Biosimilar Infliximab Research Articles

P536 Comparison of outcomes of infliximab biosimilar CT-P13 with infliximab originator in patients with inflammatory bowel disease

Abstract Background Studies on the efficacy and safety of Infliximab (IFX) biosimilar CT-P13 and IFX originator are needed in Crohn’s disease (CD) and ulcerative colitis (UC). Methods The aim of this study was to evaluate the short and long-term clinical efficacy and safety of IFX biosimilar CT-P13 compared to IFX originator in adult patients with inflammatory bowel disease (IBD). Data were retrospectively collected. Therapeutic failure was defined as discontinuation of biological therapy because of primary lack of response (p-LOR), secondary loss of response (s-LOR, including steroid needed, IBD-related hospitalization, IBD-related surgery, and switch to other biotherapy) and serious adverse events (SAE). Results 252 patients who received IFX were identified between January 2007 and November 2021 (66 IFX biosimilar CT-P13 and 186 IFX originator). Data were analyzed for 188 CD (62.2% males; 34.6% biologics experienced; 27.7% IFX biosimilar CT-P13 / 72.3% IFX originator and 64 UC (59.4% males; 20.3% biologics experienced; 21.9% IFX biosimilar CT-P13 / 78.1% IFX originator). There were no significant differences between the two groups with respect to all demographic features at the beginning of the treatment (p>0.05). Median follow-up time was 1.58 years and 1.74 years after starting IFX in biosimilar CT-P13 and originator, respectively. There were no significant differences in the rates of p-LOR (4.5% vs. 5.4%, p>0.999) and SAE (6.1% vs. 15.6%, p=0.078) between IFX biosimilar CT-P13 and IFX originator, while the rate of s-LOR was significantly higher in IFX originator group (13.6% vs. %31.2, p=0.009). Considering all types of s-LOR, we did not detect significant differences between IFX biosimilar CT-P13 and IFX originator in the rates of IBD-related hospitalization (10.6% vs. 15.6%, p=0.430) and IBD-related surgery (7.6% vs. 12.4%, p=0.403). Nevertheless, the rates of steroid needed (0.0% vs. 6.5%, p=0.040), and switch to another biotherapy (4.5% vs. 19.4%, p=0.008) were significantly higher in IFX originator. There were also no significant differences in terms of these outcomes between concomitant immunomodulator therapy and monotherapy within IFX biosimilar CT-P13 and IFX originator (p>0.05). Conclusion In this study, outcomes did not reveal significant differences between IFX biosimilar CT-P13 and IFX originator in terms of the p-LOR and SAE. There was no difference between the two groups in the IBD-related hospitalization and IBD-related surgery, however the rates of steroid needed and switch to another biotherapy were significantly higher in the IFX originator within the s-LORs group. No difference was observed in terms of all outcomes between the two groups treated with monotherapy or concomitant immunomodulator therapy.

P599 Azathioprine in the prevention of anti-infliximab antibody formation: A pilot dose-finding study

Abstract Background The infliximab (IFX) therapy is associated with production of the anti-IFX antibodies (ATI), that can lead to infusion reactions and affect the therapeutic response. Concomitant use of azathioprine (AZA) in patients treated with IFX is recommended. A lower dosage is suggested however without further specification. The aim of this study is to determine the threshold dose of AZA to prevent ATI formation during IFX therapy. Methods The Retrospective, multicenter (Zlin, Prague, Czech rep.), observational study. The adult patients with ulcerative colitis or Crohn’s disease, treated with IFX in scheduled regimen (5mg/kg á 8 weeks), on concomitant azathioprine therapy (> 3 month), without any other immunomodulator or steroids, who were tested for IFX and ATI levels, were enrolled. The primary outcome measure was the dose of AZA and ATI positivity (cut-off > 3 AU/ml), secondary measure included interval to the appearance of ATI. ROC analysis was used to evaluate AZA dose and interval predictive of the ATI positivity. Results Of the 62 patients analyzed (53% female, mean age 34.1 years), 76% had Crohn’s disease. 29 (47%) subjects were treated with biosimilar IFX. The mean dose of AZA was 1.5 ± 0.5 mg/kg, and the duration of IFX treatment was 44.2 ± 41.4 months. ATI ′s were present in 23 subjects (37.1%), with no difference between original and biosimilar IFX. ATI positivity was associated with lower mean IFX levels (1.8 ± 2.4 vs 6.0 ± 5.1ug/ml, p=0.002). The threshold dose of AZA for ATI positivity was predicted to 1.2 mg/kg (95% CI 0.6–1.8, p=0.02, AUC 0.682) and the time to antibody appearance to 13.0 months (95% CI 5.0–49.1, p=0.02, AUC 0.672). Conclusion The dose of AZA lower than 1.2 mg/kg was associated with a higher chance of anti-IFX antibodies development. Their appearance may be expected after 1 year from the initiation of the combo IFX therapy. ATI′s are associated with reduced IFX through levels.

