Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials (LIBERTY).

BACKGROUND & AIMS: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. The LIBERTY studies aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. (Co-) primary end points were clinical remission and endoscopic response (CD) and clinical remission (UC) at week 54 (all-randomized population). RESULTS: Overall, 396 patients with CD and 548 patients with UC received induction treatment. At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC-treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001). In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001). Achievement of key secondary end points was significantly higher with CT-P13 SC vs placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified. CONCLUSIONS: CT-P13 SC was more effective than placebo as maintenance therapy and was well tolerated in patients with moderately to severely active CD or UC who responded to CT-P13 IV induction. CLINICALTRIALS: gov, Numbers: NCT03945019 (CD) and NCT04205643 (UC).

Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease.

BACKGROUND & AIMS: This study compared pharmacokinetics, symptomatic and endoscopic efficacy, safety, and immunogenicity of a subcutaneous formulation of the infliximab biosimilar CT-P13 (CT-P13 SC) vs intravenous CT-P13 (CT-P13 IV) in patients with inflammatory bowel disease (IBD). METHODS: This randomized, multicenter, open-label, parallel-group, phase 1 study enrolled tumor necrosis factor inhibitor-naïve patients with active ulcerative colitis (total Mayo score 6-12 points with endoscopic subscore ≥2) or Crohn's disease (Crohn's Disease Activity Index 220-450 points) at 50 centers. After CT-P13 IV induction at Week (W) 0/W2, patients were randomized (1:1) to receive CT-P13 SC every 2 weeks (q2w) from W6 to W54 or CT-P13 IV every 8 weeks from W6 to W22. At W30, all patients receiving CT-P13 IV switched to CT-P13 SC q2w until W54. The primary endpoint was noninferiority of CT-P13 SC to CT-P13 IV for observed predose CT-P13 concentration at W22 (Ctrough,W22), concluded if the lower bound of the 2-sided 90% confidence interval (CI) for the ratio of geometric least-squares means exceeded 80%. RESULTS: Overall, 66 and 65 patients were randomized to CT-P13 SC and CT-P13 IV, respectively. The primary endpoint of noninferiority was met with a geometric least-squares means ratio for Ctrough,W22 of 1154.17% (90% CI 786.37-1694.00; n = 59 [CT-P13 SC]; n = 57 [CT-P13 IV]). W30/W54 clinical remission rates were comparable between arms. Other efficacy, safety, and immunogenicity assessments were also broadly comparable between arms, including after switching. CONCLUSIONS: The pharmacokinetic noninferiority of CT-P13 SC to CT-P13 IV, and the comparable efficacy, safety, and immunogenicity profiles, support the potential suitability of CT-P13 SC treatment in IBD. ClinicalTrials.gov ID: NCT02883452.

Real-world safety and efficacy of CT-P13, an infliximab biosimilar, in Japanese rheumatoid arthritis patients naïve to or switched from biologics.

OBJECTIVES: The aim of this post-marketing surveillance (PMS) study is to evaluate the real-world safety and efficacy of CT-P13, the first biosimilar of infliximab (IFX). METHODS: Japanese patients with rheumatoid arthritis were prospectively registered from November 2014 and followed up for 1 year. RESULTS: Of 794 patients in the analysis set, 318 patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) showed an immediate decrease in Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP) and increased remission rate (DAS28-CRP < 2.6). In patients who switched from IFX to CT-P13 for non-medical reasons (n = 374), the low DAS28-CRP due to previous IFX treatment decreased further with continued CT-P13 therapy. As in naïve patients, patients who switched from other bDMARDs, mainly for medical reasons (n = 102), responded similarly to CT-P13. CT-P13 in this PMS and IFX in a previous PMS had similar adverse reaction profiles, although the incidence rate in naïve patients in this current PMS was lower due to earlier initiation of CT-P13 therapy. CONCLUSIONS: CT-P13 showed excellent effectiveness as first-line therapy, no clinical difficulties in switching from IFX, and clinical improvement in patients who failed other bDMARDs. CT-P13 could be a cost-effective alternative to IFX in the treatment of rheumatoid arthritis.

Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial.

