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, Byong Duk; Pesegova, Marina; Alexeeva, Olga; Осипенко, М. Ф.; Lahat, Adi; Dorofeev, A. E.; Fishman, Sigal; Levchenko, Olena; Cheon, Jae Hee; Scribano, Maria Lia; Mateescu, Bogdan; Lee, Kang Moon; Eun, Chang Soo; Lee, Sang Joon; Lee, Sung Young; Kim, Ho Ung; Schreiber, Stefan; Fowler, Heather; Cheung, Raymond; Kim, Young Ho

doi:10.1016/s0140-6736(18)32196-2

Cited by 175 publications

(152 citation statements)

References 25 publications

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“…Additionally, the proportion of patients remaining on dual biologic therapy at 1 year was similar to the endoscopic response rate. Although there was no preliminary signal, adverse event rates were comparable to previous TNF‐antagonist data 25‐27 …”

Section: Discussionsupporting

confidence: 72%

Efficacy and safety of simultaneous treatment with two biologic medications in refractory Crohn’s disease

Yang

Panaccione

Whitmire

et al. 2020

Aliment Pharmacol Ther

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Background: Biologic therapies in patients with Crohn's disease often yield low clinical and endoscopic remission rates. After multiple failed therapies, combining two biologic therapies is possibly the sole medical alternative to recurrent surgery.However, data on this approach are limited. Aims:To assess the efficacy and safety of concomitant use of two biologic therapies in the largest cohort to date of refractory Crohn's disease patients. Methods: Data were extracted from Crohn's disease patients started on dual biologic therapy at two referral centres. Biologics utilised include infliximab, adalimumab, vedolizumab, ustekinumab, certolizumab and golimumab. The primary outcome was endoscopic improvement (>50% reduction in Simplified Endoscopic Score-Crohn's disease [SES-CD] or explicitly stated). Endoscopic remission (SES-CD < 3 or stated), clinical response (Crohn's disease-patient-reported outcome-2 score [PRO2] reduced by 8), clinical remission (PRO2 < 8), and C-reactive protein (CRP) were also assessed.Results: A total of 22 patients with 24 therapeutic trials of dual biologic therapy were identified. The majority of patients had prior surgical resections (91%), stricturing (59%) or penetrating (36%) phenotype, and perianal fistulas (50%). Median number of prior failed biologics was 4. Endoscopic improvement occurred in 43% of trials and 26% achieved endoscopic remission. Fifty per cent had clinical response and 41% achieved clinical remission. There were significant post-treatment reductions in median ] to 6.0 [2.5-8.0], P = 0.0005], to 13.4 [4.6-21.8], P = 0.002] and .0] to 9.0 [4.0-14.0], P = 0.02).Presence of perianal fistulas decreased from 50% to 33%. Adverse events occurred in 13% of trials. Conclusion:Dual biologic therapy was associated with clinical, biomarker and endoscopic improvements in selected patients with refractory Crohn's disease who failed multiple biologics. Further studies are needed to validate this approach.

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Section: Discussionsupporting

confidence: 72%

Efficacy and safety of simultaneous treatment with two biologic medications in refractory Crohn’s disease

Yang

Panaccione

Whitmire

et al. 2020

Aliment Pharmacol Ther

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“…Considering CT-P13 evaluation in IMIDs, multiple endpoints were evaluated during the PLANETRA equivalence study, including Disease Activity Score in 28 joints (DAS28), based on C-reactive protein (CRP), and American College of Rheumatology and European League Against Rheumatism (EULAR) response rates; the endpoints were highly similar between CT-P13 and reference infliximab at week 30 [33]. The postmarketing phase III PLANETCD study comparing CT-P13 and reference infliximab in patients with Crohn's disease (CD) used a Crohn's Disease Activity Index-based primary endpoint [34], whereas two cohort studies comparing these agents in patients with either CD or UC employed composite primary endpoints (comprising death, CD-related surgery, all-cause hospitalization, and reimbursement for other biologics) [35,36]. The sensitive endpoints of endoscopic remission/mucosal healing were also employed in the PLANETCD study as a tertiary efficacy endpoint [34] and have been assessed in prospective observational studies of CT-P13 treatment in patients with UC [37][38][39][40][41].…”

