Switching from infliximab to biosimilar in inflammatory bowel disease: overview of the literature and perspective.
ABSTRACT: Background:Biological therapy has revolutionized the treatment of inflammatory bowel disease (IBD). After the expiration of patents for biological innovator products, development of biosimilars increased. CT-P13 was the first biosimilar approved for the same indications as the reference product; however, the approval was based on extrapolated data from rheumatoid arthritis and ankylosing spondylitis. Our aim was to review clinical studies about switching from originator infliximab (IFX-O) to biosimilar infliximab (IXF-B) in IBD, focusing on recently published data and the future of biosimilars. Methods:The PubMed database was searched for original articles published up to 1 December 2018 reporting data on IFX-B in IBD. Results:A total of 29 studies assessing switching from IFX-O to IFX-B, 14 assessing induction therapy with IFX-B were found. Efficacy, safety and immunogenicity were discussed. Studies confirm that CT-P13 is safe and equally efficient as the reference product for both induction and maintenance therapy; and that switching from the reference product to biosimilar is non-inferior to continuous biosimilar use. However, efficacy and safety data on Flixabi (SB2) in IBD patients is lacking. Conclusion:Switching from the originator to a biosimilar in patients with IBD is acceptable, although scientific and clinical evidence is lacking regarding reverse switching, multiple switching and cross-switching among biosimilars in IBD patients.
Project description:Many reference biological therapies have now reached or are near to patent expiry, and therefore a number of biosimilars have been or will be developed. The term biosimilar can be defined as a biotherapeutic product that is similar in efficacy, safety and quality to the licensed reference product. Biosimilars may lead to a reduced price and significant cost savings for the health community and hopefully more patients globally will have easier access to biological therapy when indicated. CT-P13, which is a TNF-alfa inhibitor, is the first monoclonal antibody biosimilar being used in clinical practice. The drug is approved for all indications as an innovator product although clinical efficacy has only been demonstrated in rheumatic diseases. Until now the number of patients with inflammatory bowel disease (IBD) treated with CT-P13 is confined, but experience is continuously growing. Based on current data, CT-P13 seems to be efficacious and generally well tolerated in IBD especially in patients who are naïve to biological therapy. Knowledge with regard to interchangeability between CT-P13 and the originator infliximab is however, still rather sparse and more data are desired. Immunogenicity and long-term safety related to CT-P13 are other areas of great importance and good and reliable postmarketing pharmacovigilance is therefore required in the coming years.
Project description: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.
Project description:INTRODUCTION:TNF-?-neutralizing antibodies, such as infliximab (IFX) and adalimumab (ADA), are effective in the treatment of inflammatory bowel diseases (IBD), but they are expensive and become ineffective when patients develop anti-IFX or anti-ADA antibodies (ATI and ATA, respectively). Second-generation anti-TNF-? antibodies, such as Golimumab, Etanercept, Certolizumab-pegol and IFX biosimilars, may solve these issues. AIM:To determine the neutralizing capacity of first- and second generation anti-TNF-? antibodies and to determine whether ATI show cross-reactivity with the IFX biosimilar CT-P13 (Inflectra). METHODS:TNF-? neutralization was measured using a quantitative TNF-? sensor assay consisting of HeLa 8D8 cells that express the Green Fluorescence Protein (GFP) under control of a NF-?B response element. All available anti-TNF-? drugs and the IFX biosimilar CT-P13 (Inflectra) were tested for their TNF-?-neutralizing capacity. In addition, patient sera with ATI were tested for their potential to block the activity of IFX, IFX (F)ab2-fragment, biosimilar CT-P13 (Inflectra) and ADA. RESULTS:TNF-? strongly induced GFP expression in Hela 8D8 cells. Higher concentrations of first-generation anti-TNF-? drugs were required to neutralize TNF-? compared to the second-generation anti-TNF-? drugs. Serum of IBD patients with proven ATI blocked TNF-?-neutralizing properties of IFX biosimilar CT-P13 (Inflectra), whereas such sera did not block the effect of ADA. CONCLUSION:The second-generation anti-TNF-? drugs show increased TNF-?-neutralizing potential compared to first-generation variants. ATI show cross-reactivity toward IFX biosimilar CT-P13 (Inflectra), consequently patients with ATI are unlikely to benefit from treatment with this IFX biosimilar.