OBJECTIVE: To assess non-inferiority of s.c. to i.v. CT-P13 in RA. METHODS: Patients with active RA and inadequate response to MTX participated in this phase I/III double-blind study at 76 sites. Patients received CT-P13 i.v. 3 mg/kg [week (W) 0 and W2] before randomization (1:1) at W6 to CT-P13 s.c. via pre-filled syringe (PFS) 120 mg biweekly until W28, or CT-P13 i.v. 3 mg/kg every 8 weeks until W22. Randomization was stratified by country, W2 serum CRP and W6 body weight. From W30, all patients received CT-P13 s.c. In a usability sub-study, patients received CT-P13 s.c. via auto-injector (W46-54) then PFS (W56-64). The primary endpoint was change (decrease) from baseline in disease activity score in 28 joints (DAS28)-CRP at W22 (non-inferiority margin: -0.6). RESULTS: Of 357 patients enrolled, 343 were randomized to CT-P13 s.c. (n = 167) or CT-P13 i.v. (n = 176) at W6. The least-squares mean change (decrease) from baseline (standard error) in DAS28-CRP at W22 was 2.21 (0.22) for CT-P13 s.c. (n = 162) and 1.94 (0.21) for CT-P13 i.v. [n = 168; difference 0.27 (95% CI: 0.02, 0.52)], establishing non-inferiority. Efficacy findings were similar between arms at W54. Safety was similar between arms throughout: 92 (54.8%; CT-P13 s.c.) and 117 (66.9%; CT-P13 i.v.) patients experienced treatment-emergent adverse events (from W6). There were no treatment-related deaths or new safety findings. Usability was similar for CT-P13 s.c. via auto-injector or PFS. CONCLUSION: CT-P13 s.c. was non-inferior to CT-P13 i.v. in active RA. The convenience of s.c. administration could benefit patients. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT03147248.

Post-marketing analysis for biosimilar CT-P13 in inflammatory bowel disease compared with external data of originator infliximab in Japan.

BACKGROUND AND AIM: CT-P13, an infliximab (IFX) biosimilar, was approved for treatment of inflammatory bowel disease. However, no comparison with the originator IFX in this indication has been conducted in Japan where endemic levels of tuberculosis and hepatitis virus infection are not low. We evaluated the safety and efficacy in real-world data of CT-P13 and compared with originator IFX data in Japan. METHODS: In a prospective post-marketing surveillance (PMS) study, patients who received CT-P13 in a 28-month period from January 2015 were followed up for 2 years. By conducting Japanese administrative database search (DBS) for the same period of PMS, data of the originator IFX including treatment persistence, tuberculosis incidence, and liver injury were analyzed retrospectively and compared with the corresponding PMS data of CT-P13. RESULTS: CT-P13 persistence in PMS (n = 640) and IFX persistence in DBS (n = 4113) were almost similar between patients who switched from the originator and patients who continued on the originator, and also between the biologics-naïve patient groups. There were no differences in the incidences of tuberculosis and hepatic injury (Tuberculosis: 2 patients [0.31%] with CT-P13, 10 patients [0.24%] with the originator, P = 0.75; Hepatic injury: 18.5% with CT-P13, 15.4% with the originator, P = 0.22). Most of the patients with hepatic injury continued treatment in PMS and DBS at similar rates (80.8% vs 83.6%, P = 0.65). CONCLUSION: The results of long-term PMS of CT-P13 compared with external reference data from an administrative database suggested that the biosimilar and its originator were comparably useful in real-world clinical practice.

Does Similarity Breed Contempt? A Review of the Use of Biosimilars in Inflammatory Bowel Disease.

The introduction of therapeutic monoclonal antibodies directed against tumor necrosis factor-α has revolutionized the treatment of inflammatory bowel disease (IBD) by improving quality of life, decreasing the frequency and length of hospital admissions, and reducing corticosteroid use. Nevertheless, biologics are very expensive, substantially contributing to the cost of care for patients with IBD. To reduce this cost and improve treatment access, biosimilars, which are therapeutic monoclonal antibodies (biologicals) similar to but not identical to the reference biologic, were introduced. Despite their potential benefits, the adoption and uptake of biosimilars have varied considerably across the USA and Europe. Here, we highlight the current biosimilar therapeutic landscape, discuss barriers to their use, and provide an overview of published studies evaluating the efficacy and safety of biosimilars in IBD.

