A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study
Multinationale Phase-III-Studie zu intravenösem Infliximab-Biosimilar bei rheumatoider Arthritis Vergleich zum Infliximab-Originator CT-P13 weist eine zum Referenz-Infliximab vergleichbare Wirksamkeit, Si...
A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study
A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study
Yoo DH et al.
Arthritis Res Ther. 2016; 18:82
Abstract
Background: CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®). The aim of this study was to compare the 54-week efficacy, immunogenicity, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of CT-P13 and RP in patients with active rheumatoid arthritis (RA).
Methods: In this multinational phase III double-blind study, patients with active RA and an inadequate response to methotrexate (MTX) were randomized (1:1) to receive CT-P13 (3 mg/kg) or RP (3 mg/kg) at weeks 0, 2, 6 and then every 8 weeks to week 54 in combination with MTX (12.5-25 mg/week). Efficacy endpoints included American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates, Disease Activity Score in 28 joints (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), European League Against Rheumatism (EULAR) response rates, patient-reported outcomes and joint damage progression. Immunogenicity, safety and PK/PD outcomes were also assessed.
Results: Of 606 randomized patients, 455 (CT-P13 233, RP 222) were treated up to week 54. At week 54, ACR20 response rate was highly similar between groups (CT-P13 74.7 %, RP 71.3 %). ACR50 and ACR70 response rates were also comparable between groups (CT-P13 43.6 % and 21.3 %, respectively; RP 43.1 % and 19.9 %, respectively). DAS28, SDAI and CDAI decreased from baseline to week 54 to a similar extent with CT-P13 and RP. Radiographic progression measured by Sharp scores as modified by van der Heijde was also comparable. With both treatments, patient assessments of pain, disease activity and physical ability, as well as mean scores on the Medical Outcomes Study Short Form Health Survey (SF-36), improved markedly at week 14 and remained stable thereafter up to week 54. The proportion of patients positive for antidrug antibodies at week 54 was similar between the two groups: 41.1 % and 36.0 % with CT-P13 and RP, respectively. CT-P13 was well tolerated and had a similar safety profile to RP. PK/PD results were also comparable between CT-P13 and RP.
Conclusions: CT-P13 and RP were comparable in terms of efficacy (including radiographic progression), immunogenicity and PK/PD up to week 54. The safety profile of CT-P13 was also similar to that of RP.
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Comparable long-term efficacy, as assessed by patient-reported outcomes, safety and pharmacokinetics, of CT-P13 and reference infliximab in patients with ankylosing spondylitis: 54-week results from the randomized, parallel-group PLANETAS study
Multinationale Phase-III-Studie zu intravenösem Infliximab-Biosimilar bei ankylosierender Spondylitis Vergleich zum Infliximab-Originator CT-P13 weist eine...
Comparable long-term efficacy, as assessed by patient-reported outcomes, safety and pharmacokinetics, of CT-P13 and reference infliximab in patients with ankylosing spondylitis: 54-week results from the randomized, parallel-group PLANETAS study
Comparable long-term efficacy, as assessed by patient-reported outcomes, safety and pharmacokinetics, of CT-P13 and reference infliximab in patients with ankylosing spondylitis: 54-week results from the randomized, parallel-group PLANETAS study
Park W et al.
Arthritis Res Ther. 2016; 18:25
Abstract
Background: CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®) and is approved in Europe and elsewhere, mostly for the same indications as RP. The aim of this study was to compare the 54-week efficacy, immunogenicity, pharmacokinetics (PK) and safety of CT-P13 with RP in patients with ankylosing spondylitis (AS), with a focus on patient-reported outcomes (PROs).
Methods: This was a multinational, double-blind, parallel-group study in patients with active AS. Participants were randomized (1:1) to receive CT-P13 (5 mg/kg) or RP (5 mg/kg) at weeks 0, 2, 6 and then every 8 weeks up to week 54. To assess responses, standardized assessment tools were used with an intention-to-treat analysis of observed data. Anti-drug antibodies (ADAs), PK parameters, and safety outcomes were also assessed.
Results: Of 250 randomized patients (n = 125 per group), 210 (84.0 %) completed 54 weeks of treatment, with similar completion rates between groups. At week 54, Assessment of Spondylo Arthritis international Society (ASAS)20 response, ASAS40 response and ASAS partial remission were comparable between treatment groups. Changes from baseline in PROs such as mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; CT-P13 -3.1 versus RP -2.8), Bath Ankylosing Spondylitis Functional Index (BASFI; -2.9 versus -2.7), and Short Form Health Survey (SF-36) scores (9.26 versus 10.13 for physical component summary; 7.30 versus 6.54 for mental component summary) were similar between treatment groups. At 54 weeks, 19.5 % and 23.0 % of patients receiving CT-P13 and RP, respectively, had ADAs. All observed PK parameters of CT-P13 and RP, including maximum and minimum serum concentrations, were similar through 54 weeks. The influence of ADAs on PK was similar in the two treatment groups. Most adverse events were mild or moderate in severity. There was no notable difference between treatment groups in the incidence of adverse events, serious adverse events, infections and infusion-related reactions.
Conclusions: CT-P13 and RP have highly comparable efficacy (including PROs) and PK up to week 54. Over a 1-year period, CT-P13 was well tolerated and displayed a safety profile comparable to RP; no differences in immunogenicity were observed.
Comparative Stability Studies of Different Infliximab and Biosimilar CT P13 Clinical Solutions by Combined Use of Physicochemical Analytical Techniques and Enzyme Linked Immunosorbent Assay (ELISA)
In-vitro Studie zum Vergleich der Stabilität von CT-P13 gegenüber Infliximab-Originator. Getestet wurden unterschiedliche Konzentrationen (0,4 mg/ml, 2 mg/ml und 10 mg/ml) bei verschiedenen Lagerungsbedi...
Comparative Stability Studies of Different Infliximab and Biosimilar CT P13 Clinical Solutions by Combined Use of Physicochemical Analytical Techniques and Enzyme Linked Immunosorbent Assay (ELISA)
Comparative Stability Studies of Different Infliximab and Biosimilar CT P13 Clinical Solutions by Combined Use of Physicochemical Analytical Techniques and Enzyme Linked Immunosorbent Assay (ELISA)
Hermosilla J et al.
BioDrugs (2019); 33: 193-205
Abstract
Background: There are two products in which infliximab is the active pharmaceutical ingredient. These are Remicade® (INF; reference product) and Remsima™/Inflectra™ (CT-P13; infliximab biosimilar). Remsima™/Inflectra™ are bioidentical
products. Different recommendations have been made for the clinical solutions of each brand (Remicade® or Remsima™/Inflectra™) despite the manufacturer of the biosimilar claiming high levels of similarity to the innovator. Objective The objective of this study was to assess and compare stability against degradation and over time of different clinical infliximab solutions prepared from Remicade® and from Remsima™/Inflectra™ using a suitable set of characterization methods in line with the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) recommendations.
Methods: Reconstituted solutions of INF and CT-P13 and dilutions as used in hospital were stored in glass vials (10 and 2 mg/mL) or in polyolefin infusion bags (0.4 mg/mL) refrigerated between 2 and 8 °C for 2 weeks. Regarding the physicochemical properties, the distribution of the particulates were studied over a range of 0.001–1 μm by dynamic light scattering (DLS) and oligomers up to 8 monomer were analyzed by native size-exclusion ultra-high-performance liquid chromatography with ultraviolet (UV)-visible detection coupled to (native) mass spectrometry (SE/UHPLC-UV-(native) MS); mass spectrometry was also used to evaluate natural aggregates and isoform profile; DLS was also employed to detect gross conformational
changes by tracking the hydrodynamic radius (HR). The secondary structure of the proteins was studied by far UV circular dichroism (CD). The tertiary structure was investigated by intrinsic tryptophan fluorescence (IT-F). Reverse-phase ultra-high-performance liquid chromatography with UV detection (RP/UHPLC-UV) was used to analyze intact INF and CT-P13 for quantification purposes. Functionality was evaluated via the biological activity measured by the extension of the immunological reaction of the INF and the CT-P13 with its antigen, i.e., the tumor necrosis factor-α by enzyme-linked immunosorbent assay (ELISA).
Results: The stress applied to INF and CT-P13 solutions showed similar levels of aggregate formation, structural variation, and chemical modifications. The only noteworthy difference between INF and CT-P13 was detected in their behavior to freeze–thaw cycles, in which CT-P13 showed slightly more robustness. INF and CT-P13 showed identical CD spectra, similar to those reported for IgG1 in which there is dominance in β sheet secondary structures; this typical conformation remained unmodified over time in INF and CT-P13. No significant changes were detected in the tertiary structure and no aggregates process was noticed over the time studied. Polydispersity slightly increased for the most concentrated solutions, while there were no meaningful differences in the HR in the solutions over time. The concentration of INF and CT-P13 also remained constant. Differences in the native isoform MS profile were detected, as expected by the different glycosylation pattern, with no important modification over time. Functionality was maintained over the test period (60 days) and was similar in all the solutions tested, with no differences between INF and biosimilar solutions.
Conclusions: High levels of similarity were noticed in the behavior of INF and CT-P13 when subjected to stress. When stored refrigerated at between 2 and 8 °C and prepared as normally used in the hospital pharmacy, all solutions showed physicochemical and functional stability for all the concentrations tested and all containers, at least for the 14-day test period.
One-month stability study of a biosimilar of infliximab (Remsima®) after dilution and storage at 4 °C and 25 °C
In-vitro-Untersuchung der Langzeit-Stabilität von CT-P13 IV Vergleich unter verschiedenen Lagerungsbedingungen und zu vorherigen Studienergebnissen zum Infliximab-Originator Diese Stabilitätsstudie zeigt nach Rekonstitution von CT-P13 IV in Wasser und Verdünnung in 0,9 % NaCl eine gleichb...
One-month stability study of a biosimilar of infliximab (Remsima®) after dilution and storage at 4 °C and 25 °C
One-month stability study of a biosimilar of infliximab (Remsima®) after dilution and storage at 4 °C and 25 °C
Viellard V et al.
Ann Pharm Fr. (2017);75(1):17-29
Summary There is currently only one monoclonal antibody for which there is a biosimilar: infliximab, which was released onto the French market in 2015. The SPC for the biosimilar (Remsima®) are superimposable on those of the original, including 24-hour stability at both 4 and 25 °C. The aim of our study was to determine the stability of this biosimilar during one month at 4 and 25 °C. Three different batches at two concentrations (0.7 mg/mL or 1.6 mg/mL) were used. Physicochemical stability was evaluated by the following methods: turbidity, UV spectrometry,
DLS, ion chromatography (CEX), gel exclusion chromatography (SEC), and light microscopy. The analyses were performed in triplicate. All methods used have been demonstrated to be valid for measuring antibody stability. There were no signs of physicochemical instability after seven days (on D7) of storage at 4 or 25 °C. From D15, we observed slight changes by ion (percentage distribution of the different isoforms) and gel exclusion chromatography (percentage distribution of different polymers, i.e. dimers, oligomers). However, the areas under the curves
were unchanged, and the proportions of polymers remained lower than 0.5 %. Tertiary structure analysis also showed a change from D15. All observed changes are consistent with progressive oligomerization by hydrophobic interactions. In conclusion, the reconstituted biosimilar is stable for seven days at 4 and 25 °C. Gradual oligomerization is observed from D15 but appearsto be less than 0.5 %, suggesting instability, albeit very limited, in the longer term; the practicalconsequences of this remain to be evaluated.
© 2016 Academie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.
Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study
Multizentrische, randomisierte, doppelblinde Phase-III-Studie zu intravenösem Infliximab-Biosimilar bei Morbus Crohn Vergleich zum Infliximab-Originator Im Vergleich mit dem Referenz-Infliximab wurde CT-P13 ei...
Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study
Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study
Ye BD et al.
Lancet. 2019; 293(10182):1699-1707
Abstract
Background: The infliximab biosimilar CT-P13 was approved for use in Crohn's disease after clinical comparison with originator infliximab in ankylosing spondylitis and rheumatoid arthritis; however, concerns about such indication extrapolation have been expressed. This study investigated whether CT-P13 is non-inferior to infliximab in patients with Crohn's disease who were naive to biological therapy.
Methods: In this randomised, multicentre, double-blind, phase 3 non-inferiority study, we enrolled patients with active Crohn's disease who had not responded to, or were intolerant to, non-biological treatments. Patients were randomly assigned (1:1:1:1) to receive CT-P13 then CT-P13, CT-P13 then infliximab, infliximab then infliximab, or infliximab then CT-P13, with switching occurring at week 30. Patients received 5 mg/kg CT-P13 or infliximab at weeks 0, 2, 6, and then every 8 weeks up to week 54. The primary endpoint was the proportion of patients with a decrease of 70 points or more in Crohn's Disease Activity Index (CDAI) from baseline to week 6. A non-inferiority margin of -20 % was set (CT-P13 was non-inferior to infliximab if the lower limit of the two-sided 95 % CI for the treatment difference was greater than -20). This trial is registered with ClinicalTrials.gov, number NCT02096861, and is completed.
Findings: Between Aug 20, 2014, and Feb 15, 2017, 308 patients were assessed for eligibility, and 220 patients were enrolled: 111 were randomly assigned to initiate CT-P13 (56 to the CT-P13-CT-P13 group and 55 to the CT-P13-infliximab group) and 109 to initiate infliximab (54 to the infliximab-infliximab group and 55 to the infliximab-CT-P13 group). CDAI-70 response rates at week 6 were similar for CT-P13 (77 [69.4 %, 95 % CI 59.9 to 77.8] of 111) and infliximab (81 [74.3 %, 95% CI 65.1 to 82.2] of 109; difference -4.9 % [95 % CI -16.9 to 7.3]), thereby establishing non-inferiority. Over the total study period, 147 (67 %) patients experienced at least one treatment-emergent adverse event (36 [64 %] in the CT-P13-CT-P13 group, 34 [62 %] in the CT-P13-infliximab group, 37 [69 %] in the infliximab-infliximab group, and 40 [73 %] in the infliximab-CT-P13 group).
Interpretation: This study showed non-inferiority of CT-P13 to infliximab in patients with active Crohn's disease. Biosimilar CT-P13 could be a new option for the treatment of active Crohn's disease.
Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial
Multizentrische randomisierte, doppelblinde Phase-IV-Studie zur Umstellung auf das Infliximab-Biosimilar CT-P13 bei Morbus Crohn, Colitis ulcerosa, Spondylarthritis, rheumatoider Arthritis und Psoriasis Nach ...
Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial
Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial
Jørgensen KK et al.
Lancet. 2017;389(10086):2304-2316
Abstract
Background: TNF inhibitors have improved treatment of Crohn's disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis, but are expensive therapies. The aim of NOR-SWITCH was to examine switching from originator infliximab to the less expensive biosimilar CT-P13 regarding efficacy, safety, and immunogenicity.
Methods: The study is a randomised, non-inferiority, double-blind, phase 4 trial with 52 weeks of follow-up. Adult patients on stable treatment with infliximab originator treated in a hospital setting for at least 6 months were eligible for participation. Patients with informed consent were randomised in a 1:1 ratio to either continued infliximab originator or to switch to CT-P13 treatment, with unchanged dosing regimen. Data were collected at infusion visits in 40 Norwegian study centres. Patients, assessors, and patient care providers were masked to treatment allocation. The primary endpoint was disease worsening during 52-week follow-up. 394 patients in the primary per-protocol set were needed to show a non-inferiority margin of 15 %, assuming 30 % disease worsening in each group. This trial is registered with ClinicalTrials.gov, number NCT02148640.
Findings: Between Oct 24, 2014, and July 8, 2015, 482 patients were enrolled and randomised (241 to infliximab originator, 241 to CT-P13 group; one patient was excluded from the full analysis and safety set for CT-P13) and 408 were included in the per-protocol set (202 in the infliximab originator group and 206 in the CT-P13 group). 155 (32 %) patients in the full analysis set had Crohn's disease, 93 (19 %) had ulcerative colitis, 91 (19 %) had spondyloarthritis, 77 (16 %) had rheumatoid arthritis, 30 (6 %) had psoriatic arthritis, and 35 (7 %) had chronic plaque psoriasis. Disease worsening occurred in 53 (26 %) patients in the infliximab originator group and 61 (30 %) patients in the CT-P13 group (per-protocol set; adjusted treatment difference -4.4 %, 95 % CI -12.7 to 3.9). The frequency of adverse events was similar between groups (for serious adverse events, 24 [10 %] for infliximab originator vs 21 [9 %] for CT-P13; for overall adverse events, 168 [70 %] vs 164 [68 %]; and for adverse events leading to discontinuation, nine [4 %] vs eight [3 %], respectively).
Interpretation: The NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 was not inferior to continued treatment with infliximab originator according to a prespecified non-inferiority margin of 15 %. The study was not powered to show non-inferiority in individual diseases.
Efficacy of subcutaneous vs intravenous infliximab in rheumatoid arthritis: a post-hoc analysis of a randomized phase III trial
Post-hoc-Analyse der randomisierten, doppelblinden, multizentrischen Phase-III-Studie zum Vergleich der subkutanen (SC) Applikation des monoklonalen IgG1-Antikörpers Infliximab mit der intravenösen (IV) Verabreichung bei Patienten mit rheumatoider Arthritis (RA) Vergleich ...
Efficacy of subcutaneous vs intravenous infliximab in rheumatoid arthritis: a post-hoc analysis of a randomized phase III trial
Efficacy of subcutaneous vs intravenous infliximab in rheumatoid arthritis: a post-hoc analysis of a randomized phase III trial
Constantin A et al.
Rheumatology. 2022; 00: 1–7
Abstract
Objectives: The primary endpoint of the pivotal phase III study of infliximab (IFX) s.c. demonstrated non-inferiority of s.c. to i.v. IFX, based on 28-joint DAS-CRP (DAS28-CRP) improvement at week (W) 22 (NCT03147248). This post-hoc analysis investigated whether numerical differences in efficacy outcomes at W30/54 were statistically significant, using conservative imputation methods.
Methods: Patients with active RA and inadequate response to MTX received IFX i.v. 3 mg/kg at W0 and W2 (induction) and were randomized (1:1) to IFX s.c. 120mg every 2 weeks or i.v. 3 mg/kg every 8 weeks thereafter (maintenance). Patients randomized to IFX i.v. switched to IFX s.c. from W30–54. This post-hoc analysis compared efficacy outcomes for s.c. and i.v. groups pre-switch (W30) and post-switch (W54) using last observation carried forward (LOCF) and non-responder imputation (NRI) methods.
Results: Of 343 randomized patients, 165 (IFX s.c.) and 174 (IFX i.v.) were analysed. At W30, significantly improved outcomes were identified with s.c. vs i.v. IFX for DAS28-CRP/DAS28-ESR/Clinical Disease Activity Index (CDAI)/Simplified Disease Activity Index (SDAI) scores (LOCF); ACR/good EULAR responses, DAS28-CRP/Boolean remission, and DAS28-CRP/DAS28-ESR/CDAI/SDAI low disease activity and remission (LOCF and/or NRI); and minimal clinically important difference in HAQ score (LOCF and NRI). After switching to IFX s.c. from IFX i.v., fewer significant between-group differences were identified at W54.
Conclusions: IFX s.c. showed improved efficacy at W30 compared with IFX i.v., and the reduced between-group difference in efficacy outcomes at W54 after switching supports the results suggesting benefits of IFX s.c. compared with IFX i.v. at W30. ClinicalTrials.gov ID: NCT03147248.
Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease
Phase-I-Studie zu subkutanem Infliximab bei CED Part 2: Morbus Crohn & Colitis ulcerosa. Vergleich zwischen Infliximab SC und Infliximab IV Die Daten belegen eine vergleichbare Sicherheit und Wirksamkeit bei den SC- und IV-Formulierungen von Infliximab. Auch ein Wechsel von IV zu...
Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease
Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease
Schreiber S et al.
Gastroenterology. 2021; 160(7):2231-2636.
Abstract
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.
Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial
Phase-I/III-Studie zu subkutanem Infliximab bei rheumatoider Arthritis Teil 2 Vergleich zwischen Infliximab SC und Infliximab IV Im Vergleich mit Infliximab IV wurde für Infliximab SC eine nicht unterlegene Wirksamkeit nachgewiesen und es wurden vergleichbare PK- u...
Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial
Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial
Westhovens R et al.
Rheumatology (Oxford). 2021 May 14;60(5):2277-2287.
Abstract
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.
A novel formulation of CT-P13 (infliximab biosimilar) for subcutaneous administration: 1-year result from a Phase I open-label randomised controlled trial in patients with active Crohn’s disease
Phase-I-Studie zu subkutanem Infliximab bei CED Teil 1: Morbus Crohn; primärer Endpunkt: Dosisfindung Vergleich zwischen Infliximab IV und Infliximab SC Die Ein-Jahres-Beobachtung bei Patienten mit aktivem ...
A novel formulation of CT-P13 (infliximab biosimilar) for subcutaneous administration: 1-year result from a Phase I open-label randomised controlled trial in patients with active Crohn’s disease
A novel formulation of CT-P13 (infliximab biosimilar) for subcutaneous administration: 1-year result from a Phase I open-label randomised controlled trial in patients with active Crohn’s disease
Reinisch W et al.
Journal of Crohn‘s and Colitis. 2019; 13(Suppl_1):S066-S067
Abstract
Background: Efficacy and safety of new subcutaneous (SC) formulation of CT-P13 (CT-P13 SC) up to Week 30 were comparable with intravenous (IV) formulation in both patients with Crohn’s disease1 (CD) and rheumatoid arthritis.2 The aim of this study was to report pharmacokinetics (PK), efficacy and overall safety of CT-P13 SC in patients with CD throughout the 1-year treatment period.
Methods: Patients with moderate-to-severe CD (CDAI score 220–450) were administered CT-P13 IV 5 mg/kg at Weeks 0 and 2, and randomised into four cohorts at Week 6. Cohort 1 received CT-P13 IV 5 mg/kg every 8 weeks and Cohorts 2–4 received CT-P13 SC 120 mg, 180 mg, and 240 mg, respectively, every 2 weeks up to Week 54. Blood samples were collected before study drug administration at each visit and drug levels were determined by electrochemiluminescent assay. Efficacy parameters of CDAI-70 response, clinical remission (CDAI<150), endoscopic response and remission, and overall safety were evaluated.
Results: In total, 44 patients were randomly assigned to 4 cohorts (1:1:1:1 ratio). Overall clinical response results were comparable between IV and SC cohorts after randomisation at Week 6 up to Week 30, whereas clinical remission appears to be numerically higher in the SC cohorts at Week 54. (Table 1). The mean Ctrough (pre-dose serum concentration of CT-P13 before next dose injection) in the SC cohorts throughout the study visits were higher than those of IV cohort after randomisation. Ctrough values increased with SC dose and were substantially greater than the target therapeutic concentration (5 μg/ml)3 throughout the study period (Figure 1). Safety profiles for CT-P13 SC cohorts were also comparable to the IV cohort. In total, injection site reactions were reported in 11.4% of the patients, but all cases were of Grade 1 or 2 in intensity (Table 1).
Conclusions: The results from 1-year treatment suggest similar effi cacyand safety of CT-P13 SC to CT-P13 IV. The mean serum concentration in all SC cohorts consistently exceeded the threshold of target therapeutic concentration. These results show that the novel SC formulation of CT-P13 may expand treatment options for use of infliximab biosimilar by providing high consistency in drug exposure during maintenance treatment.
References
1. Schreiber S, Jang BI, Borzan V, et al. Tu2018 – novelformulation of CT-P13 (infl iximab biosimilar) for subcutaneous administration: initial results from a Phase I open-label randomized controlled trial in patients with active Crohn’s disease. Gastroenterology 2018;154;S1371.
2. Westhovens R, Yoo DH, Jaworski J, et al. THU0191 – novel formulation of CT-P13 for subcutaneous administration in patients with rheumatoid arthritis: initial results from a phase I/III randomised controlled trial. Ann Rheum Dis 2018;77(Suppl 2).
3. Vaughn BP, Sandborn WJ, Cheifetz AS. Biologic concentration testing in inflammatory bowel disease. Inflamm Bowel Dis 2015;21:1435–42.
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FRI0128 A Novel Formulation of CT-P13 (Infliximab Biosimilar) For Subcutanous Administration: 1-Year Results from a Part 1 of Phase I/III Randomized Controlled Trial in Patients With Active Rheumatoid Arthritis
Phase-I/III-Studie zu subkutanem Infliximab bei rheumatoider Arthritis Part I Vergleich zwischen Infliximab SC und Infliximab IV CT-P13 zeigte eine vergleichbare Wirksamkeit und Sicherheit ...
FRI0128 A Novel Formulation of CT-P13 (Infliximab Biosimilar) For Subcutanous Administration: 1-Year Results from a Part 1 of Phase I/III Randomized Controlled Trial in Patients With Active Rheumatoid Arthritis
FRI0128 A Novel Formulation of CT-P13 (Infliximab Biosimilar) For Subcutanous Administration: 1-Year Results from a Part 1 of Phase I/III Randomized Controlled Trial in Patients With Active Rheumatoid Arthritis
Yoo DH et al.
Ann. Rheum. Dis. 2019; 78(Suppl_2)
Abstract
Background: Efficacy and safety of a new subcutaneous (SC) formulation (CT-P13 SC) up to Week 30 were comparable with intravenous (IV) formulation (CT-P13 IV) in both patients with rheumatoid arthritis (RA) [1] and Crohn's disease [2].
Objectives: This report is to further investigate pharmacokinetics, efficacy and overall safety of CT-P13 SC in patients with RA throughout the 1-year treatment period.
Methods: Patients with active RA (presence of 6 or more swollen and tender joints [of 28 assessed], and serum C-reactive protein [CRP] concentration >0.6 mg/dL) were treated with CT-P13 IV at Weeks 0 and 2, and were randomized for continuation with CT-P13 IV or SC administration at Week 6. The IV cohort received CT-P13 IV 3 mg/kg every 8 weeks and the SC cohorts received CT-P13 SC 90 mg, 120 mg or 180 mg, respectively, every 2 weeks up to Week 54. Pharmacokinetics blood samples were collected before study drug administration at each visit and drug levels were determined by electrochemiluminescent assay. Efficacy parameters including DAS28 and ACR criteria and overall safety were evaluated.
Results: A total of 50 patients were enrolled, of whom 48 patients were randomly assigned at Week 6 into 4 cohorts (1:1:1:1 ratio). The mean Ctrough (pre-dose serum concentration of CT-P13 before next dose injection) of SC cohorts throughout the study visits were higher than those of IV cohort after randomization at Week 6. Ctrough levels increased with SC dose and were sufficiently higher than the target therapeutic concentration (1 μg/mL) throughout the study period (Figure 1). Overall, the efficacy results of CT-P13 SC up to Week 54 were comparable to those of CT-P13 IV. Disease improvement by DAS28 (CRP) and ACR20 were comparable across all 4 cohorts, regardless of the route of administration or dosage of CT-P13 (Table 1). The safety profiles which occurred after study drug administration at Week 6 in SC cohorts were generally comparable to those of IV cohort and appeared similar to those previously reported for IV infliximab [3]. All injection site reactions were grade 1 or 2. No malignancy or death was reported (Table 1).
Conclusion: The results from 1-year treatment suggest similar efficacy and safety of CT-P13 SC to CT-P13 IV in RA. The mean serum concentration in all SC cohorts consistently exceeded the threshold of target therapeutic concentration. These results show that the novel SC formulation of CT-P13 may enhance treatment options for use of infliximab biosimilar by providing high consistency in drug exposure.
References
1 Westhovens et al., Annals of the Rheumatic Disease 2018;77:315.
2 Schreiber et al., Gastroenterology 2018;154(6):S-1371.
3 Yoo et al., Arthritis Research & Therapy 2016;18:82.
Nicht-interventionelle Studie: CT-P13 SC FERTIGPEN 1.0
In dieser multizentrischen, nicht-interventionellen Studie wurde bei Erwachsenen die Anwenderfreundlichkeit und Handhabung der subkutanen Anwendung des Infliximab-Pens evaluiert.
Nicht-interventionelle Studie: CT-P13 SC FERTIGPEN 1.0
Nicht-interventionelle Studie: CT-P13 SC FERTIGPEN 1.0
N.N.
Zusammenfassung Project no.: 20549
Dieser Pen enthält 120 mg Infliximab und wird alle zwei Wochen für die subkutane Injektion verwendet. Das untersuchte Präparat CT-P13 von Celltrion Healthcare ist eine subkutane Formulierung von Infliximab zur Injektion in Fettgewebe und zeigte zur IV-Formulierung eine vergleichbare Wirksamkeit und gleiches Sicherheitsprofil. Der chimäre monoklonale Antikörper der Klasse IgG1 bietet Patienten die Möglichkeit den Wirkstoff selbstständig subkutan zu applizieren und erweitert im Vergleich zur intravenösen Applikation die Optionen zur Verabreichung des Wirkstoffes, da dieser an diversen Stellen des Körpers injiziert werden kann.
Real-world Evidence for Subcutaneous Infliximab (CT-P13 SC) Treatment in Patients with Psoriatic Arthritis during the Coronavirus Disease (COVID-19) Pandemic: A Case Series
Fallstudie zur Umstellung auf subkutanes Infliximab bei Psoriasis-Arthritis Vergleich zwischen Infliximab SC und Infliximab IV Die Anwendung von CT-P13 SC bei Psoriasis-Arthritis ist nicht nur wirksam, sondern ermöglicht den Pat...
Real-world Evidence for Subcutaneous Infliximab (CT-P13 SC) Treatment in Patients with Psoriatic Arthritis during the Coronavirus Disease (COVID-19) Pandemic: A Case Series
Real-world Evidence for Subcutaneous Infliximab (CT-P13 SC) Treatment in Patients with Psoriatic Arthritis during the Coronavirus Disease (COVID-19) Pandemic: A Case Series
Baraliakos X et al.
Clinical Case Report. 2022;10(1)
Abstract
The COVID-19 pandemic highlighted the benefits of subcutaneous (SC) administration for healthcare systems. The first SC infliximab, CT-P13 SC, was safe and effective for the treatment of psoriatic arthritis. Observed patient preferences for continuing CT-P13 SC suggest that patients receiving IV infliximab should be offered a switch to CT-P13 SC.
Real-world Evidence for Subcutaneous Infliximab (CT-P13 SC) Treatment in Patients with Ankylosing Spondylitis during the Coronavirus Disease (COVID-19) Pandemic: A Case Series
Fallstudie zur Umstellung auf subkutanes Infliximab bei ankylosierender Spondylitis Vergleich zwischen Infliximab SC und Infliximab IV Die subkutane Darreichungsform des Infliximab-Biosimilars CT-P13 ermöglicht Patienten mit ...
Real-world Evidence for Subcutaneous Infliximab (CT-P13 SC) Treatment in Patients with Ankylosing Spondylitis during the Coronavirus Disease (COVID-19) Pandemic: A Case Series
Real-world Evidence for Subcutaneous Infliximab (CT-P13 SC) Treatment in Patients with Ankylosing Spondylitis during the Coronavirus Disease (COVID-19) Pandemic: A Case Series
Vijayan S et al.
Clinical Case Report. 2022;10(1)
Abstract
The COVID-19 pandemic emphasized the utility of subcutaneous (SC) biologics for pressured healthcare systems. The first SC form of infliximab, CT- P13 SC, provided safe and effective treatment for ankylosing spondylitis in our case series, with increased convenience relative to intravenous treatment benefitting patients both during the pandemic and beyond.
Efficacy and safety of elective switching of inflammatory bowel disease patients from intravenous to subcutaneous infliximab (IFX): a multi-centre cohort study
Retrospektive multizentrische Kohortenstudie zur Umstellung auf subkutanes Infliximab bei CED Vergleich Ansprechen vor und nach dem Switch von Infliximab IV auf Infliximab SC Patienten mit chronisch-entzündlichen Darmerkrankungen weisen nac...
Efficacy and safety of elective switching of inflammatory bowel disease patients from intravenous to subcutaneous infliximab (IFX): a multi-centre cohort study
Efficacy and safety of elective switching of inflammatory bowel disease patients from intravenous to subcutaneous infliximab (IFX): a multi-centre cohort study
Smith PJ et al.
J. Crohns Colitis. 2021; 15(Suppl_1):480-481
Abstract
Background: A subcutaneous (SC) formulation of IFX has recently been shown to be as effective as intravenous (IV) IFX in a randomised trial but there are no real world data to support elective switching. We aimed to assess the effectiveness of an elective switching program from IV to SC IFX in patients with IBD.
Methods: Patients on maintenance IV IFX were included in this retrospective multi-centre cohort study across two sites. Disease activity was monitored serially with Harvey-Bradshaw Index (HBI) and simple clinical colitis activity index (SCCAI) at baseline, 3 and 6 months. Faecal calprotectin (FCP), C-reactive protein (CRP) and IFX levels were recorded at the same time points. Patients on 5mg/kg every 8 weeks were switched to SC IFX 120mg every other week (EOW), followed by those on 6 and 4 weekly IV IFX to either EOW or weekly SC IFX. A random selection of patients were surveyed for patient satisfaction using a likert scale. Criteria for switching were agreed within a standard operating procedure. Data was analysed using SPSS for Windows with p<0.05 being significant (ns, non-significant).
Results: 172 patients (109 CD, 57 UC, 6 IBD-U) were switched to SC IFX since April 2020 (97 male vs. 75 female; mean age 39.7 years and weight 78.6kg). 57.6% patients (n=99) were on concurrent immunomodulators. 152 patients were switched to EOW dosing. From baseline to 6 months post switch, HBI, SCCAI, FCP and CRP remained stable (p>0.05, ns), but mean IFX levels significantly increased from baseline (baseline = 9.8ug/mL vs. 3 month = 14.6ug/mL; p<0.0001) and then levels remained high between 3 and 6 month follow up (6 month = 15.0ug/mL; p>0.05, ns). 8 patients (4.65%) had self-limiting skin injection site reactions, 1 UC patient (0.58%) required corticosteroids, and 2 patients (1.16%) developed perianal symptoms requiring examination under anaesthesia (EUA). Overall 4 patients (2.36%) discontinued SC treatment due to adverse events (2 perianal disease patients, 1 flaring UC patient requiring oral steroids and 1 patient with neurological symptoms) and 1 (0.58%) planned discontinuation for a patient in the 3rd trimester of pregnancy. 85.2% (75/88) of patients agreed they were happier on SC IFX compared to IV IFX, 88.6% (78/88) feeling at least the same or better on SC IFX, and 92% (81/88) and 86.4% (76/88) agreeing that SC IFX was easy to use and felt safe using it, respectively.
