Impact of Anti-Drug Antibody on Efficacy and Safety over Week 24 in Both CT-P10 and Innovator Rituximab Treatment Groups

Dae-Hyun Yoo¹, Won Park², Slawomir Jeka³, Fidencio Cons Molina⁴, Pawel Hrycaj⁵, Piotr Wiland⁶, Wolfgang Spieler⁷, Eun Young Lee⁸, Francisco G. Medina-Rodriguez⁹, Pavel Shesternya¹⁰, Sebastiao Radominski¹¹, Dong Hyuk Sheen¹², Mie Jin Lim¹³, Jung-Yoon Choe¹⁴, Leysan Myasoutova¹⁵, Taek Kwon¹⁶, Sang Joon Lee¹⁶, Seung-Cheol Shim¹⁷ and Chang-Hee Suh¹⁸, ¹Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, ²Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, Incheon, South Korea, ³University Hospital Nr 2 Dr. Jan Biziel, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Clinic of Rheumatology and Connective Tissue Diseases, Bydgoszcz, Poland, ⁴Centro de Investigacion en Artritis y Osteoporosis, Mexicali, Mexico, ⁵Department of Rheumatology and Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland, ⁶Department of Rheumatology, Medical University of Wroclaw, Wroclaw, Poland, ⁷Osteologie und Rheumatologie, ZeFOR GmbH Zentrum für Forschung, Zerbst, Germany, ⁸Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea, ⁹Centro de Investigación Farmacológica y Biotecnológica, Mexico City, Mexico, ¹⁰Rheumatology Department, Krasnoyarsk State Medical University, Krasnoyarsk, Russia, ¹¹CETI-Centro de estudos em Terapias Inovadoras, Universidade Federal do Parana, Curitiba, Brazil, ¹²Rheumatology, Eulji University Hospital, DaeJeon, South Korea, ¹³Division of Rheumatology, Department of Internal Medicine,, Inha University Hospital, Incheon, South Korea, ¹⁴Division of Rheumatology, Catholic University of Daegu School of Medicine, Daegu, South Korea, ¹⁵City Reumatology Center, Research Medical Complex Vashe Zdorovie, Kazan, Russia, ¹⁶CELLTRION, Inc., Incheon, South Korea, ¹⁷Department of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea, ¹⁸Allergy-Rheumatology, Ajou University Hospital, Suwon, South Korea

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: biosimilars, Clinical Response, rheumatoid arthritis (RA) and rituximab

Session Information

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Novel therapies, Biosimilars, Strategies and Mechanisms in Rheumatoid Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose CT-P10 is a biosimilar candidate for rituximab. Pharmacokinetic equivalence and similarity of clinical efficacy, safety and immunogenicity had been demonstrated between CT-P10 and Innovator Rituximab (RTX) groups¹. The immunogenicity to the biologic monoclonal antibody may affect both patient’s safety and therapeutic efficacy. Until now the presence of human anti-chimeric antibodies (HACA) to rituximab was known not to change the clinical efficacy and safety of rituximab.

The purpose of this analysis was to demonstrate the impact of anti‑drug antibody (ADA) on efficacy and safety of CT‑P10 and RTX in patients with rheumatoid arthritis (RA) over week 24.

Methods A total of 154 RA patients were randomized 2:1 to receive 2 infusions (1000 mg, 2 week interval) of either CT-P10 (n=103) or RTX (n=51), and efficacy, safety and immunogenicity were assessed during the study. Electrochemilumencent (ECL) assay was used to assess immunogenicity in this study since this assay is about 10 times more sensitive than the enzyme-linked immuno sorbent assay (ELISA) which was used in the historical rituximab trials.

The impact of ADA on efficacy and safety in both treatment groups was evaluated at week 24, when drug concentration was low enough not to interfere with the analysis.

Results The proportion of patients who developed ADA at week 24 was exactly same (17.6% each) in both CT-P10 and RTX treatment groups. Similar proportion of patients achieved ACR20 and the European League Against Rheumatism (EULAR-CRP and -ESR) responses after the CT-P10 and RTX treatment in both ADA (+) and (-) subgroups (Table 1). The interference of the ADA on the clinical response was not significant in both treatment groups.

The safety profiles of CT-P10 were generally comparable to those of RTX in both ADA (+) and (-) subgroups. The proportion of patients with adverse event (AE) were 55.6% and 49.4% for CT-P10-ADA (+) and (-) subgroups and 88.9% and 67.6% for RTX-ADA (+) and (-) subgroups, respectively. Serious AE was reported in 11.1% and 15.6% in the CT-P10-ADA (+) and (-) subgroups and 22.2% and 16.2% in the RTX-ADA (+) and (-) subgroups, respectively. The proportion of patients with AE due to infections and infusion related reactions was also similar between the treatment groups in ADA (+) and (-) subgroups.

Table 1. The Impact of ADA on Efficacy in Treatment Groups (%)

Clinical Response	CT-P10		RTX
Clinical Response	ADA (+)	ADA (-)	ADA (+)	ADA (-)
ACR20	61.1	67.5	62.5	75.0
EULAR response (CRP)	66.7	85.7	75.0	85.7
EULAR response (ESR)	61.1	80.5	75.0	80.0

Note: No statistical difference in all comparisons between ADA subgroups or treatment groups (p>0.05). EULAR (CRP/ESR): the proportion of patients with moderate or good response

Conclusion The development of ADA did not affect clinical response or safety profiles in RA patients treated with CT‑P10 or RTX, and the magnitude of impact of ADA was similar in both treatment groups. These results confirmed the comparability of CT-P10 to those of RTX in efficacy and safety over 24 weeks regardless of the immunogenic reaction.

Reference

Yoo DH, et al. Arthritis Rheum 2013;65(Suppl 10): S736

Disclosure:

D. H. Yoo,

CELLTRION, Inc.,

W. Park,

CELLTRION, Inc.,

S. Jeka,

CELLTRION, Inc.,

F. Cons Molina,

CELLTRION, Inc.,

P. Hrycaj,

CELLTRION, Inc.,

P. Wiland,

CELLTRION, Inc.,

W. Spieler,

CELLTRION, Inc.,

E. Y. Lee,

CELLTRION, Inc.,

F. G. Medina-Rodriguez,

CELLTRION, Inc.,

P. Shesternya,

CELLTRION, Inc.,

S. Radominski,

CELLTRION, Inc.,

D. H. Sheen,

CELLTRION, Inc.,

M. J. Lim,

CELLTRION, Inc.,

J. Y. Choe,

CELLTRION, Inc.,

L. Myasoutova,

CELLTRION, Inc.,

T. Kwon,

CELLTRION, Inc.,

S. J. Lee,

CELLTRION, Inc.,

S. C. Shim,

CELLTRION, Inc.,

C. H. Suh,

CELLTRION, Inc.,

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