Systematic Review: Non-medical Switching of Infliximab to CT-P13 in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Biosimilar approval, such as Inflectra™ (CT-P13) for treating ulcerative colitis (UC) and Crohn's disease (CD), has reduced direct drug costs. Though clinicians are comfortable with biosimilar use in treatment-naïve patients, there are concerns in some jurisdictions that there are insufficient data from well-controlled trials to support non-medical switching. A systematic review, along with a critical assessment of the study design, was conducted to assess the potential impact of switching stable CD/UC patients from infliximab to CT-P13. METHODS: A literature search using PubMed and abstracts/posters from 3 major gastroenterology conferences from 2014 to 2018 was completed. Two individual reviewers extracted data from each relevant report and compiled it into evidence tables to facilitate descriptive analyses. Key randomized trial and observational study designs were critically assessed to contextualize data relevance. RESULTS: A total of 49 reports (3 randomized controlled trials, 40 observational trials, and 1 case series) were included. Most studies revealed no efficacy, safety, or immunogenicity concerns with non-medical switch. Limitations of supporting data include a small number of randomized controlled trials; predominance of observational studies with varying outcome assessments and lack of appropriate controls; and scarcity of research on biosimilar switch long-term effects. CONCLUSIONS: The majority of studies suggested non-medical switch is safe. However, clinicians and regulatory bodies should be aware of differences and limitations in study designs when making inferences about the risks and benefits of switching stable IBD patients to biosimilars.

Biosimilar infliximab in paediatric inflammatory bowel disease: Efficacy, immunogenicity and safety.

WHAT IS KNOWN AND OBJECTIVE: Based on extrapolation, biosimilar infliximab (IFX) was approved to treat inflammatory bowel disease (IBD). The first studies in adults have shown similar efficacy and safety in comparison with reference drug. The aim of this review was to collect and evaluate all the literature data regarding the use of biosimilar IFX in paediatric IBD. METHODS: This article reviewed efficacy, immunogenicity and safety profile of biosimilar IFX in IBD paediatric patients through a comprehensive search of the published literature. RESULTS AND DISCUSSION: Eight papers were extracted and critically reviewed. Four paediatric studies (prospective, n = 3; retrospective, n = 1) assessed the induction efficacy of the biosimilar IFX. Clinical response and remission rates reported were 86%-90% and 67%-68%, respectively. No significant difference in clinical response and remission rates between the reference and biosimilar IFX groups was found at follow-up (range: 3-13 months). Similar findings were shown in the prospective studies (n = 4) conducted on patients elected to switch from reference IFX to its biosimilar. The most frequently reported adverse events (AEs) of biosimilar IFX were mild upper respiratory tract infections. Taking into account of all AEs coming from published data, biosimilar IFX seems to be as safe as its originator. Immunogenicity has not been significantly impacted by the switch from the reference drug. WHAT IS NEW AND CONCLUSION: To date, treatment with (or switch to) biosimilar IFX in paediatric patients with IBD have been successful, without affecting efficacy, immunogenicity or safety. However, further studies are warranted, including clinical trials and pharmacovigilance studies.

Biosimilars in rheumatology.

Biotechnologicals are an invaluable resource in the treatment of patients with inflammatory rheumatic diseases (IRD) non-responsive or intolerant to conventional therapies. However, they are the main driver for increase in direct costs and represent a significant economic burden to healthcare systems worldwide. Since biosimilars are similar and more affordable versions of previously licenced biotechnologicals, they are expected to contribute to healthcare system sustainability and reduce inequities in treatment access. The landmark approval of CT-P13 as the first infliximab biosimilar paved the way for new infliximab but also etanercept, adalimumab and rituximab biosimilars. In Europe, North America and some countries of Asia, development is strictly regulated and only those presenting a totality-of-evidence dossier with highly similar physicochemical, biological and clinical performances are endorsed by regulatory agencies as biosimilars. The current article addresses the importance of biosimilar medicines in the treatment of IRD, as well as their innovative development and regulatory pathways, clinical evidence of similarity and challenges that may undermine their widespread use and success.