Conclusion: SC IFX is effective at maintaining remission in IBD patients switched from IV to SC IFX with no evidence of inferiority at 6 month follow up. There is a significant increase in IFX levels from baseline to 3 months which is maintained to 6 months post switch. SC IFX appears to be safe with low rates of adverse events and is well tolerated by patients.
Efficacy of subcutaneous Infliximab in perianal Crohn’s Disease
Retrospektive Beobachtungsstudie zur Umstellung auf subkutanes Infliximab bei perianalen Fisteln bei Morbus Crohn Patienten mit perianalen Fisteln bei Morbus Crohn unter Erhaltungstherapie mit Infliximab zeigen nach einem Wechsel von einer intravenösen zu einer subkutanen Verabreichung eine hohe Rate an Symptomfreiheit und weisen eine ...
Efficacy of subcutaneous Infliximab in perianal Crohn’s Disease
Efficacy of subcutaneous Infliximab in perianal Crohn’s Disease
Smith PJ et al.
UEG Journal. 2021; 9(8):526
Abstract
Introduction: A new subcutaneous (SC) formulation of infliximab has recently been approved for the management of inflammatory bowel diseases (IBD). In the registration clinical trial, the efficacy of SC IFX was comparable to intravenous (IV) IFX (1) but specific data regarding the efficacy of SC IFX in perianal Crohn’s disease (pCD) is lacking. We aimed to investigate the efficacy of SC IFX in patients with pCD who were switched from IV IFX.
Aims & Methods: We conducted a single centre observational, retrospective study of pCD patients who were maintained on IV IFX and switched to SC IFX. Elective switching was at the discretion of the treating physician. In patients with active pCD at treatment initiation, the success of SC IFX was defined by clinical success at 6 months assessed by the physician’s judgment without additional medical or surgical treatment for pCD. In patients with inactive pCD, the pCD recurrence-free survival was calculated. Treatment persistence rates were calculated at the end of 6 months. Safety and adverse events of interest were recorded. Data was analysed using SPSS for Windows with p<0.05 being significant.
Results: We included 18 patients with a mean age of 36 (SD 12) and a M:F ratio of 5:4. Eleven (61%) patients were on concomitant thiopurines with a mean 6-thioguanine level of 258 (SD 155). The majority (n=13, 72%) had an intersphincteric fistula, 1 patient had a supra-sphincteric fistula (5.6%) and 2 patients (11.1%) each had trans-sphincteric and extra-sphincteric fistulae respectively. None of the patients had active, draining fistulae at the time of switching and 1 patient had an examination under anaesthesia (EUA) in the 6 weeks prior to switch. The mean IFX level at baseline was 9.9 mg/ml (SD 4.1). Two patients (11.1%) had recurrence of symptoms after switching to SC IFX and required further antibiotic therapy and EUA. These two patients also switched back to IV IFX after a median of 2.25 months. The mean IFX levels at 3 and 6 months after switch were 15.6 mg/ml (SD 0.2) and 15.5 mg/ml (SD 1.4) respectively (P<0.01, compared to baseline). The treatment persistence rate at 6 months post switch was 89% (16/18). There were no safety issues or adverse events of note.
Conclusion: Patients with pCD who were switched from IV to SC IFX had a high rate of symptom free survival and treatment persistence at 6 months. Treatment switch was associated with an increase in IFX levels. The efficacy of SC IFX at 6 months appears comparable to IV IFX for maintenance of remission in pCD (2).
References
1. Schreiber S, Ben-Horin S, Leszczyszyn J, Dudkowiak R, Lahat A, Gawdis-Wojnarska B, Pukitis A, Horynski M, Farkas K, Kierkus J, Kowalski M, Lee SJ, Kim SH, Suh JH, Kim MR, Lee SG, Ye BD, Reinisch W. Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease. Gastroenterology. 2021 Mar 5:S0016-5085(21)00474-1.
2. Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004 Feb 26;350(9):876-85
Comparison of combination subcutaneous Infliximab and an Immunomodulator versus subcutaneous Infliximab Monotherapy: Post-hoc Analysis of a randomised clinical trial
Post-hoc-Analyse zu subkutanem Infliximab in Mono- bzw. Kombinationstherapie bei Morbus Crohn und Colitis ulcerosa Vergleich zwischen der Monotherapie mit Infliximab SC und der Kombinationstherapie mit Immunmodulatoren Eine subkutane M...
Comparison of combination subcutaneous Infliximab and an Immunomodulator versus subcutaneous Infliximab Monotherapy: Post-hoc Analysis of a randomised clinical trial
Comparison of combination subcutaneous Infliximab and an Immunomodulator versus subcutaneous Infliximab Monotherapy: Post-hoc Analysis of a randomised clinical trial
D’Haens GR et al.
United European Gastroenterology Journal. 2021; 9(8):549
Abstract
Introduction: Infliximab (IFX) combination therapy with immunomodulators improves outcomes versus IFX monotherapy in naïve patients (pts) with early Crohn’s disease (CD);¹ however knowledge on subcutaneous (SC) IFX is lacking. A pivotal randomised controlled trial (NCT02883452) evaluated the SC IFX, CT-P13 SC, in active CD or ulcerative colitis (UC).²
Aims & Methods: This post-hoc analysis evaluated the comparative efficacy of SC IFX monotherapy versus combination therapy with immunomodulators using data from the pivotal trial. Pts with active UC or CD who were tumour necrosis factor (TNF) inhibitor naïve were enrolled and received induction therapy with CT-P13 5 mg/kg intravenously (IV) at Week (W) 0 and W2, after which they were randomised to continue therapy with IV CT-P13, or receive CT-P13 SC 120 mg (pts <80 kg) or 240 mg (pts ≥80 kg) every 2 weeks from W6–54. Pts were stratified by current use of immunomodulators such as azathioprine, 6-mercaptopurine or methotrexate at W6 randomisation.2 For this analysis, only pts in the SC arm were investigated. The following outcomes were compared at W54 between pts receiving combination CT-P13 SC monotherapy and those receiving CT-P13 SC with an immunomodulator: trough serum concentration (Ctrough; 5 μg/mL was the target exposure level), clinical response (for CD pts, ≥100-point decrease in Crohn’s Disease Activity Index score; for UC pts, ≥2-point decrease in partial Mayo score with accompanying ≥1 point decrease in rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1) and immunogenicity (anti-drug antibody [ADA] and neutralising antibody [NAb] positivity; as measured by a drug tolerant assay; ADA negative was regarded as NAb negative). Statistical comparisons used Fisher’s exact test. The differences are reported in a descriptive manner.
Results: Of 66 pts in the CT-P13 SC arm, 37 and 29 received monotherapy and combination therapy, respectively. Mean age was 37.9 years (monotherapy) and 37.7 years (combination therapy); mean disease durationwas 5.3 years (monotherapy) and 6.2 years (combination therapy). Pts with available data at W54 were included in this analysis (Table). There was no significant difference between groups in the number of pts with a Ctrough level exceeding target exposure (monotherapy: 28/29; combination therapy: 23/24; p>0.999). Median (interquartile range) Ctrough (μg/mL) was 20.80 (16.10–29.10) and 21.65 (18.98–25.25) for monotherapy and combination therapy, respectively. Clinical response rates were also comparable (monotherapy: 26/35; combination therapy: 23/27; p=0.3582). Moreover, there were no differences in immunogenicity between groups despite the concomitant use of immunomodulators in the combination group (Table; p=0.2711 for ADA positivity; p=0.3987 for NAbs).
Conclusion: In TNF inhibitor naïve pts with active CD or UC, SC IFX monotherapy may provide comparable clinical efficacy to combination therapy with immunomodulators, but larger comparative studies are warranted.
References
1. Cosnes J, et al. Adalimumab or infliximab as monotherapy, or in combination with an immunomodulator, in the treatment of Crohn’s disease. Aliment Pharmacol Ther 2016;44:1102–13.
2. Schreiber S, et al. Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease. Gastroenterology 2021; S0016-5085(21)00474-1.
Switching from intravenous to subcutaneous Infliximab in patients with active inflammatory bowel disease: Post-hoc Analysis of pre/post switch outcomes from a multicentre, randomised controlled pivotal trial
Post-hoc-Analyse der Pivotstudie zur Umstellung auf subkutanes Infliximab bei Morbus Crohn und Colitis ulcerosa Vergleich zwischen Infliximab SC und Infliximab IV Die Umstellung einer intravenö...
Switching from intravenous to subcutaneous Infliximab in patients with active inflammatory bowel disease: Post-hoc Analysis of pre/post switch outcomes from a multicentre, randomised controlled pivotal trial
Switching from intravenous to subcutaneous Infliximab in patients with active inflammatory bowel disease: Post-hoc Analysis of pre/post switch outcomes from a multicentre, randomised controlled pivotal trial
Schreiber S et al.
United European Gastroenterology Journal. 2021; 9(8):553-554
Abstract
Introduction: A subcutaneous (SC) infliximab (IFX), CT-P13 SC, has received regulatory approval from the European Medicines Agency for indications including inflammatory bowel disease.¹ In response to the coronavirus disease 2019 (COVID-19) pandemic, clinical guidance has recommended considering switching from intravenous (IV) treatment to SC alternatives to minimise hospital visits.²
Aims & Methods: In this analysis, data from the pivotal randomised controlled trial (NCT02883452) of CT-P13 SC in patients with active Crohn’s disease (CD) and ulcerative colitis (UC) were analysed to investigate the clinical impact of switching from IV to SC IFX.3 Patients in the CT-P13 IV arm of the pivotal trial received CT-P13 5 mg/kg IV every 8 weeks from Week (W) 6 until W22. At W30, patients switched to receive CT-P13 SC every 2 weeks up to W54 (dose 120 mg or 240 mg for patients <80 kg or ≥80 kg, respectively).³
This post hoc analysis compared per-patient pairwise data at W30 (pre-switch) and W54 (post-switch) from the CT-P13 IV arm for the following outcomes: trough serum concentration (Ctrough; 5 μg/mL was considered to be the target exposure level), clinical response (for CD patients, ≥100-point decrease in Crohn’s Disease Activity Index score; for UC patients, ≥2-point decrease in partial Mayo score with accompanying ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1) and immunogenicity (anti-drug antibody [ADA] and neutralising antibody [NAb] positivity; as measured by a drug tolerant assay; ADA negative was regarded as NAb negative). For pairwise comparisons, patients with missing data at either W30 or W54 were excluded from the analysis. Statistical comparisons used Fisher’s exact test. The differences are reported in a descriptive manner.
Results: Overall, 65 patients (25 CD; 40 UC) were included in the CT-P13 IV
arm. The proportion of patients with a Ctrough level exceeding target exposure was significantly higher post-switch (36/41, 87.8%) than pre-switch (8/41, 19.5%; p<0.00001) (Table). Clinical response rates were comparable at both pre- and post-switch timepoints (40/49 [81.6%] vs 44/49 [89.8%], respectively; p=0.3873). Positive ADA and NAb rates at pre-switch and post-switch were also comparable, in which some changes were regarded from patients with marginal value (Table).
Conclusion: Switching from IV to SC IFX did not detrimentally affect the clinical outcomes of patients with active CD or UC. Further, switching from IV to SC IFX might confer more favourable pharmacokinetic outcomes, although larger comparative studies are warranted.
References
1. European Medicines Agency. Remsima summary of product characteristics. 2021. https://www.ema.europa.eu/en/documents/product-information/remsima-epar-product-information_en.pdf [accessed 23 April 2021].