P483 Patient-reported quality of life, anxiety, and depression associated with switching originator infliximab to biosimilar

Abstract Background Non-medical switching from biologics to biosimilars is becoming increasingly common. Previous studies have demonstrated efficacy and safety of switching originator to biosimilar infliximab in inflammatory bowel disease (IBD) patients. Limited data exist on patient-reported quality of life (QOL) and possible emotional duress associated with these switches. The purpose of this study was to describe the impact of non-medical switches to infliximab biosimilars on QOL, anxiety, and depression. Methods This was a retrospective review of all IBD patients switched from originator to infliximab biosimilar at a large multicenter gastroenterology private practise in Texas. Patients were asked to complete standardised questionnaires on a quarterly basis beginning 3/2021, concurrent with large US payor policy changes mandating non-medical biosimilar switches. The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) was used to assess disease-specific QOL. The Hospital Anxiety and Depression Scale (HADS) was used to determine anxiety and depression. All questionnaires through 10/2021 were collected and designated as “pre” or “post” based on the date of the patient’s non-medical switch to infliximab biosimilar. Wilcoxon rank sum test was used to compare scores. We also performed subset analyses on patients with both “pre” and “post” questionnaires with paired t-test. Results From 3/2021 to 10/2021, a total of 81 questionnaires were submitted by 54 patients who underwent non-medical switches to an infliximab biosimilar. 30 questionnaires were submitted prior to (“pre”) and 51 questionnaires were submitted after (“post”) the non-medical switch. Median “pre” SIBDQ score was 58 (IQR 53–63). Median “pre” HADS-Anxiety and HADS-Depression score were 3.5 (IQR 1–6) and 1 (IQR 0–5), respectively. As shown in Figure 1, “post” scores were unchanged [SIBDQ 59 (IQR 54–63); HADS-Anxiety 3 (IQR 1–7); HADS-Depression 2 (IQR 1–4)]. Subset analyses included 14 patients who submitted both “pre” and “post” questionnaires. Similarly, no significant changes were observed [Figure 2]. Conclusion Non-medical switches to infliximab biosimilar did not affect QOL or mental health. To our knowledge, this is the first biosimilar switch study to incorporate anxiety and depression measures. These relationships should continue to be assessed.

The effectiveness and safety of switching therapy with an original drug to biosimilars in treatment of inflammatory bowel diseases

Introduction. Inflammatory bowel diseases are a group of chronic, immune-mediated diseases of unknown etiology. Etiotropic therapy of IBD does not exist, all drugs used to treat IBD have a pathogenetic effect. In the treatment of IBD biologic therapy is used. The most previously registered group of biologics are anti-TNF-α. But, after the expiration of the relevant patents, biosimilars appeared on the market (analogs, comparable in quality to the already approved reference product).Materials and methods. A retrospective study was conducted on the basis of the Ryzhikh Natianal Medical Research Centre for Coloproctology of the Ministry of Health of the Russia, which included 46 patients who switched from therapy with the original infliximab or adalimumab to biosimilar therapy.Discussion. This study showed that when switching therapy with the original drugs infliximab and adalimumab to biosimilars, the effectiveness of therapy does not significantly decrease with the use of biosimilars Infliximab BIOCAD and Dalibra. However, a statistically significant decrease in efficacy was revealed when switching from therapy with the original Infliximab to Flammegis. Considering that the use of biosimilars can reduce the cost of treatment and reduce the burden on the health budget, it is necessary to continue this study in order to obtain longer-term results.