An updated systematic review and meta-analysis about the safety and efficacy of infliximab biosimilar, CT-P13, for patients with inflammatory bowel disease.

OBJECTIVE: We aimed to evaluate the efficacy and safety of infliximab biosimilar, CT-P13, for patients with inflammatory bowel disease. METHODS: We searched PubMed, Scopus, Ovid, and Web of Science for relevant clinical trials discussing CT-P31 administration for IBD patients either naïve to biological therapy or switched from IFX therapy. Data of the rates of clinical response, clinical remission, and adverse events were extracted and pooled in a random effect model meta-analysis using CMA version 2. RESULTS: Thirty-two studies with a total of 3464 IBD patients treated with CT-P13 were identified. The pooled rates of clinical response among Crohn's disease (CD) and ulcerative colitis (UC) at 8-14 weeks were 0.81 (95% CI = 0.72 to 0.87) and 0.68 (95% CI = 0.63 to 0.72), respectively, and at 48-63 weeks were 0.69 (95% CI = 0.48 to 0.85) and 0.54 (95% CI = 0.45 to 0.63) respectively. After switching from IFX to CT-P13, the pooled rates of sustained clinical response among CD and UC at 30-32 weeks were 0.84 (95% CI = 0.57 to 0.96) and 0.96 (95% CI = 0.58 to 0.99), respectively, and at 48-63 weeks were 0.51 (95% CI = 0.22 to 0.79) and 0.83 (95% CI = 0.19 to 0.99) respectively. Moreover, adverse events were reported (CD = 0.10, 95% CI 0.04 to 0.22; UC = 0.18, 95% CI 0.05 to 0.15). CONCLUSION: CT-P13 is effective and well tolerated in short and long-term periods. Switching to CT-P13 is recommended for the management of IBD.

Long-term efficacy and safety of CT-P13, a biosimilar of infliximab, in patients with inflammatory bowel disease: A retrospective multicenter study.

BACKGROUND AND AIM: A biosimilar of infliximab, CT-P13 (Remsima®) has the potential to reduce treatment costs and enhance access to biological therapy for inflammatory bowel disease (IBD) patients. However, long-term clinical data on its use for IBD treatment are currently sparse. We aimed to investigate the long-term efficacy and safety of CT-P13 therapy in a large, real-life IBD cohort. METHODS: A total of 368 IBD patients (227 with Crohn's disease [CD] and 141 with ulcerative colitis [UC]) treated with CT-P13 at 16 referral hospitals in Korea between July 2012 and December 2017 were retrospectively analyzed. RESULTS: The cumulative retention rates at years 1, 3, and 5 were 86.1%, 68.5%, and 58.7% and 69.7%, 46.0%, and 26.7% in anti-tumor necrosis factor (TNF)-naïve CD and UC patients, respectively. The clinical response and remission rates at week 14 and at years 1, 3, and 5 were 94.3%, 92.7%, 76.8%, and 17.6% and 78.6%, 82.4%, 72.2%, and 17.6% in anti-TNF-naïve CD and 85.6%, 80.0%, 55.2%, and 6.7% and 42.6%, 59.8%, 44.2%, and 6.7% in anti-TNF-naïve UC patients, respectively. Among patients who switched from the biologic originator to CT-P13, the cumulative retention rates at years 1, 3, and 5 were 88.5%, 66.1%, and 44.8% in CD, and 73.9%, 42.5%, and 42.5% in UC patients, respectively. Significant improvements in disease activity scores were accompanied by marked reductions in inflammatory marker levels, and no unexpected adverse events including death or malignancy occurred during the study period. CONCLUSIONS: Long-term treatment with CT-P13 is effective in inducing and maintaining disease improvement and is well-tolerated in patients with IBD. CT-P13 may be a promising treatment option for IBD.

Implementation of CT-P13 via a Managed Switch Programme in Crohn's Disease: 12-Month Real-World Outcomes.