2. Magro F, et al. Inflammatory Bowel Disease Management During the COVID-19 Outbreak: The Ten Do’s and Don’ts from the ECCO-COVID Taskforce. J Crohns Colitis 2020;14(Suppl. 3):S798–S806.
3. Schreiber S, et al. Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease. Gastroenterology. 2021; S0016-5085(21)00474-1.
Efficacy and Safety of elective Switching of Inflammatory Bowel Disease Patients from intravenous to subcutaneous Infliximab: A multi-centre Cohort Study
Multizentrische Kohortenstudie zur Umstellung auf subkutanes Infliximab bei CED Vergleich der Wirksamkeit von Infliximab SC und Infliximab IV 6 Monate nach Umstellung von intravenösem auf subkutanes Infliximab in der Erhaltungstherapie zeigt ein h...
Efficacy and Safety of elective Switching of Inflammatory Bowel Disease Patients from intravenous to subcutaneous Infliximab: A multi-centre Cohort Study
Efficacy and Safety of elective Switching of Inflammatory Bowel Disease Patients from intravenous to subcutaneous Infliximab: A multi-centre Cohort Study
Smith PJ et al.
United European Gastroenterology Journal. 2021; 9(8):117
Abstract
Introduction: A subcutaneous (SC) formulation of infliximab (IFX) has recently been shown to be as effective as intravenous (IV) IFX in a randomised trial (1) but there are no real world data to support elective switching.
Aims & Methods: We aimed to assess the effectiveness of an elective switching program from IV to SC IFX. Patients on maintenance IV IFX were included in this retrospective multi-centre cohort study across two sites. Disease activity was monitored serially with Harvey-Bradshaw Index (HBI) and simple clinical colitis activity index (SCCAI) at baseline, 3 and 6 months. Faecal calprotectin (FCP), C-reactive protein (CRP) and IFX levels were recorded at the same time points. Patients on 5mg/kg every 8 weeks were switched to SC IFX 120mg every other week (EOW), followed by those on 6 and 4 weekly IV IFX to either EOW or weekly SC IFX. A random selection of patients were surveyed for patient satisfaction using a likert scale. Criteria for switching were agreed within a standard operating procedure. Data was analysed using SPSS for Windows with p<0.05 being significant (ns, non-significant).
Results: 172 patients (109 CD, 57 UC, 6 IBD-U) were switched to SC IFX since April 2020 (97 male vs. 75 female; mean age 39.7 years and weight 78.6kg). 57.6% patients (n=99) were on concurrent immunomodulators. 152 patients were switched to EOW dosing. From baseline to 6 months post switch, HBI, SCCAI, FCP and CRP remained stable (p>0.05, ns), but mean IFX levels significantly increased from baseline (baseline = 9.8ug/mL vs. 3 month = 14.6ug/mL; p<0.0001) and then levels remained high between 3 and 6 month follow up (6 month = 15.0ug/mL; p>0.05, ns). 8 patients (4.65%) had self-limiting skin injection site reactions, 1 UC patient (0.58%) required corticosteroids, and 2 patients (1.16%) developed perianal symptoms requiring examination under anaesthesia (EUA). Overall 4 patients (2.36%) discontinued SC treatment due to adverse events (2 perianal dis - ease patients, 1 flaring UC patient requiring oral steroids and 1 patient with neurological symptoms) and 1 (0.58%) planned discontinuation for a patient in the 3rd trimester of pregnancy. 85.2% (75/88) of patients agreed they were happier on SC IFX compared to IV IFX, 88.6% (78/88) feeling at least the same or better on SC IFX, and 92% (81/88) and 86.4% (76/88) agreeing that SC IFX was easy to use and felt safe using it, respectively.
Conclusion: SC IFX is effective at maintaining remission in IBD patients switched from IV to SC IFX with no evidence of inferiority at 6 month follow up. There is a significant increase in IFX levels from baseline to 3 months which is maintained to 6 months post switch. SC IFX appears to be safe with low rates of adverse events and is well tolerated by patients.
References
Schreiber S, Ben-Horin S, Leszczyszyn J, Dudkowiak R, Lahat A, Gawdis-Wojnarska B, Pukitis A, Horynski M, Farkas K, Kierkus J, Kowalski M, Lee SJ, Kim SH, Suh JH, Kim MR, Lee SG, Ye BD, Reinisch W. Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13
Maintenance in Inflammatory Bowel Disease. Gastroenterology. 2021 Mar 5:S0016-5085(21)00474-1.
CT-P13 Subcutaneous Infliximab in Gastroenterology and Rheumatology
Biosimilars erweitern Therapiemöglichkeiten und erleichtern den Zugang zu diesen. Subkutanes Infliximab bietet eine hohe Flexibilität für Patienten und verringert Krankenhausaufenthalte. Klinische Studien in der Rheumatologie und der Gastroenterologie betrachten neben den pharmakodynamischen und pharmakokinetischen Daten auch Siche...
CT-P13 Subcutaneous Infliximab in Gastroenterology and Rheumatology
CT-P13 Subcutaneous Infliximab in Gastroenterology and Rheumatology
Ahmed M et al.
Immunotherapy. 2021;13(12):1001-1009
Abstract
The drug infliximab has been a key milestone in the treatment of inflammatory conditions such as Crohn's disease, ulcerative colitis, rheumatoid arthritis and the seronegative spondyloarthritides. Biosimilar drugs followed the originator, further improving access and diversity of therapy choice. Subcutaneous infliximab (CT-P13) holds potential for greater patient flexibility by self administration, reducing travel and hospital attendance for infusion, particularly relevant at a time of pandemic. We highlight the pharmacodynamic and pharmacokinetic basis of the subcutaneous device, clinical trials in rheumatology and gastroenterology and consider the safety and cost implications. Real-world switching data is required to confirm the efficacy data from clinical trials given the reduction in dosing flexibility compared with intravenous therapy.
Innovative approaches to biologic development on the trail of CT-P13: biosimilars, value-added medicines, and biobetters
Innovative Biologika wie CT-P13 SC zeigen im Vergleich zu intravenös angewendeten Präparaten vergleichbare Ergebnisse beim Wirk- und Sicherheitsprofil und der Immunogenität auf. Sie bieten einen zusätzlichen Nutzen, da die häusliche Anwendung für viele Patienten praktikabler ist ...
Innovative approaches to biologic development on the trail of CT-P13: biosimilars, value-added medicines, and biobetters
Innovative approaches to biologic development on the trail of CT-P13: biosimilars, value-added medicines, and biobetters
Kim H et al.
mAbs. 2021;13(1)
Abstract
The biosimilar concept is now well established. Clinical data accumulated pre- and post-approval have supported biosimilar uptake, in turn stimulating competition in the biologics market and increasing patient access to biologics. Following technological advances, other innovative biologics, such as "biobetters" or "value-added medicines," are now reaching the market. These innovative biologics differ from the reference product by offering additional clinical or non-clinical benefits. We discuss these innovative biologics with reference to CT-P13, initially available as an intravenous (IV) biosimilar of reference infliximab. A subcutaneous (SC) formulation, CT-P13 SC, has now been developed. Relative to CT-P13 IV, CT-P13 SC offers clinical benefits in terms of pharmacokinetics, with comparable efficacy, safety, and immunogenicity, as well as increased convenience for patients and reduced demands on healthcare system resources. As was once the case for biosimilars, nomenclature and regulatory pathways for innovative biologics require clarification to support their uptake and ultimately benefit patients.
Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week randomized, double-blind study in rheumatoid arthritis
Phase-III-Studie zu citratfreiem und volumenreduzierten Adalimumab bei rheumatoider Arthritis Vergleich zwischen Adalimumab-Biosimilar und -Originator Datenauswertung nach 52 Wochen Das Adalimumab-Biosimilar entspricht bei Patienten mit rheumatoider Arthri...
Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week randomized, double-blind study in rheumatoid arthritis
Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week randomized, double-blind study in rheumatoid arthritis
Furst DE et al.
Rheumatology 2021;0:1–11
Abstract
Objective: To compare the safety and efficacy of switching from reference adalimumab to adalimumab biosimilar CT-P17 with continuing reference adalimumab/CT-P17 in active RA.
Methods: This double-blind, phase III study randomized (1:1) subjects with active RA to receive 40 mg (100 mg/ml) CT-P17 or European Union-sourced reference adalimumab subcutaneously every 2 weeks (Q2W) until week (W) 24 [treatment period (TP) 1]. Thereafter, subjects receiving reference adalimumab were randomized (1:1) to continue reference adalimumab or switch to CT-P17 from W26 (both Q2W until W48; TP2). Subjects receiving CT-P17 in TP1 continued CT-P17. W0–W24 results were previously reported; we present W26–W52 findings. End points were efficacy (including joint damage progression), pharmacokinetics, safety and immunogenicity.
Results: Of 607 subjects who initiated TP2 treatment, 303 continued CT-P17, 153 continued reference adalimumab and 151 switched to CT-P17. Efficacy improvements up to W24 were maintained during TP2; efficacy was comparable among groups. At W52, 20% improvement in ACR response rates were 80.5% (continued CT-P17), 77.8% (continued reference adalimumab) and 82.2% (switched to CT-P17). Joint damage progression was minimal. Mean trough serum adalimumab concentrations were similar among groups. CT-P17 and reference adalimumab safety profiles were numerically similar and switching did not affect immunogenicity. At W52, 28.4% (continued CT-P17), 27.0% (continued reference adalimumab) and 28.3% (switched to CT-P17) of subjects were anti-drug antibody-positive.
Conclusion: Efficacy, pharmacokinetics, safety and immunogenicity of CT-P17 and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to CT-P17.
Weiterlesen
Efficacy and safety of biosimilar CT-P17 versus reference adalimumab in subjects with rheumatoid arthritis: 24-week results from a randomized study
Phase-III-Studie zu citratfreiem und volumenreduzierten Adalimumab bei rheumatoider Arthritis Vergleich zwischen Adalimumab-Biosimilar und -Originator Datenauswertung nach 24 Wochen Das Adalimumab-Biosimilar entspricht bei Patienten mit rheumatoider Art...
Efficacy and safety of biosimilar CT-P17 versus reference adalimumab in subjects with rheumatoid arthritis: 24-week results from a randomized study
Efficacy and safety of biosimilar CT-P17 versus reference adalimumab in subjects with rheumatoid arthritis: 24-week results from a randomized study
Kay J et al.
Arthritis Res. Ther. 2021; 23 (Article no.51).
Abstract
Background: To demonstrate equivalent efficacy of the proposed high-concentration (100 mg/ml), citrate-free adalimumab biosimilar CT-P17 to European Union-approved adalimumab (EU-adalimumab) in subjects with active rheumatoid arthritis (RA).
Methods: This randomized, double-blind phase III study (ClinicalTrials.gov, NCT03789292) randomized (1:1) subjects with active RA at 52 centers to receive CT-P17 or EU-adalimumab 40 mg subcutaneously every 2 weeks until week 52. Results to week 24 are reported here. The primary endpoint was 20% improvement by American College of Rheumatology criteria (ACR20) response rate at week 24. Equivalence was concluded if the corresponding confidence intervals (CIs) for the estimate of treatment difference were within predefined equivalence margins: – 15 to 15% (95% CI; European Medicines Agency assumption); – 12 to 15% (90% CI; Food and Drug Administration assumption). Additional efficacy, pharmacokinetic, usability, safety, and immunogenicity endpoints were evaluated.