IN VITRO CELL-BASED ASSAYS FOR SCREENING AND COMPARISON OF TNF-Α AND IL-17A INHIBITORS AND THEIR BIOSIMILARS

Cell-based bioassays have been developed to assess the biological activity of TNF-α and IL-17A inhibitors based on primary human cell cultures obtained from tissues of juvenile donors. The Fibro-bioassay is based on the analysis of IL-17A dose-dependent production of inflammatory cytokines synthesized by human foreskin fibroblasts (HFF). Using this bioassay, it has been shown that Netakimab (Biocad, RF) is a highly effective inhibitor of IL-17A. Using the Chondro test system the biological activity of TNF-α inhibitors was compared: the original molecule Remicade (MSD, Ireland) with its biosimilar Infliximab (Biocad, Russia).

POSA6 Use of Real-World Evidence to Evaluate Infliximab Biosimilars: A Scoping Review

Infliximab biosimilars (IFX-B) have been introduced in recent years as therapeutic alternatives to originator infliximab (IFX-O). These have been approved in Europe, the United States, and Canada for the treatment of chronic conditions such as rheumatoid arthritis and Crohn’s disease. Real-world evidence (RWE) may provide valuable information about the long-term effectiveness and safety of IFX-B compared to IFX-O outside of the clinical trial setting, and scoping reviews may guide research question development for future work in this area.

Mandatory nonmedical switching from originator to biosimilar infliximab in patients with inflammatory arthritis and psoriasis in British Columbia: a cohort study.

Background:In 2019, British Columbia’s public drug plan, PharmaCare, was the first in Canada to implement a nonmedical switching policy from originator infliximab to its biosimilar, for patients with inflammatory arthritis or psoriasis. We aimed to detect signals of impact on health services utilization during the first year of policy implementation and to provide early data to policy-makers.Methods:We constructed cohorts of users of originator infliximab: 3 historical cohorts (2016–2018) and 1 policy cohort (2019). We extracted data from BC Ministry of Health databases from 2015 to 2020, as we followed each cohort for 365 days from May 27 of each cohort’s respective year. We excluded patients with gastrointestinal conditions and those not covered by PharmaCare. We examined the cumulative incidence of infliximab prescription refills, switching to other biologic drugs and use of additional health services. A log-likelihood ratio of 1.96 compared with the null hypothesis was used as the threshold for differences between the policy cohort and the historical cohorts.ResultsThe study included a total of 572 unique patients: 520 in the 2016 historical cohort, 461 in the 2017 historical cohort, 423 in the 2018 historical cohort and 377 in the policy cohort (with some patients included in multiple cohorts; 335 [58.6%] were included in all 4 cohorts). During months 8 and 9 of follow-up, a transient signal was observed in infliximab refills (7.2% decrease in refilling infliximab for the fourth time for the policy cohort, log-likelihood ratio > 1.96). An anticipated increase in visits to specialists was observed from month 4 forward (15.0%, log-likelihood ratio > 1.96). No signal was observed for increased use of other health services (log-likelihood ratio < 1.96).Interpretation:Early monitoring did not detect signals of negative impacts on health services use during the first year of the policy. Detailed, longer-term cohort studies and hypothesis-testing methods could provide additional assurance about the safety of the policy.

Real-World Treatment Patterns and Physician Preferences for Biologics in Moderate-to-Severe Inflammatory Bowel Disease: Retrospective Chart Review in Europe.