BACKGROUND: Switching from Remicade to CT-P13 allows for significant cost savings and has been shown to be non-inferior to continued therapy with Remicade for the treatment of Crohn's disease. AIM: The aim of this work was to prospectively evaluate clinical outcomes in a cohort of patients with Crohn's disease switching from Remicade to CT-P13. METHODS: A prospective service evaluation was performed. The Harvey-Bradshaw index, CRP, faecal calprotectin and serum for infliximab/antibody levels were collected prior to patients' final Remicade infusion and at 6 and 12 months after switching to CT-P13 as part of routine clinical care. All adverse events during follow-up were also recorded. RESULTS: One hundred and ten patients on Remicade switched to CT-P13. No significant difference was observed between the Harvey-Bradshaw Index (p = 0.07), CRP (p = 0.13), faecal calprotectin (p = 0.25) or trough infliximab levels (p = 0.47) comparing before and at 6 and 12 months after the switch to CT-P13. Seven patients developed new infliximab antibodies after switching from Remicade to CT-P13. The majority of patients remained on CT-P13 at 12 months (84.5%) and the rate of adverse events and serious adverse events was 53.8 and 13.5 per 100 patient-years of follow-up, respectively. Switching to CT-P13 resulted in a cost saving of approximately 46.4%. CONCLUSION: The transition to CT-P13 from Remicade for the treatment of Crohn's disease is safe and has no negative effect on clinical outcomes at 12 months.

Efficacy and tolerability of initiating, or switching to, infliximab biosimilar CT-P13 in inflammatory bowel disease (IBD): a large single-centre experience.

OBJECTIVES: Recently, the infliximab biosimilar (CT-P13) received market authorisation for inflammatory bowel disease (IBD), allowing cost benefits when switching to CT-P13. We aim to assess the efficacy and safety of switching from originator infliximab to CT-P13 for new and existing patients. MATERIAL AND METHODS: Treatment response, remission, primary and secondary loss of response rates, and adverse events in patients who initiated infliximab originator in the 12 months pre-switch (n = 53) were compared with the patients who initiated CT-P13 in the 12 months post-switch (n = 69). Sustained responses were compared for existing infliximab originator patients who switched to CT-P13 (n = 191) and those who continued with the originator (n = 19). RESULTS: There was no difference in remission (58.1% vs. 47.4%, p = .37), response (12.6% vs. 10.5%, p = .80), secondary loss of response (24.6% vs. 42.1%, p = .10), or adverse events (4.7% vs. 0% p = 1.0) between those who switched to CT-P13 and those who continued infliximab originator. There was no difference in remission (42.0% vs. 26.4%, p = .074), response (21.7% vs. 22.6%, p = .91), primary non-response (5.8% vs. 15.1%, p = .09), secondary loss of response (21.7% vs. 22.6%, p = .91), or adverse events (8.7% vs. 11.3%, p = .63) in those who initiated CT-P13 compared with infliximab originator. CONCLUSIONS: There was no difference in the efficacy and safety of infliximab originator and CT-P13 during the first 12 months after switching.

Switching from an originator anti-TNF to a biosimilar in patients with inflammatory bowel disease: Can it be recommended? A systematic review.

AIM: To review the effectiveness and safety of switching from an originator anti-TNF (Remicade®) to a biosimilar (CT-P13) in patients with inflammatory bowel disease (IBD). METHODS: Electronic and manual search up to September 2017. RESULTS: We identified 24 studies evaluating switching between Remicade® and CT-P13 in 1326 patients. Disease control (no worsening after switching) was confirmed in most of the patients (weighted mean, 88%; 95% CI=86-89%). No unexpected adverse effects were reported in any of the studies. CONCLUSION: The risks of switching from Remicade® to a biosimilar seem to be purely theoretical and are not supported by the (still limited) real-world clinical practice experience. On the contrary, a steadily increasing number of publications have shown that there seem to be no safety or efficacy concerns about switching. Therefore, switching from originator to biosimilar infliximab in patients with IBD may be considered acceptable.

Biosimilars in rheumatology: A review of the evidence and their place in the treatment algorithm.