Results: 648 subjects were randomized (324 CT-P17; 324 EU-adalimumab). The ACR20 response rate at week 24 was 82.7% (n = 268/324) in both groups (intention-to-treat population). The 95% CI (– 5.94 to 5.94) and 90% CI (– 4.98 to 4.98) were within predefined equivalence margins for both assumptions and equivalent efficacy was concluded. Additional endpoints and overall safety were comparable between groups. Mean trough serum concentrations of CT-P17 were slightly higher than those of EU-adalimumab. Immunogenicity was slightly lower numerically for the CT-P17 group than for the EU-adalimumab group.
Conclusions: CT-P17 and EU-adalimumab have equivalent efficacy and comparable safety and immunogenicity in subjects with active RA. Overall safety of CT-P17 is consistent with the known safety profile of reference adalimumab.
Stepping Forward to the Next Level: Totality of Evidence for the First High-Concentration Adalimumab Biosimilar, CT-P17
CT-P17 ist das erste hochkonzentrierte, citratfreie Adalimumab-Biosimilar, das nach umfassenden Studien in Europa zugelassen wurde. Die Sicherheit und Immunogenität des Original-Präparates Adalimumab sowie des mittels Selbstinjektion verabreichten CT-P17 waren in allen Studien ver...
Stepping Forward to the Next Level: Totality of Evidence for the First High-Concentration Adalimumab Biosimilar, CT-P17
Stepping Forward to the Next Level: Totality of Evidence for the First High-Concentration Adalimumab Biosimilar, CT-P17
Viapiana O et al.
Clin Drug Investig. 2022; 42(2):103-112
Abstract
Biosimilar regulatory evaluation considers the totality of evidence gathered through analytical, non-clinical and clinical studies. CT-P17 is the first high-concentration (100 mg/mL), citrate-free adalimumab biosimilar to receive regulatory approval in Europe for all indications held by reference adalimumab, following comprehensive non-clinical and clinical development programmes. State-of-the art physicochemical and biological methods demonstrated quality, analytical and functional comparability between CT-P17 and reference adalimumab; non-clinical in vivo studies supported biosimilarity. Three phase I and two phase III studies were conducted, with pharmacokinetic equivalence of CT-P17 and reference adalimumab shown in healthy volunteers, and equivalent efficacy demonstrated in patients with rheumatoid arthritis. Safety and immunogenicity profiles were comparable between CT-P17 and reference adalimumab across studies. CT-P17 is available for administration by autoinjector/prefilled pen (AI/PFP), prefilled syringe (PFS) and PFS with needle guard, providing diverse self-injection options for patients. Equivalent pharmacokinetics and comparable overall safety and usability were demonstrated between AI/PFP and PFS devices during the clinical development programme. All CT-P17 devices include fine, 29-gauge needles; combined with the citrate-free, high-concentration formulation, these characteristics reflect the newer reference adalimumab formulation (100 mg/mL) and are associated with reduced injection-site pain. The high-concentration formulation also facilitates treatment delivery via fewer injections. Compared with reference adalimumab, CT-P17 remains stable for longer at room temperature, enhancing ease of storage for patients and healthcare providers. In summary, the totality of evidence supports the biosimilarity of CT-P17 to high-concentration reference adalimumab, and several distinctive features differentiate it from existing adalimumab biosimilars.
Investigation of the Physicochemical and Biological Stability of the Adalimumab Biosimilar CT-P17
Analyse der Stabilität des Adalimumab-Biosimilars CT-P17 Vergleich zwischen CT-P17 und dem Referenz-Adalimumab sowie weiteren zugelassenen Biosimilars CT-P17 kann ohne signifikanten Verlust der Proteinstabilität verwendet werden, wenn es für 28 Tage bei 5 °C oder 25 °C und 60 % relativer Luftfeuchtigke...
Investigation of the Physicochemical and Biological Stability of the Adalimumab Biosimilar CT-P17
Investigation of the Physicochemical and Biological Stability of the Adalimumab Biosimilar CT-P17
Shin YK et al.
Adv. Therapy. 2021;38(11):5609-5622
Abstract
Introduction: CT-P17 (Celltrion, Inc., Incheon, Republic of Korea) is a biosimilar of reference adalimumab (Humira®; AbbVie Inc., North Chicago, IL, USA), which has recently received regulatory approval from the European Medicines Agency.
Methods: This analysis was designed to evaluate the stability profile of CT-P17 compared with reference adalimumab and the currently licensed adalimumab biosimilars ABP 501 (Amjevita®/Amgevita®; Amgen Inc., Thousand Oaks, CA, USA) and SB5 (Imraldi®; Biogen Inc., Cambridge, MA, USA) when stored at low temperature (5 °C) or room temperature (25 °C) with 60% relative humidity for up to 28 days.
Results: Multiple orthogonal and complementary tests demonstrated that CT-P17 was stable for 28 days under all tested conditions, as well as for protein concentrations tested (50 vs 100 mg/mL), type of delivery device (autoinjector vs prefilled syringe), and manufacturing date (recently manufactured vs aged for 17 months). There were slight differences among products in terms of charge variants, oxidation level, purity, and number of subvisible particles; however, overall, the quality of each product was maintained over 28 days.
Conclusion: Our data suggest that CT-P17 may be used without any significant loss of stability when stored at 5 °C or 25 °C with 60% relative humidity for up to 28 days, and was not impacted by protein concentration tested and delivery device. Comparative stability data suggest that the appropriate maximum storage period for CT-P17 may be up to 28 days at room temperature with 60% relative humidity.
An update on the adalimumab biosimilar landscape following the approval of the first high-concentration biosimilar, CTP17
Acht Adalimumab-Biosimilars haben bislang die Zulassung von der EMA und/oder der US-FDA erhalten. Diese können die Kosten im Gesundheitswesen senken und die Therapiemöglichkeiten für Patienten erweitern. CT-P17 ist unter den 8 zugelassenen das einzige Adalimumab-Biosimilar, das ...
An update on the adalimumab biosimilar landscape following the approval of the first high-concentration biosimilar, CTP17
An update on the adalimumab biosimilar landscape following the approval of the first high-concentration biosimilar, CTP17
Fusaro E et al.
Immunotherapy. 2021;14(3)
Abstract
Biosimilars can reduce healthcare costs and expand patient access to biologic therapies. Currently, eight adalimumab biosimilars have received regulatory approval from the EMA and/or the US FDA. Following recent EMA approval of the first high-concentration adalimumab biosimilar, CT-P17, this review provides a contemporary update on adalimumab biosimilars currently licensed in Europe and the USA. The totality of evidence from each clinical development program is summarized, and characteristics of each formulation and/or device that potentially affect the convenience of treatment for patients are discussed. Future perspectives are considered, including the potential impact of the FDA's first interchangeability designation for an adalimumab biosimilar, ahead of their entry into the US marketplace in 2023.
Efficacy and safety of switching from rituximab to biosimilar CT-P10 in rheumatoid arthritis: 72-week data from a randomized Phase 3 trial
Globale Phase-III-Studie zu Rituximab-Biosimilar bei rheumatoider Arthritis, 72-Wochen-Daten Vergleich zu zwei Rituximab-Originatoren (US-amerikanisch und EU) Nach Umstellung von den US-amerikanischen und EU-Rituximuab-Originatoren auf CT-P10 in der Behandlung v...
Efficacy and safety of switching from rituximab to biosimilar CT-P10 in rheumatoid arthritis: 72-week data from a randomized Phase 3 trial
Efficacy and safety of switching from rituximab to biosimilar CT-P10 in rheumatoid arthritis: 72-week data from a randomized Phase 3 trial
Shim SC et al.
Rheumatology (Oxford). 2019 1;58(12):2193-2202
Abstract
Objective: To evaluate the efficacy and safety of CT-P10, a rituximab biosimilar after a single switch, during a multinational, randomized, double-blind Phase 3 trial involving patients with RA.
Methods: Patients received 48 weeks’ treatment with CT-P10 or United States- or European Union-sourced reference rituximab (US-RTX and EU-RTX, respectively). Patients entering the extension period (weeks 48–72) remained on CT-P10 (CT-P10/CT-P10; n = 122) or US-RTX (US-RTX/US-RTX; n = 64), or switched to CT-P10 from US-RTX (US-RTX/CT-P10; n = 62) or EU-RTX (EU-RTX/CT-P10; n = 47) for an additional course. Efficacy endpoints included Disease Activity Score using 28 joints (DAS28), American College of Rheumatology (ACR) response rates, and quality of life-related parameters. Pharmacodynamics, immunogenicity and safety were also assessed.
Results: At week 72, similar improvements were observed by disease activity parameters including DAS28 and ACR response rate in the four extension period treatment groups. Quality of life improvements at week 72 vs baseline were similarly shown during the extension period in all groups. Newly developed anti-drug antibodies were detected in two patients following study drug infusion in the extension period. Similar pharmacodynamic and safety profiles were observed across groups.
Conclusion: Long-term use of CT-P10 up to 72 weeks was effective and well tolerated. Furthermore, switching from reference rituximab to CT-P10 in RA was well tolerated and did not result in any clinically meaningful differences in terms of efficacy, pharmacodynamics, immunogenicity and safety.
Long-Term Efficacy and Safety of Biosimilar CT-P10 Versus Innovator Rituximab in Rheumatoid Arthritis: 48-Week Results from a Randomized Phase III Trial
Globale Phase-III-Studie zu Rituximab-Biosimilar bei rheumatoider Arthritis, 48-Wochen-Daten Vergleich zu zwei Rituximab-Originatoren (US-amerikanisch und EU) CT-P10 weist in der Langzeitbehandlung von rheumatoider Arthritis eine zu den US-amerikan...
Long-Term Efficacy and Safety of Biosimilar CT-P10 Versus Innovator Rituximab in Rheumatoid Arthritis: 48-Week Results from a Randomized Phase III Trial
Long-Term Efficacy and Safety of Biosimilar CT-P10 Versus Innovator Rituximab in Rheumatoid Arthritis: 48-Week Results from a Randomized Phase III Trial
Suh CH et al.
BioDrugs. 2019;33(1):79-91
Abstract
Objective: The aim of this study was to investigate long-term clinical outcomes of extended treatment with CT-P10, a rituximab biosimilar, compared with rituximab reference products sourced from the USA and the EU (US-RTX and EU-RTX) in
rheumatoid arthritis (RA) for up to 48 weeks.
Methods: In this multinational, randomized, double-blind trial, adults with active RA received up to two courses of CT-P10, US-RTX, or EU-RTX alongside methotrexate. Efficacy endpoints included Disease Activity Score 28-joint count (DAS28) and American College of Rheumatology (ACR) response rates. Pharmacokinetics, pharmacodynamics, immunogenicity, and safety were also assessed.
Results: Of 372 patients randomized to the study drug, 330 (88.7%) completed the second treatment course. Mean change from baseline to week 48 in DAS28-C-reactive protein was comparable in the CT-P10 and combined rituximab (US-RTX
and EU-RTX) groups (− 2.7 and − 2.6, respectively). ACR20, ACR50, and ACR70 response rates at week 48 indicated no differences between groups (80.6%, 55.4%, and 31.7% vs. 79.8%, 53.9%, and 33.7% in the CT-P10 and combined rituximab groups, respectively). Similar improvements in the Health Assessment Questionnaire Disability Index and all medical outcomes in the Short Form 36-Item Health Survey, including physical and mental health, were seen in all groups. At week
48, antidrug antibodies were detected in 4.9%, 9.4%, and 8.6% of patients in the CT-P10, US-RTX, and EU-RTX groups, respectively. CT-P10 and rituximab displayed similar pharmacokinetic, pharmacodynamic, and safety profiles.
Conclusion: CT-P10 was similar to EU-RTX and US-RTX in terms of efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, and safety up to week 48.
