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Clinical Trial
. 2019 Feb;33(1):79-91.
doi: 10.1007/s40259-018-00331-4.

Long-Term Efficacy and Safety of Biosimilar CT-P10 Versus Innovator Rituximab in Rheumatoid Arthritis: 48-Week Results from a Randomized Phase III Trial

Chang-Hee Suh  1 , Dae Hyun Yoo  2 , Alfredo Berrocal Kasay  3 , Elia Chalouhi El-Khouri  4 , Francisco Fidenci Cons Molina  5 , Pavel Shesternya  6 , Pedro Miranda  7 , Francisco G Medina-Rodriguez  8 , Piotr Wiland  9 , Slawomir Jeka  10 , Jose Chavez-Corrales  11 , Thomas Linde  12 , Pawel Hrycaj  13 , Mauricio Abello-Banfi  14 , Ihor Hospodarskyy  15 , Janusz Jaworski  16 , Mariusz Piotrowski  17 , Marek Brzosko  18 , Marek Krogulec  19 , Sergii Shevchuk  20 , Armando Calvo  21 , Daina Andersone  22 , Won Park  23 , Seung Cheol Shim  24 , Sang Joon Lee  25 , Sung Young Lee  25
Affiliations
Clinical 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

Chang-Hee Suh et al. BioDrugs. 2019 Feb.

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. CLINICALTRIALS.

Gov identifier: NCT02149121.

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Conflict of interest statement

Conflicts of interest

Chang-Hee Suh received consulting fees (< US$10,000) during the conduct of the study and grants outside the submitted work from CELLTRION, Inc. Dae Hyun Yoo is a scientific consultant (no fee), is on the speaker’s bureau of CELLTRION, Inc., and has received research grants not related to this clinical study. Pedro Miranda received fees from CELLTRION for conducting the trial and has performed trials for CELLTRION outside the submitted work. Won Park and Seung Cheol Shim have received consulting fees (< US$10,000) from CELLTRION, Inc. Sang Joon Lee and Sung Young Lee are employees of CELLTRION, Inc. Alfredo Berrocal Kasay, Elias Chalouhi El-Khouri, Francisco Fidencio Cons Molina, Pavel Shesternya, Francisco G. Medina-Rodriguez, Piotr Wiland, Slawomir Jeka, Jose Chavez-Corrales, Thomas Linde, Pawel Hrycaj, Mauricio Abello-Banfi, Ihor Hospodarskyy, Janusz Jaworski, Mariusz Piotrowski, Marek Brzosko, Marek Krogulec, Sergii Shevchuk, Armando Calvo, and Daina Andersone have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval and consent to participate

The study was performed in accordance with the Declaration of Helsinki [11] and Good Clinical Practice guidelines [12]. The study protocol was reviewed and approved by the relevant independent ethics committee at each site, and all patients provided written informed consent.

Figures

Fig. 1
Fig. 1
Patient disposition. * indicates two patients in the CT-P10 group were discontinued as both had not previously received tumor necrosis factor-antagonist treatment (major protocol deviation). ** indicates three patients discontinued after week 24 (one from the CT-P10 group due to withdrawal of patient consent, and two from the US-RTX group—one due to lack of efficacy and one due to signs of disease progression). *** indicates four patients (two each from the CT-P10 and US-RTX groups) did not satisfy the retreatment criteria after the first treatment course and were monitored up to week 48. RTX rituximab
Fig. 2
Fig. 2
Efficacy of CT-P10 and combined rituximab over 48 weeks (efficacy population)a: a mean change from baseline in DAS28-ESR; b DAS28-CRP; c proportion of patients achieving ACR20, ACR50, and ACR70 criteria; and d mean hybrid ACR score. aData after week 24 are from the efficacy population–2nd treatment course subset. ACR American College of Rheumatology, CRP C-reactive protein, DAS28 Disease Activity Score 28-Joint Count, ESR erythrocyte sedimentation rate, RTX rituximab, SD standard deviation, SE standard error
Fig. 3
Fig. 3
Effects of CT-P10 and combined rituximab on patient-reported outcomes (efficacy population)a: a HAQ-DI over 48 weeks and b SF-36 at week 48. aData after week 24 are from the efficacy population–2nd treatment course subset. HAQ-DI Health Assessment Questionnaire Disability Index, RTX rituximab, SD standard deviation, SF-36 Short Form 36-Item Health Survey
See this image and copyright information in PMC

References

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