Determining biosimilarity involves a comprehensive exercise with a focus on determining the comparability of the molecular characteristics and preclinical profile of the biosimilar and reference product, such that there is less need for extensive clinical testing to assure comparability of clinical outcomes. Three anti-TNF biosimilar agents are approved for patients with rheumatic diseases in the European Union. The infliximab (Remicade®) biosimilars CT-P13 (Remsima® and Inflectra®) and SB2 (Flixabi®) and the etanercept (Enbrel®) biosimilar SB4 (Benepali®) have shown close comparability to their reference medicinal products, having undergone extensive evaluations. Guidelines on the treatment of rheumatic diseases have acknowledged that biosimilars and biologic DMARDs (bDMARDs) are interchangeable in clinical practice, except when patients experience lack of efficacy or tolerability with the reference agent. Given that cost is a barrier to effective bDMARD use, the introduction of less costly biosimilars is likely to widen access and dissipate treatment inequalities. Physicians faced with prescribing decisions should be reassured by the robust and exhaustive process that is involved in assuring comparability of biosimilars with their reference agents. De novo usage of a biosimilar and switching to a biosimilar following lack of efficacy or tolerability with a different reference biologic agent are likely to be strategies most easily adopted, although switching during successful treatment should also be considered given the potential cost implications. The introduction of biosimilar bDMARDs has the potential to improve patient access to effective biologic therapy, to better accommodate restraints within healthcare budgets and to improve overall patient outcomes.

Switching maintenance infliximab therapy to biosimilar infliximab in inflammatory bowel disease patients.

BACKGROUND: Clinical use of biosimilar infliximab (CT-P13) in inflammatory bowel diseases (IBDs) is based on extrapolation of indication from clinical studies performed in rheumatological diseases. Only few data exist of behaviour of infliximab trough levels (TLs) and anti-drug antibodies (ADAs) during switching. AIM: The objective of this study was to evaluate changes in TLs, ADA formation and disease activity after switching from originator infliximab to biosimilar one. METHODS: All our IBD patients receiving maintenance infliximab therapy were switched to biosimilar infliximab. TLs and ADAs were measured before the last originator infusion and before the third biosimilar infusion. Laboratory values, disease activity indices (partial Mayo score and Harvey-Bradshaw index) and demographic data were collected from patient records. RESULTS: A total of 62 patients were included in the final analysis (32 Crohn's disease, 30 ulcerative colitis (UC) or IBD-unclassified). No significant changes in median TLs before (5.5 mg/l) and after switching (5.5 mg/l, p = .05) occurred in the entire study group or in the Crohn's disease (CD) subgroup (5.75 and 6.5 mg/l, p = .68). However, in the subgroup of ulcerative colitis, the change in median TL was significantly different (from 5.2 to 4.25 mg/l, p = .019). Two patients developed ADAs after switching. No changes in disease activity were detected during switching and no safety concerns occurred. CONCLUSIONS: Switching from originator to biosimilar infliximab resulted in statistically significant differences in infliximab TLs in patients with UC but not in patients with Crohn's disease. The clinical significance for this difference is doubtful and in neither group changes in disease activity occurred.

Looking to the future and learning lessons from the recent past: changing stakeholder perceptions of biosimilars in cancer.

As the patents for many biologic anticancer drugs expire, significant growth in the use of biosimilars is predicted, offering an opportunity to help combat the rising costs of treatment and increase patient access to biologic therapy. Attainment of regulatory approval, involving numerous nonclinical and clinical comparative studies versus each reference product, is only one of several barriers to realize the potential gains offered by biosimilars. It is important to understand the current perceptions and informational needs of different stakeholders if biosimilars are to be accepted and widely used in the clinic. We discuss these considerations and refer to recent experiences with CT-P13, a biosimilar of the TNF inhibitor infliximab used to treat rheumatoid arthritis and other inflammatory disorders.

Effectiveness and Safety of CT-P13 (Biosimilar Infliximab) in Patients with Inflammatory Bowel Disease in Real Life at 6 Months.