With many options available for treating inflammatory bowel disease (IBD) in Europe, this study sought to characterize physician treatment preferences and real-world treatment patterns in patients with moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). This was a retrospective, noninterventional, physician-administered study. Gastroenterologists and general practitioners (n = 348) in France, Germany, and the United Kingdom provided information on treatment preferences and extracted information from records of patients with moderate-to-severe UC (n = 587) or CD (n = 417) who had received biologic, biosimilar or Janus kinase inhibitor therapies (2014-2019) and had IBD-related medical history available 6 months before and after treatment initiation. Physicians largely preferred infliximab and adalimumab or their biosimilars as first-line therapy for UC (originators, 65.8%; biosimilars, 26.1%) and CD (originators, 61.8%; biosimilars, 30.5%). Effectiveness was the most cited reason for treatment preference (92%-93% of physicians). Three-quarters of patients (UC, 75.8%; CD, 73.6%) received infliximab or adalimumab originators in the first line, with more patients receiving infliximab biosimilars than adalimumab biosimilars (12.4%-12.5% and 0.5%-4.1%, respectively, across UC and CD). Persistence was longer for first-line infliximab than adalimumab (UC, 26.6 vs 21.2 months; CD, 31.2 vs 26.7 months) and was generally shorter for their respective biosimilars. Nonbiologic treatments were used in combination with biologics in 14.1% (UC) and 11.5% (CD) of patients. Most patients received 1 biologic therapy (UC, 90.6%; CD, 83.2%); only 9.4% (UC) and 16.8% (CD) received a second biologic. Infliximab and adalimumab originators dominated first-line biologic therapy for moderate-to-severe UC and CD. Understanding real-world treatment patterns can help assess new treatment uptake and suggest opportunities for improving treatment.

Biosimilární monoklonální protilátky v terapii idiopatických střevních zánětů Důležitý milník ve vývoji terapie Crohnovy nemoci a ulcerózní kolitidy, nebo jen sofistikovaná generika?

Summary: In 2013, EMA approved the fi rst biosimilar infl iximab CT-P13 for clinical practice in all indications of the original infl iximab. Since 2015, biosimilar infl iximab has been extensively used in patients with Crohn‘s disease and ulcerative colitis also in the Czech Republic. Biosimilar infl iximab is very similar to the original infl iximab in terms of its macromolecular structure, and its clinical eff ects, adverse events and immunogenicity are identical to those of the original infl iximab. Biosimilar biologics which have been introduced in clinical practice signifi cantly reduced therapeutic costs and improved access to an innovative therapy and facilitated a new therapeutic strategy, with pro-active drug monitoring and fl exibility in dosing. Biosimilars are associated with a signifi cant improvement in the therapeutic armamentarium, which makes them one of the important therapeutic milestones in the treatment of infl ammatory bowel disease. Key words: bio similars – bio logic therapy – Crohn’s disease – ulcerative colitis

Comparison of performances of infliximab biosimilars CT-P13 versus SB2 in the treatment of inflammatory bowel diseases: a real-life multicenter, observational study in Italy

ABSTRACT Background To compare the performances of Infliximab (IFX) biosimilar CT-P13 and SB2 in the treatment of Inflammatory Bowel Diseases (IBD) outpatients in Italy. Research Design and Methods Three hundred and eighty IBD outpatients were retrospectively evaluated. The primary endpoint was to compare the two IFX biosimilars in terms of reaching and maintenance of remission at any timepoint. Results 197 patients with Ulcerative Colitis (UC) and 183 patients with Crohn’s Disease (CD) treated with CT-P13 or SB2 and having a median (IQR) follow-up of 12 (6–36) months were compared: 230 (60.5%) were naïve to anti-TNFα, 20 (5.26%) were switched from IFX originator or from IFX CT-P13 to IFX SB2. Clinical remission was achieved in 133 (67.5%) UC patients and in 164 (89.6%) CD patients (p < 0.000), with no differences between CT-P13 and SB2 in the rate of remission in UC (p = 0.667) and CD (p = 0.286). Clinical response, steroid-free remission, rate of surgery, mucosal healing (MH) in UC, switching from IFX originator or from other biosimilar, and safety were similar. Higher MH rate was obtained in CD patients treated with CT-P13 (p = 0.004). Conclusion This first comparative study found that both IFX biosimilars CT-P13 and SB2 are effective and safe in managing IBD outpatients.

Comparison of treatment retention of originator vs biosimilar products in clinical rheumatology practice in Sweden.