Comparison of biosimilar CT-P10 and innovator rituximab in patients with rheumatoid arthritis: a randomized controlled Phase 3 trial
Globale Phase-III-Studie zu Rituximab-Biosimilar bei rheumatoider Arthritis, 24-Wochen-Daten Vergleich zu zwei Rituximab-Originatoren (US und EU) CT-P10 weist eine zu den US-amerikanischen und EU-Rituximuab-Originatoren vergleichbare Wirksamkeit, Pharmakokinetik, Immu...
Comparison of biosimilar CT-P10 and innovator rituximab in patients with rheumatoid arthritis: a randomized controlled Phase 3 trial
Comparison of biosimilar CT-P10 and innovator rituximab in patients with rheumatoid arthritis: a randomized controlled Phase 3 trial
Park W et al.
MAbs. 2018;10(6):934-943
Abstract
This multinational, randomized, double-blind trial, (ClinicalTrials.gov identifier NCT02149121) was designed to demonstrate equivalence in pharmacokinetics and efficacy between CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA). Adults with active RA were treated with CT-P10, United States-sourced RTX (US-RTX; Rituxan®), or European Union-sourced RTX (EU-RTX; MabThera®) at weeks 0 and 2. The co-primary pharmacokinetic endpoints were area under the serum concentration–time curve (AUC) from time zero to last measurable concentration (AUC0–last), AUC from time zero to infinity (AUC0–∞), and maximum concentration (Cmax) after two infusions. The primary efficacy endpoint was change from baseline to week 24 in Disease Activity Score using 28 joints-C-reactive protein (DAS28-CRP). Pharmacodynamics, immunogenicity, and safety were also assessed. 372 patients were randomly assigned to CT-P10 (n = 161) or RTX (n = 211 [US-RTX, n = 151; EU-RTX, n = 60]). For the co-primary pharmacokinetic endpoints, 90% confidence intervals (CI) for ratios of geometric means (CT-P10/US-RTX, CT-P10/EU-RTX or EU-RTX/US-RTX) all fell within the equivalence margin of 80–125%. Adjusted least squares (LS) mean (standard error) change from baseline in DAS28-CRP at week 24 was −2.13 (0.175) for CT-P10 and −2.09 (0.176) for RTX. The 95% CI (−0.29, 0.21) of the estimated treatment difference between CT-P10 and RTX (−0.04) was entirely within the efficacy equivalence margin of ±0.5. Pharmacodynamics, immunogenicity, and safety profiles were similar for CT-P10 and RTX. The pharmacokinetics of CT-P10, US-RTX, and EU-RTX were equivalent. CT-P10 and RTX were also equivalent in terms of efficacy and displayed similar pharmacodynamic, immunogenicity, and safety profiles up to week 24.
A pharmacokinetic evaluation of the rituximab biosimilar CT-P10 in the treatment of rheumatoid arthritis
Metaanalyse zu Rituximab-Biosimilar bei rheumatoider Arthritis Vergleich zu zwei Rituximab-Originatoren (US-amerikanisch und EU) Der Einsatz von CT-P10 hat in der Therapie von rheumatoider Arthritis das Potenzial zu einer wertvollen Alternative zum Rituximab-Originator.
A pharmacokinetic evaluation of the rituximab biosimilar CT-P10 in the treatment of rheumatoid arthritis
A pharmacokinetic evaluation of the rituximab biosimilar CT-P10 in the treatment of rheumatoid arthritis
Yoo DH et al.
Expert Opin Drug Metab Toxicol. 2020;16(12):1125-1132
Abstract
Introduction: CT-P10 is the first biosimilar of rituximab (RTX) for the treatment of rheumatoid arthritis (RA). The application of valuable biosimilar for the treatment of RA may decrease economic burden of society, and disease activity of RA. Thus, it is worthwhile to identify the economic advantage and further requirement for the proper use of CT-P10 in real world.
Areas covered: Literature searching was performed to identify suitable references written in English for this review article. Rituximab, biosimilar, CT-P10, and rheumatoid arthritis were used as keywords. Current state of RA treatment, position of RTX in the recommendations for the treatment of RA, current status of RTX biosimilar development were assessed before evaluating CT-P10 itself. Physicochemical property, pharmacokinetic profile through phase I to phase III studies, pharmacodynamics, toxicology data, clinical efficacy, and safety were reviewed
Expert opinion: As the first biosimilar to originator RTX, CT-P10 may be a useful alternative for the treatment of RA in all indications for originator RTX. In addition, more studies are required to identify long-term effectiveness and safety of CT-P10 in real world. It is also important to find out new indications of CT-P10 and effective mechanisms to lessen nocebo effect against biosimilar including CT-P10.
CT-P10 (Truxima™): A Rituximab Biosimilar
Metaanalyse zu Rituximab-Biosimilar in den Indikationen follikuläres Lymphom und rheumatoide Arthritis Vergleich zu zwei Rituximab-Originatoren (US-amerikanisch und EU) CT-P10 ist ein Rituximab-Biosimilar mit vergleichbaren Ergebnissen für Wirksamkeit, Verträglichkeit, Sicherheit und mit vergleichbaren physikalisch-chemischen und biologischen Eigenschaften.
CT-P10 (Truxima™): A Rituximab Biosimilar
CT-P10 (Truxima™): A Rituximab Biosimilar
Deeks ED
BioDrugs. 2017;31(3):275-278
Abstract
CT-P10 (Truxima™) is the first biosimilar of the reference monoclonal anti-CD20 antibody rituximab. It is approved for use in all indications for which reference rituximab is approved, including follicular lymphoma (FL), diffuse large B-cell non-Hodgkin’s lymphoma, chronic lymphocytic leukaemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis and microscopic polyangiitis. CT-P10 has similar physicochemical and pharmacodynamic properties to those of reference rituximab, and the pharmacokinetic biosimilarity of the agents has been shown in patients with RA or FL. CT-P10 demonstrated clinical efficacy equivalent to that of reference rituximab in patients with RA, and was generally well tolerated in this population as well as in patients with FL. The tolerability, immunogenicity and safety profiles of CT-P10 were similar to those of reference rituximab, and switching from reference rituximab to CT-P10 had no impact on safety or efficacy. The role of reference rituximab in the management of autoimmune conditions and cancers is well established and CT-P10 provides an effective biosimilar alternative for patients requiring rituximab therapy.
Unternehmensporträt: Infliximab-Biosimilar mit Zukunftspotenzial
Biosimilars erweitern als kostengünstige Alternative zum Originator die Behandlungsoptionen und ermöglichen eine zielgerichtete Therapie der unterschiedlichsten Krankheitsbilder, darunter Autoimmunerkrankungen und onkologische Erkrankungen. Das Infliximab-Biosimilar CT-P13 erhielt 2013 die Zulassung in der Europäischen Union (EU) im B...
Unternehmensporträt: Infliximab-Biosimilar mit Zukunftspotenzial
Unternehmensporträt: Infliximab-Biosimilar mit Zukunftspotenzial
Pickl S.
Beilage in GASTRONEWS 5/23 u. a.
Evolution der Biologikatherapie: vom Biosimilar zum Biobetter
Trotz aller Fortschritte in der Therapie der rheumatoiden Arthritis ist die Erkrankung längst nicht bei allen Patienten unter Kontrolle. Da die Entwicklung gänzlich neuer Biologika aufwendig sowie zeit- und kostenintensiv ist, könnte es sinnvoller sein, bewährte Substanzen so zu modifizieren, dass sie gegenüber den Originatorbiologika ei...
Evolution der Biologikatherapie: vom Biosimilar zum Biobetter
Evolution der Biologikatherapie: vom Biosimilar zum Biobetter
N.N.
BLICKPUNKT MEDIZIN zur Zeitschrift Aktuelle Rheumatologie 2022
Austausch von Biosimilars in der Apotheke
Aktuell ist der Gemeinsame Bundesausschuss (G-BA) dabei, die Austauschbarkeit von biologischen Arzneimitteln auf Apothekenebene zu regeln. Erklärtes Ziel ist ein höherer Anteil von Biosimilars bei der Verordnung biologischer Arzneimittel analog zu den Generika. Vertreter*innen der rheumatologischen Ärzteschaft, Krankenkassen sowie Betroffene diskutierten, o...
Austausch von Biosimilars in der Apotheke
Austausch von Biosimilars in der Apotheke
Sankawa Y.
Zeitschrift für Rheumatologie 81(5) 2022
TNF-α-Antikörper – Neues Adalimumab-Biosimilar zur Unterstützung der Therapieadhärenz
Seit Juni 2021 steht mit CT-P17 ein neues Adalimumab-Biosimilar auf dem deutschen Markt zur Verfügung. Zum Pflichttext Weiterlesen
TNF-α-Antikörper – Neues Adalimumab-Biosimilar zur Unterstützung der Therapieadhärenz
TNF-α-Antikörper – Neues Adalimumab-Biosimilar zur Unterstützung der Therapieadhärenz
Saber-Hamischagi S.
Kompendium Rheumatologie 14+15/2021
"Die subkutane Therapieoption wird den Stellenwert von Infliximab wieder erhöhen"
Infliximab, seinerzeit der erste zugelassene Tumornekrosefaktor-alpha (TNFα)-Blocker, hat die Therapiemöglichkeiten der Rheumatologen vor rund 20 Jahren revolutioniert. Die seit einem Jahr verfügbare erste subkutane (s. c.) Darreichungsform von Infliximab verhilft dem Klassiker jetzt zu einer Renaissance. Die häuslich...
"Die subkutane Therapieoption wird den Stellenwert von Infliximab wieder erhöhen"
"Die subkutane Therapieoption wird den Stellenwert von Infliximab wieder erhöhen"
Fath R.
Zeitschrift für Rheumatologie 80(7) 2021
Weniger Volumen für die Applikation – weniger Schmerzen bei der Injektion
Der TNF-alpha-Inhibitor Adalimumab zur Therapie chronisch-entzündlicher Erkrankungen wird vom Patienten subkutan appliziert, per Fertigpen oder Fertigspritze. Schmerzen bei der Injektion können die Adhärenz und damit den Therapieerfolg beeinträchtigen. Zum Pflichttext Weiterlesen
Weniger Volumen für die Applikation – weniger Schmerzen bei der Injektion
Weniger Volumen für die Applikation – weniger Schmerzen bei der Injektion
Fessler B.
Medical Tribune Sonderausgabe 3/2021: Rheumatologie · Schmerz
Hochdosiertes Adalimumab-Biosimilar Yuflyma® mit längerer Haltbarkeit bietet mehr Flexibilität
Bei der Behandlung einer Vielzahl chronisch-entzündlicher Erkrankungen hat sich das Adalimumab-Biosimilar Yuflyma ® bereits bewährt, darunter auch bei chronisch-entzündlichen Darmerkrankungen (CED) wie Morbus Crohn und Colitis ulcerosa. Es ist dem Originator hinsichtlich Wirksamkeit und Sicherheit äquival...
Hochdosiertes Adalimumab-Biosimilar Yuflyma® mit längerer Haltbarkeit bietet mehr Flexibilität
Hochdosiertes Adalimumab-Biosimilar Yuflyma® mit längerer Haltbarkeit bietet mehr Flexibilität
Pickl S.
Zeitschrift für Gastroenterologie 9/2023
Kann subkutanes Infliximab mehr?
Lässt sich die Infliximab-Therapie mithilfe der subkutanen Formulierung verbessern? Mit dieser Fragestellung setzte sich ein internationales Expertenteam auf der diesjährigen United European Gastroenterology Week (UEGW) in Wien auseinander. Seit Juli 2020 ist die subkutane (SC) Darreichungsform von Infliximab in der Europäischen Union für die Indikationen Morbus Cro...
Kann subkutanes Infliximab mehr?
Kann subkutanes Infliximab mehr?
