of biological drugs and their patent expiration, the market has opened to biosimilar agents, copy versions of the originators, which can lead to reduced health care expenditure and increase treatment access worldwide. CT-P13 is the first biosimilar of infliximab (IFX) and has been approved for the same indications as its originator drug. It obtained regulatory approval by the European Medicines Agency in September 2013 and by the US Food and Drug Administration in April 2016. The Phase I and Phase III clinical trials conducted in ankylosing spondylitis and rheumatoid arthritis have demonstrated pharmacokinetic and efficacy equivalence with comparable safety and immunogenicity to IFX. For these reasons, the use of CT-P13 has been extrapolated also to inflammatory bowel disease. There have been some initial concerns regarding the use of CT-P13 in inflammatory bowel disease patients, because of the lack of randomized controlled trials. However, emerging real-world data have further confirmed the comparability between CT-P13 and its reference product in terms of efficacy, safety, and immunogenicity, in patients naïve to the anti-tumor necrosis factor alpha agents and after switching from IFX, and will be summarized in this review.

Biosimilar Monoclonal Antibodies for Inflammatory Bowel Disease: Current Comfort and Future Prospects.

Biosimilars are biologic medicines that enter the market after a patent for an original reference product expires. The European Medicines Agency (EMA) developed a stringent legislation process for biosimilar monoclonal antibodies, whereby similarity to the reference medicinal product in terms of quality characteristics, biological activity, clinical safety and efficacy must be demonstrated. Biosimilar infliximab CT-P13 was the first biosimilar monoclonal antibody to receive EMA marketing authorization, and further biosimilar molecules are being developed. The phase I and III clinical trials were conducted in ankylosing spondylitis and rheumatoid arthritis, and the use of CT-P13 in inflammatory bowel disease (IBD) was extrapolated on the results of these trials. Medical professionals were initially concerned about the reversed engineering process, the novel legal framework and the lack of clinical data in IBD. Emerging real-world data have confirmed the similarities between CT-P13 and the reference product in terms of efficacy, safety and immunogenicity in IBD. The cost reduction represented by biosimilars promotes industry competition and improves treatment access with sustained quality of care. This article reviews the existing and emerging clinical data for CT-P13 and a future perspective on biosimilar use in IBD.

New molecules in the treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a disorder of unknown aetiology that provokes chronic inflammation of the gastrointestinal tract. Anti-tumor necrosis factor drugs have represented a major advance in the treatment of IBD patients in the last few years and also have a good safety profile. Nevertheless, these treatments are not effective in all patients and, in initial responders, there can be a loss of response in the long-term. Consequently, new treatments are needed for IBD, aimed at distinct therapeutic targets. In the last few years, new molecules have been incorporated into the therapeutic armamentarium of IBD patients. Golimumab is an anti-tumor necrosis factor monoclonal antibody with demonstrated effectiveness in the treatment of ulcerative colitis. The use of CT-P13 (biosimilar infliximab) has been approved in Europe for the same indications as the original infliximab. More recently, vedolizumab, an anti-α4β7 integrin monoclonal antibody, has been approved for the treatment of Crohn's disease and ulcerative colitis. A large number of molecules are currently under development, some of which will, in the future, broaden the therapeutic options available in the treatment of IBD patients. Finally, in the next few years, studies should aim to identify factors predictive of response to the distinct biological agents for IBD in order to allow personalized selection of the best therapeutic alternative for each patient.

Nuevas moléculas en el tratamiento de la enfermedad inflamatoria intestinal

Inflammatory bowel disease (IBD) is a disorder of unknown aetiology that provokes chronic inflammation of the gastrointestinal tract. Anti-tumor necrosis factor drugs have represented a major advance in the treatment of IBD patients in the last few years and also have a good safety profile. Nevertheless, these treatments are not effective in all patients and, in initial responders, there can be a loss of response in the long-term. Consequently, new treatments are needed for IBD, aimed at distinct therapeutic targets.In the last few years, new molecules have been incorporated into the therapeutic armamentarium of IBD patients. Golimumab is an anti-tumor necrosis factor monoclonal antibody with demonstrated effectiveness in the treatment of ulcerative colitis. The use of CT-P13 (biosimilar infliximab) has been approved in Europe for the same indications as the original infliximab. More recently, vedolizumab, an anti-α4β7 integrin monoclonal antibody, has been approved for the treatment of Crohn's disease and ulcerative colitis. A large number of molecules are currently under development, some of which will, in the future, broaden the therapeutic options available in the treatment of IBD patients.Finally, in the next few years, studies should aim to identify factors predictive of response to the distinct biological agents for IBD in order to allow personalized selection of the best therapeutic alternative for each patient.

Clinical Experience of the Use of CT-P13, a Biosimilar to Infliximab in Patients with Inflammatory Bowel Disease: A Case Series.

CT-P13 is the first biosimilar monoclonal antibody to infliximab. However, the antibody was tested only in rheumatoid arthritis and ankylosing spondylitis, which demonstrated equivalence to the originator in efficacy, safety, and pharmacokinetic profile. Extrapolation of its efficacy and safety to other pathologies is tenuous. Interchangeability with its originator is another unclear area. We aimed to describe the experience of CT-P13 use in inflammatory bowel disease at a tertiary center. Seventeen subjects diagnosed with Crohn's disease (CD, n = 8) or ulcerative colitis (UC, n = 9) who were administered CT-P13 from November 2012 to October 2013 at Dongguk University Ilsan Hospital were retrospectively enrolled. Medical records analyzed included patients' characteristics, previous history of anti-tumor necrosis factor administration, response and remission to this biosimilar antibody, disease flare-up, and adverse drug reaction. Male-female ratio was 1.8. Mean age was 35.4 years (range 15-57). Mean number of CT-P13 administrations was 4.2 ± 1.9. Induction treatments were done in five UC and three CD patients. Clinical response and remission at 8 weeks were achieved in seven patients (five UC and two CD). One CD patient did not respond to CT-P13. Nine patients in maintenance with the originator were interchanged with CT-P13 (four UC and five CD patients). One UC patient experienced arthralgia and CT-P13 was discontinued. One patient experienced loss of response during the study period. CT-P13 may have biosimilarity and interchangeability with its originator in inflammatory bowel disease. A large, randomized, double-blind, prospective study is needed.