Project description:BACKGROUND:In 2014 and 2015, biosimilars for the drugs filgrastim, infliximab, and insulin glargine were approved for use in Canada. The introduction of biosimilars in Canada could provide significant cost savings for the Canadian healthcare system over originator biologic drugs, however it is known that the use of biosimilars varies widely across the world. The aim of this study was to estimate the use of biosimilars in Canada and potential cost-savings from their use. METHODS:We performed a retrospective analysis of Canadian drug purchases for filgrastim, infliximab, and insulin glargine from July 2016 to June 2018. This was a cross-sectional study and the time horizon was limited to the study period. As a result, no discounting of effects over time was included. Canadian drugstore and hospital purchases data, obtained from IQVIA™, were used to estimate the costs per unit and unit volume for biosimilars and originator biologic drugs within each province. Potential cost-savings were calculated as a product of the units of reference originator product purchased and the cost difference between the originator biologic and its corresponding biosimilar. RESULTS:The purchase of biosimilars varied by each province in Canada, ranging from a low of 0.1% to a high of 81.6% of purchases. In total, $1,048,663,876 Canadian dollars in savings could have been realized with 100% use of biosimilars over the originator products during this 2?year time period. The potential savings are highest in the province of Ontario ($349 million); however, even in smaller markets (PEI and Newfoundland), $28 million could have potentially been saved. Infliximab accounted for the vast majority of the potential cost-savings, whereas the purchases of the biosimilar filgrastim outpaced that of the originator drug in some provinces. In sensitivity analyses assuming only 80% of originator units would be eligible for use as a biosimilar, $838 million dollars in cost savings over this two-year time period would still have been realized. CONCLUSIONS:The overall use of biosimilar drugs in Canada is low. Policy makers, healthcare providers, and patients need to be informed of potential savings by increased use of biosimilars, particularly in an increasingly costly healthcare system.
Project description:PURPOSE OF REVIEW:Biosimilars of the reference biologic therapeutics infliximab, etanercept, adalimumab, and rituximab are entering the market. Clinical and real-world data on the effects of reference ? biosimilar switching are limited. This review was carried out to assess the current body of switching data. RECENT FINDINGS:Fifty-three switching studies were identified. Infliximab publications covered CT-P13 (25 studies), SB2 (1), infliximab NK (1), and unspecified infliximab biosimilars (2). Etanercept publications covered SB4 (2) and GP2015 (2). Adalimumab publications covered ABP 501 (2) and SB5 (1). Rituximab publications covered CT-P10 (1). Efficacy and safety data generally showed no differences between patients who switched treatments versus those who did not. No differences were seen pre- and post-switch. Immunogenicity data were presented in 19/37 (51%) studies. Additional data from switching studies of these therapies are still required, as is continuing pharma-covigilance. Switching should remain a case-by-case clinical decision made by the physician and patient on an individual basis supported by scientific evidence.
Project description:<h4>Background</h4>Biosimilar versions of widely prescribed drugs, including the tumour-necrosis factor antagonist infliximab, are becoming increasingly available. As biosimilars are not identical copies of reference products, evidence may be required to demonstrate that switching between a reference biologic and biosimilars is safe and efficacious. To establish interchangeability, US Food and Drug Administration guidance states that studies must demonstrate that biosimilars remain equivalent or non-inferior to a reference product after multiple switches between products.<h4>Aims</h4>To investigate the evidence evaluating the safety and efficacy of switching between reference and biosimilar infliximab in patients with inflammatory disorders, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.<h4>Methods</h4>Published studies presenting data on switching between reference and biosimilar infliximab were identified by searching the MEDLINE database. Congress abstracts were identified by searching the EMBASE database and manually searching abstracts from relevant congresses.<h4>Results</h4>A total of 113 journal articles and 149 abstracts were found. Of these, 70 were considered relevant and included in this analysis. Most of the publications were uncontrolled, observational studies. Data from six randomised, controlled trials were identified. In general, the evidence revealed no clinically important efficacy or safety signals associated with switching.<h4>Conclusions</h4>While available data have not identified significant risks associated with a single switch between reference and biosimilar infliximab, the studies available currently report on only single switches and were mostly observational studies lacking control arms. Additional data are needed to explore potential switching risks in various populations and scenarios.