Saber-Hamischagi S.
KOMPAKT Gastroenterologie 06/2022
Erstes hochkonzentriertes und citratfreies Adalimumab-Biosimilar: Konsequenzen für den Therapiealltag
Adalimumab ist ein vollständig humaner monoklonaler Antikörper, der ursprünglich als dritter Tumornekrosefaktor (TNF)-Antagonist eingeführt wurde und seither zur Biologika-basierten Revolutionierung der Behandlung immunvermittelter chronisch-entzündlicher Erkrankungen beigetragen hat. Mit dem Adali...
Erstes hochkonzentriertes und citratfreies Adalimumab-Biosimilar: Konsequenzen für den Therapiealltag
Erstes hochkonzentriertes und citratfreies Adalimumab-Biosimilar: Konsequenzen für den Therapiealltag
Sankawa Y.
Der Gastroenterologe 17(3) 2022
Chronisch-entzündliche Darmerkrankungen. Erweiterte Therapieoption der Anti-TNF-alpha-Therapie mit Infliximab s. c.
Infliximab ist seit langem eine zentrale Säule der CED-Behandlung. Da die Infusionstherapie jedoch mit regelmäßigem organisatorischen und zeitlichen Aufwand verbunden ist, war die Entwicklung der subkutanen Applikationsform von Infliximab ein großer Fortschritt. Zwei Fallbeispiele dok...
Chronisch-entzündliche Darmerkrankungen. Erweiterte Therapieoption der Anti-TNF-alpha-Therapie mit Infliximab s. c.
Chronisch-entzündliche Darmerkrankungen. Erweiterte Therapieoption der Anti-TNF-alpha-Therapie mit Infliximab s. c.
Zeißig S. et al.
CASE REPORT zur Zeitschrift für Gastroenterologie 2/2022
Infliximab-Biosimilar: unterschiedliche Applikation, vergleichbare Wirksamkeit
Zulassungsrelevante Daten zeigen, dass sich die Umstellung einer intravenösen auf eine subkutane Therapie mit CT-P13 nicht nachteilig auf das klinische Outcome von Patienten mit Morbus Crohn oder Colitis ulcerosa auswirkt. Post-hoc Analysen dieser Daten zeigten zudem, dass eine Monotherapie mit CT-P13 SC über 54 Wochen e...
Infliximab-Biosimilar: unterschiedliche Applikation, vergleichbare Wirksamkeit
Infliximab-Biosimilar: unterschiedliche Applikation, vergleichbare Wirksamkeit
Sankawa Y.
Der Internist 12/2021
CT-P13 SC in der Therapie chronisch entzündlicher Darmerkrankungen: Subkutane Darreichung von Infliximab überzeugt
Die subkutane Darreichungsform des Infliximab-Biosimilars CT-P13 weist bei Patienten mit chronisch-entzündlichen Darmerkrankungen eine vergleichbare anhaltende Wirksamkeit und Sicherheit auf wie die intravenöse Applikation. Zum Pflichttext Weiterlesen
CT-P13 SC in der Therapie chronisch entzündlicher Darmerkrankungen: Subkutane Darreichung von Infliximab überzeugt
CT-P13 SC in der Therapie chronisch entzündlicher Darmerkrankungen: Subkutane Darreichung von Infliximab überzeugt
Fischer G.
BLICKPUNKT MEDIZIN zur Zeitschrift für Gastroenterologie 8/2021
Intravenöse/subkutane Sequenztherapie – Hohe Akzeptanz von Infliximab zur subkutanen Injektion
Seit einem Jahr steht zur Behandlung von Menschen mit einer chronisch-entzündlichen Darmerkrankung (CED) neben der intravenösen auch eine subkutane Darreichungsform für Infliximab zur Verfügung. Zum Pflichttext Weiterlesen
Intravenöse/subkutane Sequenztherapie – Hohe Akzeptanz von Infliximab zur subkutanen Injektion
Intravenöse/subkutane Sequenztherapie – Hohe Akzeptanz von Infliximab zur subkutanen Injektion
Schreiber S.
Kompendium Gastroenterologie 24/2021
Adalimumab-Biosimilar bei Morbus Crohn und Colitis ulcerosa
In der Therapie chronisch-entzündlicher Darmerkrankungen, wie Morbus Crohn und Colitis ulcerosa, werden monoklonale Antikörper gegen den Tumornekrosefaktor α (TNF α) seit langem eingesetzt. Das neu zugelassene Adalimumab-Biosimilar CT-P17 weist eine vergleichbare Wirksamkeit und Sicherheit zum Original-Präparat bei gleichzeitig reduziertem...
Adalimumab-Biosimilar bei Morbus Crohn und Colitis ulcerosa
Adalimumab-Biosimilar bei Morbus Crohn und Colitis ulcerosa
Wepner U.
Der Gastroenterologie 4/2021
Subkutanes Infliximab – mehr Bioinnovation als Biosimilar
Mit der Entwicklung von CT-P13 SC steht in der Europäischen Union (EU) seit November 2019 erstmals eine subkutane Darreichungsform von Infliximab zur Therapie der Rheumatoiden Arthritis zur Verfügung. Im Juli 2020 erweiterte die Europäische Kommission die Zulassung um Morbus Crohn, Colitis ulcerosa und weitere Indikationen. Zwar erfolgte die...
Subkutanes Infliximab – mehr Bioinnovation als Biosimilar
Subkutanes Infliximab – mehr Bioinnovation als Biosimilar
N.N.
KOMPAKT Gastroenterologie 03/2021
Keine erhöhte Immunogenität bei subkutaner CED-Therapie mit Biologikum
Keine vermehrte Bildung von Anti-Drug-Antikörpern unter Therapie mit subkutanem Infliximab feststellbar. Subkutane und intravenöse Darreichungsformen zeigten ein vergleichbares Sicherheits- und Wirkungsprofil. Zum Pflichttext Weiterlesen
Keine erhöhte Immunogenität bei subkutaner CED-Therapie mit Biologikum
Keine erhöhte Immunogenität bei subkutaner CED-Therapie mit Biologikum
Wülker A.
Medical Tribune Gastroenterologie Hepatologie 3/2020
Psoriasis, Acne inversa, CED: Biologika bei chronisch-entzündlichen Erkrankungen: TNF-Biosimilars – steinalt und doch ganz neu
Für die wirksame Behandlung chronisch entzündlicher Erkrankungen wie Psoriasis, Psoriasis-Arthritis, Acne inversa oder chronisch entzündlicher Darmerkrankungen (CED) stehen heute Biosimilars der TNF (Tumornekrose) alpha-Inhibitoren Adalimumab oder Infliximab zur Verfügung. ...
Psoriasis, Acne inversa, CED: Biologika bei chronisch-entzündlichen Erkrankungen: TNF-Biosimilars – steinalt und doch ganz neu
Psoriasis, Acne inversa, CED: Biologika bei chronisch-entzündlichen Erkrankungen: TNF-Biosimilars – steinalt und doch ganz neu
Pickl S.
Aktuelle Dermatologie 8/9 2023
Efficacy and Safety of Candidate Biosimilar CT‑P43 Versus Originator Ustekinumab in Moderate to Severe Plaque Psoriasis: 28‑Week Results of a Randomised, Active‑Controlled, Double‑Blind, Phase III Study
Randomisierte, doppelblinde Phase-III-Studie zu Ustekinumab-Biosimilar bei moderater bis schwerer Psoriasis Vergleich zwischen Ustekinumab-Biosimilar und -Originator Datenauswertung nach 28 Wochen D...
Efficacy and Safety of Candidate Biosimilar CT‑P43 Versus Originator Ustekinumab in Moderate to Severe Plaque Psoriasis: 28‑Week Results of a Randomised, Active‑Controlled, Double‑Blind, Phase III Study
Efficacy and Safety of Candidate Biosimilar CT‑P43 Versus Originator Ustekinumab in Moderate to Severe Plaque Psoriasis: 28‑Week Results of a Randomised, Active‑Controlled, Double‑Blind, Phase III Study
Papp KA et al.
BioDrugs. 2024; 38:121–131
Abstract
Background
CT-P43 is a candidate ustekinumab biosimilar in clinical development.
Objectives
This paper aims to demonstrate equivalent efficacy of CT-P43 to originator ustekinumab in adults with moderate to severe plaque psoriasis.
Methods
This double-blind, phase III trial randomised patients (1:1) to receive subcutaneous CT-P43 or originator ustekinumab (45/90 mg for patients with baseline body weight ≤ 100 kg/> 100 kg) at week 0 and week 4 in Treatment Period I. Prior to week 16 dosing in Treatment Period II, patients receiving originator ustekinumab were re-randomised (1:1) to continue originator ustekinumab or switch to CT-P43; patients initially randomised to CT-P43 continued receiving CT-P43 (at weeks 16, 28 and 40). The primary endpoint of the trial was mean per cent improvement from baseline in Psoriasis Area Severity Index (PASI) score at week 12. Equivalence was concluded if confidence intervals (CIs) for the estimate of treatment difference were within pre-defined equivalence margins: ± 10% [90% CI; modified intent-to-treat set; Food and Drug Administration (FDA) approach] or ± 15% [95% CI; full analysis set for patients only receiving 45 mg doses in Treatment Period I; European Medicines Agency (EMA) approach]. Additional efficacy, pharmacokinetic, safety and immunogenicity endpoints were evaluated through week 52. Results to week 28 are reported here.
Results
In Treatment Period I, 509 patients were randomised (CT-P43: N = 256; originator ustekinumab: N = 253). The mean per cent improvement in PASI score at week12 was 77.93% and 75.89% for CT-P43 and originator ustekinumab, respectively (FDA approach); per the EMA approach, corresponding values were 78.26% and 77.33%. Estimated treatment differences were 2.05 (90% CI −0.23, 4.32) and 0.94 (95% CI −2.29, 4.16); equivalence was achieved for both sets of assumptions. Further efficacy parameters and pharmacokinetic, safety and immunogenicity outcomes were comparable between treatment groups, including after switching from originator ustekinumab to CT-P43.
Conclusions
CT-P43 demonstrated equivalent efficacy to originator ustekinumab in patients with moderate to severe plaque psoriasis, with comparable pharmacokinetic, safety and immunogenicity profiles.
Neues Biosimilar: therapeutisch gleichwertig, weniger immunogen
Ustekinumab dient zur Behandlung von chronisch-entzündlichen Erkrankungen wie Plaque-Psoriasis, Psoriasis-Arthritis, Morbus Crohn und Colitis ulcerosa. Basierend auf umfassender Evidenz hat die Europäische Kommission im August 2024 das neue Ustekinumab-Biosimilar SteQeyma® zugelassen*. Für dieses wurde in der Indikation mittelschwere b...
Neues Biosimilar: therapeutisch gleichwertig, weniger immunogen
Neues Biosimilar: therapeutisch gleichwertig, weniger immunogen
Dr. Hofmann-Aßmus
Hautnah Dermatologie 11/2024
Basierend auf einer umfassenden Evidenz hat die Europäische Kommission im August 2024 ein neues Ustekinumab-Biosimilar zugelassen, das voraussichtlich ab Herbst 2024 zur Verfügung stehen wird. Für die Indikation der mittelschweren bis schweren Plaque-Psoriasis belegt eine Phase-III-Studie eine vergleichbare Wirksamkeit gegenüber dem Originator, sowie einen numerischen Vorteil hinsichtlich der Immunogenität [1,2]. Das neue Ustekinumab-Biosimilar (CT-P43) lässt sich aufgrund entsprechender Äquivalenz-Nachweise bei verschiedenen chronisch-entzündlichen Erkrankungen als alternative Therapieoption verordnen.