BACKGROUND: CT-P13 is a biosimilar of Remicade®, an agent approved in some countries for use in inflammatory bowel disease (IBD). Controlled clinical trials have demonstrated the efficacy and safety of CT-P13 in rheumatic diseases, but not in IBD. AIMS: To assess the effectiveness and safety of CT-P13 in IBD patients in real clinical practice. METHODS: This is a prospective observational study in patients with moderate to severe Crohn's disease or ulcerative colitis treated with CT-P13. The study was performed in one single center. Patients included were naive or switched to anti-TNF treatment from the reference infliximab (Remicade®) to CT-P13. Efficacy and safety were assessed in naive and switched patients who were in remission at the time of the switch at months 3 and 6 of therapy. RESULTS: 87.5 and 83.9% of switched CD patients who were in remission at the time of the switch continued in remission, and 66.7 and 50% of naive CD patients reached remission, at months 3 and 6. In UC switched cases, 92 and 91.3% of patients in remission at the time of the switch continued in remission, at 3 and 6 months. In naive UC patients, the remission rates were 44.4 and 66.7%, at months 3 and 6. Adverse events occurred in 7.5% of patients during 6 months of study. CONCLUSIONS: CT-P13 was efficacious and well tolerated in patients with CD or UC.

Evolution after switching to biosimilar infliximab in inflammatory bowel disease patients in clinical remission. / Evolución tras el intercambio a infliximab biosimilar en pacientes con enfermedad inflamatoria intestinal en remisión clínica.

BACKGROUND AND AIM: The biosimilar of infliximab (CT-P13) has been approved for the same indications held by the infliximab reference product (Remicade®); however, there are few clinical data on switching in inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy, safety, bioavailability profile and factors associated with relapse after switching to biosimilar infliximab in IBD patients in clinical remission. MATERIAL AND METHOD: Observational study with IBD patients treated with Remicade® for at least 6 months and in clinical remission for at least 3 months who switched to infliximab biosimilar. The incidence of relapse, adverse effects and possible changes in drug bioavailability (trough level and antidrug antibodies) were evaluated. RESULTS: Thirty six patients were included (63.9% CD) with a mean follow-up of 8.4 months (SD±3.5). The 13.9% had clinical relapse. The longer clinical remission time before switching (HR=0.54, 95% CI=0.29-0.98, P=.04) and detectable infliximab levels at the time of switching (HR=0.03, 95% CI=0.001-0.89, P=.04) were associated with a lower risk of relapse. No differences were found between infliximab levels at the time of switching and at weeks 8 and 16 (P=.94); 8.3% of the patients had some adverse event, requiring the suspension of biosimilar in one patient for severe pneumonia. CONCLUSION: Switching to biosimilar infliximab in a real-life cohort of IBD patients in clinical remission did not have a significant impact on short-term clinical outcomes. The factors associated with relapse were similar to those expected in patients continuing with Remicade®.

Safety and efficacy of CT-P13 in Japanese patients with rheumatoid arthritis in an extension phase or after switching from infliximab.

OBJECTIVES: This study aimed to evaluate the safety of CT-P13 in patients with rheumatoid arthritis (RA) during long-term treatment or after switching from innovator infliximab (IFX). METHODS: Patients who completed 54 weeks of treatment in a phase I/II study (PI/II) received CT-P13 at an initial dose of 3 mg/kg at Week 62, with dose increases permitted up to 10 mg/kg. The primary endpoint was adverse event (AE) incidence. RESULTS: Thirty-four of 38 patients in the maintenance group and 29 of 33 in the switch group reported at least one AE. Safety profiles in both groups were similar to those in PI/II. Eleven of 28 patients who were positive for anti-drug antibodies (ADA) at Week 62 discontinued the study before Week 110. Forty-one of 43 ADA-negative patients remained negative, and 10 of 28 ADA-positive patients became negative during the study. The mean DAS28 (ESR) at Week 134 was 3.166 in the maintenance group and 3.955 in the switch group. CONCLUSIONS: CT-P13 was well tolerated in patients who maintained the treatment after 54 weeks and in patients who switched to CT-P13 after 54 weeks of IFX treatment. The study also demonstrated a stable clinical efficacy of CT-P13 in RA patients.