Project description:Background:As the patents of originator biologics are expiring, biosimilar versions are becoming available for the treatment of inflammatory bowel disease (IBD). However, published switch studies of the first infliximab biosimilar, CT-P13, have delivered ambiguous results that could be interpreted as showing a trend towards inferior effectiveness in Crohn's disease (CD) compared with ulcerative colitis (UC). The aim of this study was to investigate the effectiveness and safety of switching IBD patients from treatment with Remicade to CT-P13. Methods:In this prospective observational cohort study, all adult IBD patients on Remicade treatment, at four hospitals, were switched to CT-P13. The primary endpoint was change in clinical disease activity at 2, 6, and 12 months after the switch. Secondary endpoints were subgroup analyses of patients with and without concomitant immunomodulators; changes in biomarkers, quality of life, drug trough levels and anti-drug antibodies (ADAbs); and adverse events. Results:A total of 313 IBD patients were switched (195 CD; 118 UC). There were no significant changes in clinical disease activity, quality of life, biomarkers (except a small but significant increase in albumin in CD) including F-calprotectin, drug trough levels, or proportion of patients in remission. Disease worsening rates were 14.0% for CD and 13.8% for UC; and 2.7% developed ADAbs and 2.2% developed serious adverse events. Conclusions:This is the largest study of switched IBD patients published to date, and it demonstrates that switching from Remicade to CT-P13 may be done with preserved therapeutic effectiveness and safety in both CD and UC.
Project description:BACKGROUND AND OBJECTIVES:The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures. METHODS:Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. RESULTS:Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. CONCLUSION:The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.
Project description:The goal of this narrative review was to summarize immunogenicity data of biosimilars or biosimilar candidates for rheumatic diseases, plaque psoriasis, or inflammatory bowel disease (IBD), available in peer-reviewed publications or regulatory documents. PubMed records and regulatory documents were searched for immunogenicity data of TNF? or CD20 inhibitor biosimilars or biosimilar candidates. Data collected included the proportion of patients positive for anti-drug antibodies (ADAbs), proportion with neutralizing antibodies (nAbs) among ADAb-positive patients, ADAb/nAb assay characteristics, cross-reactivity, and the effects of ADAbs on pharmacokinetics, pharmacodynamics, efficacy, and safety. We identified eight biosimilars or biosimilar candidates for adalimumab (BI 695501, SB5, ABP 501, GP2017, PF-06410293, MSB-11022, FKB-327, ZRC-3197) four for etanercept (SB4, GP2015, CHS-0214, LBEC0101), and three each for infliximab (SB2, CT-P13, GP1111) and rituximab (CT-P10, GP2013, PF-05280586) with immunogenicity data. Randomized, head-to-head trials with reference products varied in design and methodology of ADAb/nAb detection. The lowest proportions of ADAb-positive (0-13%) and nAb-positive patients (0-3%) were observed in the trials of etanercept and its biosimilars, and the highest with adalimumab, infliximab, and their biosimilars (ADAbs: ??64%; nAbs: ??100%). The most common method of ADAb detection was electrochemiluminescence, and ADAb positivity was associated with nominally inferior efficacy and safety. Overall, there were no significant immunogenicity differences between biosimilars and reference products. However, there are many discrepancies in assessing and reporting clinical immunogenicity. In conclusion, immunogenicity data of biosimilars or biosimilar candidates for TNF? or CD20 inhibitors were collected in trials that varied in design and procedures for ADAb/nAb detection. In general, immunogenicity parameters of biosimilars are similar to those of their reference products.
Project description:Objective:The introduction of biosimilars for rheumatologic diseases (RDs) has provided a potentially lower-cost therapy compared with their bio-originator products; however, adoption of biosimilars may be challenged by patient perceptions. The objective of this study was to describe patients' perspectives of switching from infliximab to infliximab-dyyb. Methods:This was a survey of adult patients with RDs who qualified for switching from infliximab to infliximab-dyyb therapy between September 1 2017 and January 31 2018. Verbal consent was obtained prior to administration of a telephone survey. Survey questions were focused on the safety, efficacy, and knowledge of biosimilar therapy. Results:A total of 108 patients were identified with 52 (48%) patients consenting to study participation. Forty (77%) and 12 (23%) patients reported switching and not switching, respectively, to infliximab-dyyb. Regarding disease control, most respondents (80%) were satisfied to very satisfied with the switch to infliximab-dyyb. Major concerns reported for switching included not knowing enough about the medication (38%), potential side effects (35%), and loss of disease activity control (35%). Conclusion:Overall, patients reported satisfaction with switching from infliximab to infliximab-dyyb, but concerns regarding safety and efficacy were expressed. Patient involvement in the switching decision-making process may allay concerns and enhance biosimilar uptake.