ObjectivesTo compare treatment retention between biosimilars and their originator products among first starters (etanercept, infliximab, adalimumab and rituximab), as well as after non-medical switch.MethodsPatients with rheumatic diseases starting, for the first time, an originator or biosimilar etanercept, infliximab, adalimumab or rituximab were identified in the national Swedish Rheumatology Quality Register. Moreover, patients switching from an originator to its biosimilar were identified and individually matched to patients continuing on the originator. One-year treatment retention was calculated and hazard ratios (HR) for discontinuation with 95% CIs were estimated, adjusting for comorbidities and socio-economic factors.ResultsIn total, 21 443 first treatment courses were identified. The proportion of patients still on the drug at 1 year and the HR for discontinuation revealed no differences across adalimumab (Humira, Imraldi, Amgevita and Hyrimoz) nor across rituximab products (Mabthera, Ritemvia/Truxima and Rixathon). The proportions on the drug at 1 year were similar for Benepali (77%) and Enbrel (75%) and the adjusted HR for Benepali compared with Enbrel was 0.91 (95% CI 0.83, 0.99). For infliximab, the proportion still on the drug at 1 year was 67% for Remicade and 66% for Remsima/Inflectra and the HR compared with Remicade was 1.16 (95% CI 1.02, 1.33). Among 2925 patients switching from an originator drug to one of its biosimilars, we noted no statistically significant or clinically relevant differences in drug survival compared with those who remained on originator therapy.ConclusionThis large observational study supports the equivalence of biologic DMARD biosimilar products and originators when used in routine rheumatology care.

Penetration rate of anti-TNF biosimilars and savings at 5 years after their introduction in French hospitals

Since the expiry of the patents on originator anti-TNF agents in Europe, France has authorized the sale of biosimilars. The penetration rate of anti-TNF agents and their biosimilars, and the cost savings driven by the introduction of biosimilars appears to vary widely. This study aimed to describe the market share of anti-TNFs and their biosimilars, and the cost savings generated by the introduction of biosimilars in French hospitals 5 years ago. The pharmaceutical component of the French national uniform hospital discharge data set database (PMSI) was used to study sales of infliximab, etanercept and adalimumab originators and biosimilars, and to estimate cost savings generated by the introduction of biosimilars onto the market, using the historical tariffs of the originators. The penetration rate of anti-TNF biosimilars in France in 76% for infliximab, 74% for etanercept and 77% for adalimumab. In 2020, Inflectra® (41%) was the Remicade® biosimilar with the highest sales volume, while Erelzi® (57%) and Amgevita® (64%) were the most widely sold biosimilars of Enbrel® and Humira® respectively. In terms of cost savings since the launch of biosimilars, overall, for all biosimilars taken together, over the 5-year period, a total of 824 million Euro was saved, in relation to the historical tariffs of the originators. This study shows firstly that the penetration rate of anti-TNF biosimilars in France 5 years after their launch is close to 80%. Secondly, we show that the cost savings generated by the use of biosimilars to anti-TNF agents exceed 820 million Euro over 5 years.

PP180 Optimal Treatment Sequence For Targeted Immune Modulators For The Treatment Of Moderate To Severe Ulcerative Colitis

