Efficacy and safety of switching from rituximab to biosimilar CT-P10 in rheumatoid arthritis: 72-week data from a randomized Phase 3 trial

Seung Cheol Shim, Ljubinka Božić-Majstorović, Alfredo Berrocal Kasay, Elias Chalouhi El-Khouri, Fedra Irazoque-Palazuelos, Francisco Fidencio Cons Molina, Francisco G Medina-Rodriguez, Pedro Miranda, Pavel Shesternya, Jose Chavez-Corrales, Piotr Wiland, Slawomir Jeka, Olena Garmish, Pawel Hrycaj, Natalia Fomina, Won Park, Chang-Hee Suh, Sang Joon Lee, Sung Young Lee, Yun Ju Bae, Dae Hyun Yoo, Seung Cheol Shim, Ljubinka Božić-Majstorović, Alfredo Berrocal Kasay, Elias Chalouhi El-Khouri, Fedra Irazoque-Palazuelos, Francisco Fidencio Cons Molina, Francisco G Medina-Rodriguez, Pedro Miranda, Pavel Shesternya, Jose Chavez-Corrales, Piotr Wiland, Slawomir Jeka, Olena Garmish, Pawel Hrycaj, Natalia Fomina, Won Park, Chang-Hee Suh, Sang Joon Lee, Sung Young Lee, Yun Ju Bae, Dae Hyun Yoo

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.

Trail registration: ClinicalTrials.gov, https://ichgcp.net/clinical-trials-registry/NCT02149121" title="See in ClinicalTrials.gov">NCT02149121.

Keywords: B cells; CT-P10; DMARDs (biologic); anti-TNF; biosimilar; disease activity; rheumatoid arthritis; rituximab; switch.

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig . 1
Fig. 1
Patient flow Reasons for drop-out in the main period have been published previously [18]. aIncludes one patient who did not receive the second treatment course (due to not satisfying safety criteria) and was monitored up to week 48. bRandomization in the extension period was stratified by the number of courses received in the main period and EULAR-CRP response status (responder vs non-responder) assessed at week 40. cThree patients were discontinued due to consent withdrawal (one in CT-P10/CT-P10, two in US-RTX/CT-P10). EU: European Union; RTX: rituximab; US: United States.
Fig . 2
Fig. 2
Efficacy outcomes (A) Mean DAS28-CRP. (B) Mean DAS28-ESR. (C) Proportion of patients achieving clinical response according to ACR20, ACR50 and ACR70 criteria. (D) Mean hybrid ACR score. (E) Proportion of patients with good/moderate EULAR-CRP. Values for all data points in (A–D) are provided in Supplementary Tables S5–S8, available at Rheumatology online. Data are shown for the efficacy population [17] (including the second treatment course subset [18]) and the extension period subset beyond weeks 24 and 48, respectively. DAS28: Disease Activity Score using 28 joints; EU: European Union; RTX: rituximab; US: United States.