Section: Key Pointsmentioning

confidence: 99%

“…For extrapolation to be permitted, biosimilarity must have been demonstrated in in vitro, nonclinical, and clinical studies, and the rationale for extrapolation must be scientifically justifiable [3]. Today, approval of CT-P13 in IBD is also supported by real-world evidence and clinical trial data [34,[120][121][122][123], including from the randomized, double-blind, noninferiority phase IV NOR-SWITCH study [120] and a Hungarian prospective observational cohort study [124]. To our knowledge, no published clinical trials evaluating the approved adalimumab biosimilars ABP 501, BI 695501, or SB5 in IBD, or real-world evidence for other infliximab biosimilars exist.…”

Section: Gastroenterologists' Perspective: Earlier Introduction Of Bimentioning

confidence: 99%

The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases

Kim

Alten

Avedano³

et al. 2020

Drugs

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Biologics have transformed the treatment of immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Biosimilars-biologic medicines with no clinically meaningful differences in safety or efficacy from licensed originators-can stimulate market competition and have the potential to expand patient access to biologics within the parameters of treatment recommendations. However, maximizing the benefits of biosimilars requires cooperation between multiple stakeholders. Regulators and developers should collaborate to ensure biosimilars reach patients rapidly without compromising stringent quality, safety, or efficacy standards. Pharmacoeconomic evaluations and payer policies should be updated following biosimilar market entry, minimizing the risk of imposing nonmedical barriers to biologic treatment. In RA, disparities between treatment guidelines and national reimbursement criteria could be addressed to ensure more uniform patient access to biologics and enable rheumatologists to effectively implement treat-to-target strategies. In IBD, the cost-effectiveness of biologic treatment earlier in the disease course is likely to improve when biosimilars are incorporated into pharmacoeconomic analyses. Patient understanding of biosimilars is crucial for treatment success and avoiding nocebo effects. Full understanding of biosimilars by physicians and carefully considered communication strategies can help support patients initiating or switching to biosimilars. Developers must operate efficiently to be sustainable, without undermining product quality, the reliability of the supply chain, or pharmacovigilance. Developers should also facilitate information sharing to meet the needs of other stakeholders. Such collaboration will help to ensure a sustainable future for both the biosimilar market and healthcare systems, supporting the availability of effective treatments for patients.

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“…Recently, Ye et al 28 reported the results from a phase III randomized, double blind parallel group trial, conducted in patients with moderate to severe CD. These authors compared the efficacy of CT-P13 to originator infliximab, with 220 patients from 16 countries.…”

Section: Efficacy and Safety In Prospective Studiesmentioning

confidence: 99%

“…18,19 A phase III study comparing CT-P13 with originator infliximab in CD showed no difference in the rate of infusion reactions between both groups at week 30 (CT-P13 7.2% vs. originator infliximab 8.3%). 28 Bálint et al 39 focused on the immunogenicity of CT-P13 in a central European cohort, including 384 consecutive patients (253 CD and 131 UC; 291 Hungarian and 93 Czech) from 13 Hungarian and 1 Czech tertiary IBD sites. Mean CT-P13 trough levels (TLs) were 20.1, 14.7, and 5.0 μg/mL at weeks 2, 6, and 14, respectively, and cumulative rates of ADA positivity were 8.7%, 19.3%, and 28.0% at weeks 0, 14, and 30, respectively.…”

Section: Immunogenicity and Pharmacokineticsmentioning

confidence: 99%

Biosimilars: concept, current status, and future perspectives in inflammatory bowel diseases

Park

Lukáš

et al. 2020

Intest Res

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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

Cited by 175 publications

References 25 publications

Efficacy and safety of simultaneous treatment with two biologic medications in refractory Crohn’s disease

Efficacy and safety of simultaneous treatment with two biologic medications in refractory Crohn’s disease

The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases

Biosimilars: concept, current status, and future perspectives in inflammatory bowel diseases

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