IntroductionSeveral targeted immune modulators (TIMs) have demonstrated effectiveness in moderate-to-severe ulcerative colitis, including adalimumab, golimumab, infliximab, infliximab biosimilars, tofacitinib, ustekinumab, and vedolizumab. In addition to assessing individual TIMs, evaluating TIM sequences can inform clinical care as well as coverage and reimbursement policies. Our objective was to identify optimal treatment sequences based on maximum net health benefit (NHB), lowest total cost (cost minimizing), quality-adjusted life-year (QALY) maximization, or convenience (avoidance of intravenous treatments), and to evaluate their cost effectiveness compared with conventional treatment from the health sector perspective.MethodsWe developed a Markov model with eight-week cycles and a lifetime time horizon. The health states were active, clinical response without remission, remission, and death. TIM efficacy was informed by a network meta-analysis conducted by the Institute for Clinical and Economic Review. Sequences were generated by ranking TIMs and then conventional treatment according to NHB, cost minimization, QALY maximization, or convenience and combining top ranked TIMs in the biologic naïve and biologic experienced populations. NHB was calculated at USD 150,000 per QALY. Probabilistic sensitivity analysis (PSA) was undertaken to estimate the probability of each sequence having the highest NHB rank, QALY maximizing rank, and cost-minimizing rank.ResultsTwenty-one sequences were evaluated. The sequence with the highest NHB was infliximab followed by tofacitinib (-0.12 QALYs), which also had the lowest incremental costs (USD37,266). For orally and subcutaneously administered TIMs, the sequence of golimumab-tofacitinib had the highest NHB (-0.34 QALYs). Ustekinumab-vedolizumab was not only the top ranked sequence as measured by QALY maximization (0.172 incremental QALYs), but it also had the highest total incremental cost (USD166,094). Results of the PSA were consistent with deterministic rankings for the top-ranking sequences and showed that the top two or three regimens were close in magnitude.ConclusionsThe optimal sequence with regard to NHB and cost minimization was infliximab or biosimilars, followed by tofacitinib, adalimumab, or vedolizumab. Sequences that generated the most QALYs began with ustekinumab, followed by vedolizumab, tofacitinib, and adalimumab.

P013 Resolution of Infliximab Associated Infusion Hypersensitivity After Switching to Biosimilar Infliximab-dyyb.

Background: Administration of infliximab for the treatment of inflammatory bowel disease has a well-recognized risk of infusion-related (IR) adverse events. The recent introduction of the biosimilar infliximab-dyyb (Inflectra®) has been shown to have similar efficacy with comparable safety profile when compared to infliximab; however, although the active ingredients are similar, the inactive ingredients are different. We present a case of a 26-year-old female with ulcerative colitis who had resolution of her IR hypersensitivity when switched from infliximab to infliximab-dyyb. A 26-year-old female with a past medical history of ulcerative pancolitis presented to our clinic with the chief complaint of rash associated with her infliximab infusions. She described pruritic raised lesions which would occur on her upper and lower extremities during her infusions. She denied any shortness of breath or wheezing, and her symptoms were well controlled with methylprednisolone 40mg IV prior to her infusions. Previously, she had been treated for her UC with oral mesalamine, azathioprine and intermittent prednisone and did not have any adverse reactions to these medications. She has no known allergies to other medications and her peripheral eosinophil count was 1.6%. She was initially started on infliximab 5mg/kg every 8 weeks since 2013 and had achieved clinical as well as endoscopic remission with her most recent colonoscopy graded as Mayo 0. On account of her infusion reaction, drug antibodies were checked but were not detected. Infliximab level was 8.8 μg/ml. Due to insurance she was required to switch to infliximab-dyyb. After switching to the biosimilar, she has not had any infusion related reactions and no longer requires premedication with methylprednisolone with her infusions. Immediate IR reactions have been reported in 5-23% of IBD patients receiving infliximab and those who develop antibodies towards infliximab have a 2-fold risk of acute IR events. Side effects have been reported to be the primary reason for discontinuation of infliximab, and studies have shown that discontinuation can lead to an increased risk of relapse of inflammatory bowel disease. Although infliximab and infliximab-dyyb have analogous active ingredients, the inactive ingredients differ. Specifically, infliximab-dyyb lacks monobasic sodium phosphate and dibasic sodium phosphate, which acts as an emulsifier which we believe contributed to her IR with originator biologic infliximab. It is important to recognize these differences as IR hypersensitivities may be attributed to inactive ingredients; especially when antibodies are negative. Our case report suggests that a switch to biosimilar infliximab in patients may provide added benefit especially in those that have reactions occurring from inactive ingredients in the originator biologic.

Levels of Biosimilar Infliximab during and after Induction Treatment in Crohn's Disease and Ulcerative Colitis-A Prospective Polish Population Study.

Background: Primary lack or secondary loss of response to therapy with infliximab is a significant problem. This study aimed to evaluate the response to treatment in patients with Crohn’s disease (CD) and ulcerative colitis (UC) achieving therapeutic and sub-therapeutic trough levels of biosimilar infliximab (CT-P13). Results: A total of 65 patients (32 with CD and 33 with UC) were recruited. The overall response rate in both CD and UC patients exceeded 80%. There were no significant differences in treatment response and CT-P13 levels for patients with CD or UC. We did not find significant differences in the percentage of patients achieving drug levels of 3 μg/mL at week 6, 10, or 12; a significant decrease was observed at week 14. Up to 55.5% of patients with CD and 64.3% of patients with UC with sub-therapeutic CT-P13 levels at week 14 primarily responded to treatment. Conclusions: Intermediate measurements of drug levels at weeks 10 and 12 did not capture any pronounced decrease in infliximab concentrations below therapeutic levels in either group, thus suggesting no clinical usefulness. A significant percentage of patients primarily responded to treatment despite sub-therapeutic drug levels after the induction phase.

A Review of the Totality of Evidence for the Development and Approval of ABP710 (AVSOLA), an Infliximab Biosimilar.

ABP 710 (AVSOLA®) is a biosimilar to infliximab reference product (RP), a monoclonal antibody targeting tumor necrosis factor alpha (TNFα). It is approved in the USA and Canada for all the same indications as infliximab RP. Approval of ABP 710 was based on the totality of evidence (TOE) generated using a stepwise approach to assess its similarity with infliximab RP with regard to analytical (structural and functional) characteristics, pharmacokinetic parameters, and clinical efficacy and safety. ABP 710 was shown to be analytically similar to infliximab RP including in amino acid sequence, primary peptide structure, and glycan mapping and purity. ABP 710 was also demonstrated to be similar to infliximab RP with regard to functional characterization including in vitro binding, effector functions, and signaling pathways important for the mechanisms of action for clinical efficacy in multiple indications of immune-mediated inflammatory disorders including inflammatory bowel disease (IBD), especially binding to both soluble and membrane-bound TNFα. Pharmacokinetic similarity of ABP 710 with infliximab RP was demonstrated in healthy volunteers following a single 5 mg/kg intravenous dose. Comparative clinical efficacy of ABP 710 with infliximab RP was demonstrated in patients with rheumatoid arthritis. Safety and immunogenicity were also demonstrated to be similar for both ABP 710 and the RP. Overall, the TOE supported the conclusion that ABP 710 is highly similar to infliximab RP and supported scientific justification for extrapolation to all approved indications of infliximab RP, including IBD.

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.

Infliximab use in the Netherlands: Uptake and characteristics of originator and biosimilars over time.

The objective of this retrospective cohort study was to provide an overview of the utilization of originator and biosimilar infliximab in the Netherlands. All infliximab dispensings were selected from the PHARMO In-patient Pharmacy Database from 2002-2018. Descriptive analyses were performed in order to characterise initiators and to describe switching patterns over time. Overall, 3840 patients with 61 274 infliximab dispensings were identified. 2496 patients initiated an originator infliximab and 777 patients initiated a biosimilar infliximab. Overall, 57% of the patients was female and mean age was 43.2 years. Both originators and biosimilars were mostly prescribed by gastroenterologists, followed by internists and rheumatologists. After market authorisation of the first biosimilar, the proportion of new patients initiating the biosimilar increased from 39% in 2015 to 91% in 2018. Out of 704 patients eligible for switching 34% switched. Among switchers, the proportion of females was 60% and mean age at index was 45.1 years. Among nonswitchers, 55% were female and mean age was 39.8 years. The median time to switch was 1.7 years and switchers were most frequently initiated on infliximab by a rheumatologist (42%), while nonswitchers were most frequently initiated by a gastroenterologist (42%). The results of this large population-based cohort show an increase in biosimilar initiation in daily clinical practice. The number of switchers remains relatively low as nonmedical switch is not encouraged in the Netherlands.

Large-Scale Postmarketing Surveillance of Biological Drugs for Immune-Mediated Inflammatory Diseases Through an Italian Distributed Multi-Database Healthcare Network: The VALORE Project.

BackgroundBiological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings.ObjectiveThe aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID.MethodsA retrospective cohort study was conducted using 13 Italian regional claims databases during 2010–2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association.ResultsFrom a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015–2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively.ConclusionThe VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010–2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40259-021-00498-3.