References

    1. Bugatti S, Vitolo B, Caporali R, Montecucco C, Manzo A.. B cells in rheumatoid arthritis: from pathogenic players to disease biomarkers. Biomed Res Int 2014;2014:1.
    1. Marston B, Palanichamy A, Anolik JH.. B cells in the pathogenesis and treatment of rheumatoid arthritis. Curr Opin Rheumatol 2010;22:307–15.
    1. Boross P, Leusen JH.. Mechanisms of action of CD20 antibodies. Am J Cancer Res 2012;2:676–90.
    1. Edwards JC, Szczepanski L, Szechinski J.. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004;350:2572–81.
    1. Cohen SB, Emery P, Greenwald MW. et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 2006;54:2793–806.
    1. Emery P, Fleischmann R, Filipowicz-Sosnowska A. et al. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum 2006;54:1390–400.
    1. European Medicines Agency. MabThera Summary of Product Characteristics; 2018. (14 May 2019, date last accessed).
    1. Genentech Inc. Rituxan Prescribing Information; 2018. (14 May 2019, date last accessed).
    1. Generics and Biosimilars Initiative. EC approval for first cancer biosimilar Truxima; 2017. (14 May 2019, date last accessed).
    1. European Medicines Agency. Truxima Summary of Product Characteristics; 2018. (14 May 2019, date last accessed).
    1. European Medicines Agency. Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues; 2014. (14 May 2019, date last accessed).
    1. U.S. Food and Drug Administration. Scientific considerations in demonstrating biosimilarity to a reference product: Guidance for industry; 2015. (14 May 2019, date last accessed).
    1. Buske C, Ogura M, Kwon HC, Yoon SW.. An introduction to biosimilar cancer therapeutics: definitions, rationale for development and regulatory requirements. Future Oncol 2017;13:5–16.
    1. Yoo DH, Suh CH, Shim SC. et al. A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis. Ann Rheum Dis 2017;76:566–70.
    1. Kim WS, Buske C, Ogura M. et al. Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 compared with rituximab in patients with previously untreated advanced-stage follicular lymphoma: a randomised, double-blind, parallel-group, non-inferiority phase 3 trial. Lancet Haematol 2017;4:e362–73.
    1. Ogura M, Sancho JM, Cho SG. et al. Efficacy, pharmacokinetics and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low tumour burden follicular lymphoma: a randomised, double-blind, parallel-group phase 3 trial. Lancet Haematol 2018;5:e543–53.
    1. Park W, Božić-Majstorović L, Milakovic D. et al. Comparison of biosimilar CT-P10 and innovator rituximab in patients with rheumatoid arthritis: a randomised controlled Phase III trial. MAbs 2018;10:934–43.
    1. Suh C-H, Yoo DH, Berrocal Kasay A. et al. Long-term efficacy and safety of biosimilar CT-P10 versus innovator rituximab in rheumatoid arthritis: 48-week results from a randomized phase III trial. BioDrugs 2019;33:79–91.
    1. World Medical Association. WMA Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects; 2018. (14 May 2019, date last accessed).
    1. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. International Conference on Harmonisation Tripartite Guideline. Guidance for Good Clinical Practice E6(R1); 1996. (14 May 2019, date last accessed).
    1. van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol 2000;27:261–3.
    1. Yoo DH, Suh CH, Shim SC. et al. Efficacy, safety and pharmacokinetics of up to two courses of the rituximab biosimilar CT-P10 versus innovator rituximab in patients with rheumatoid arthritis: results up to week 72 of a phase I randomized controlled trial. BioDrugs 2017;31:357–67.
    1. Park W, Suh CH, Shim SC. et al. Efficacy and safety of switching from innovator rituximab to biosimilar CT-P10 compared with continued treatment with CT-P10: results of a 56-week open-label study in patients with rheumatoid arthritis. BioDrugs 2017;31:369–77.
    1. Keystone EC, Cohen SB, Emery P. et al. Multiple courses of rituximab produce sustained clinical and radiographic efficacy and safety in patients with rheumatoid arthritis and an inadequate response to 1 or more tumor necrosis factor inhibitors: 5-year data from the REFLEX study. J Rheumatol 2012;39:2238–46.
    1. van Vollenhoven RF, Emery P, Bingham CO. et al. Long-term safety of rituximab in rheumatoid arthritis: 9.5-year follow-up of the global clinical trial programme with a focus on adverse events of interest in RA patients. Ann Rheum Dis 2013;72:1496–502.
    1. Williams JH, Hutmacher MM, Zierhut ML. et al. Comparative assessment of clinical response in patients with rheumatoid arthritis between PF-05280586, a proposed rituximab biosimilar, and rituximab. Br J Clin Pharmacol 2016;82:1568–79.
    1. Smolen JS, Cohen SB, Tony HP. et al. A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis. Ann Rheum Dis 2017;76:1598–602.
    1. Jurczak W, Moreira I, Kanakasetty GB. et al. Rituximab biosimilar and reference rituximab in patients with previously untreated advanced follicular lymphoma (ASSIST-FL): primary results from a confirmatory phase 3, double-blind, randomised, controlled study. Lancet Haematol 2017;4:e350–e61.
    1. Cohen SB, Burgos-Vargas R, Emery P. et al. An extension study of PF-05280586, a potential rituximab biosimilar, versus rituximab in subjects with active rheumatoid arthritis. Arthritis Care Res (Hoboken) 2018;70:1598–606.
    1. Cohen S, Emery P, Greenwald M. et al. A phase I pharmacokinetics trial comparing PF-05280586 (a potential biosimilar) and rituximab in patients with active rheumatoid arthritis. Br J Clin Pharmacol 2016;82:129–38.
    1. Singh JA, Saag KG, Bridges SL Jr. et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2016;68:1–25.
    1. Putrik P, Ramiro S, Kvien TK. et al. Inequities in access to biologic and synthetic DMARDs across 46 European countries. Ann Rheum Dis 2014;73:198–206.
    1. Smolen JS, Landewé R, Bijlsma J. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960–77.
    1. Kay J, Schoels MM, Dörner T. et al. Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases. Ann Rheum Dis 2018;77:165–74.
    1. Glintborg B, Sørensen IJ, Loft AG. et al. A nationwide non-medical switch from originator infliximab to biosimilar CT-P13 in 802 patients with inflammatory arthritis: 1-year clinical outcomes from the DANBIO registry. Ann Rheum Dis 2017;76:1426–31.
    1. Jørgensen KK, Olsen IC, Goll GL. et al. 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. Lancet 2017;389:2304–16.
    1. Nikiphorou E, Kautiainen H, Hannonen P. et al. Clinical effectiveness of CT-P13 (infliximab biosimilar) used as a switch from Remicade (infliximab) in patients with established rheumatic disease. Report of clinical experience based on prospective observational data. Expert Opin Biol Ther 2015;15:1677–83.
    1. Vergara-Dangond C, Sáez Belló M, Climente Martí M, Llopis Salvia P, Alegre-Sancho JJ.. Effectiveness and safety of switching from innovator infliximab to biosimilar CT-P13 in inflammatory rheumatic diseases: a real-world case study. Drugs R D 2017;17:481–5.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner