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Abstract Number: 2514

Development of a Subcutaneous Formulation of CT-P13 (Infliximab): Maintenance Subcutaneous Administration May Elicit Lower Immunogenicity Compared to Intravenous Treatment

Dae-Hyun Yoo1, René Westhovens2, S. Ben-Horin3, W. Reinisch4, S. Schreiber5, B.D. Ye6, Sang-Joon Lee7, J.H. Suh7 and M.R. Kim7, 1Department of Rheumatology, Hospital for Rheumatic Diseases Hanyang University, Seoul, Korea, Republic of (South), 2Rheumatology, University Hospital KU Leuven, Leuven, Belgium, 3University of Tel Aviv Sheba Medical Center, Tel-Hashomer, Israel, 4Medical University of Vienna, Vienna, Austria, 5University Hospital Schleswig-Holstein, Kiel, Germany, 6Department of Gastroenterology and Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, Republic of (South), 7CELLTRION, Inc., Incheon, Korea, Republic of (South)

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Crohn's Disease, infliximab and rheumatoid arthritis (RA)

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Session Information

Date: Tuesday, October 23, 2018

Session Title: Rheumatoid Arthritis – Treatments Poster III: Biosimilars and New Compounds

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Intravenous (IV) use of CT-P13, an infliximab (INX) biosimilar, has resulted in comparable efficacy, safety and immunogenicity as innovator INX in various indications including rheumatoid arthritis (RA)1 and Crohn’s disease (CD)2. A subcutaneous (SC) formulation of CT-P13 is developed to provide patients with opportunities for self-injection, thereby enhancing convenience and flexibility in treatment. This work aimed to investigate immunogenicity by post-hoc analysis of two randomized controlled trials comparing pharmacokinetics of CT-P13 IV and CT-P13 SC.

Methods: Patients with RA (6 or more swollen and tender joints and serum C-reactive protein [CRP] concentration >0.6 mg/dL) and active CD (Crohn’s Disease Activity Index [CDAI] score of 220 – 450) were treated with CT-P13 IV at Weeks 0 and 2. At Week 6, patients were randomized for continuation with IV or SC administration. The IV cohorts received CT-P13 IV (3 mg/kg for RA and 5 mg/kg for CD) every 8 weeks and the SC cohorts were treated with CT-P13 SC (90, 120, 180 mg for RA and 120, 180 and 240 mg for CD) every 2 weeks up to Week 30. Trough serum concentrations (Ctrough) were assessed at Weeks 6, 14 and 22 for IV and Weeks 6, 8, 10, 14, 22, 24, 26 and 28 for SC. Target exposure level was considered as 1 µg/mL for RA3, 4 and 5 µg/mL for CD5, 6. Anti-drug antibody (ADA) was assessed before study drug administration at Weeks 0, 6, 14, 22 and 30 by a drug-sensitive, enzyme-linked immunosorbent assay.

Results: In total, 92 patients were randomized at Week 6 to IV (RA: n=13, CD: n=13) or SC (RA: n=35, CD: n=31). All RA patients used methotrexate as concomitant medication throughout the study. Among CD patients, immunomodulators were used at Week 6 by 9 (69.2%) and 15 (48.4%) patients in IV and SC cohorts, respectively. Efficacy results (EULAR [CRP] responder rate for RA and CDAI-70 responder rate for CD) were comparable between the IV and SC. Systemic safety profiles observed from CT-P13 SC after randomization were also comparable to those of IV. A sub-therapeutic Ctrough level below target exposure was detected at least once in 23 (92.0%) and 9 (14.1%) patients in IV and SC cohorts, respectively. ADA were detected at least once in 16 (64.0%) versus 11 (18.1%) of patients in the IV and SC cohorts (p<0.0001), respectively.

Table          Efficacy, Ctrough and immunogenicity among RA and CD patients

Efficacy

IV cohort

SC cohort

p value a

EULAR (CRP) responder rate

at Week 30 in RA patients

12/13 (92.3%)

32/32 (100%)

0.2889

CDAI-70 responder rate

at Week 30 in CD patients

8/10 (80.0%)

24/26 (92.3%)

0.3048

Ctrough

IV cohort

(N=25)

SC cohort

(N=64)

p value a

Ctrough< target exposure at least once

23 (92.0%)

9 (14.1%)

<0.0001

Ctrough>=target exposure throughout the study

2 (8.0%)

55 (85.9%)

Immunogenicity

IV cohort

SC cohort

p value a

Anti-drug antibody positive

at least once

16/25 b (64.0%)

11/61 b (18.1%)

<0.0001

RA patients

9/13 (69.2%)

8/33 b (24.2%)

0.0071

CD patients

7/12 b (58.3%)

3/28 b (10.7%)

0.0033

Note: a p value was derived from Fisher’s exact test. b Patients who reported ADA positive at Week 0 or 6 (before randomization) were excluded.

Conclusion: After initial loading two doses of CT-P13 IV, patients subsequently receiving biweekly maintenance treatment with CT-P13 SC achieve more stable steady state therapeutic blood levels of INX and have lower rate of ADA compared with patients receiving continued IV treatment. Further work to corroborate these findings is ongoing through a confirmatory efficacy trial.

References: 1 Yoo, et al. Arthritis Res Ther 2016;18:82.

2 Kim, et al. Gastroenterol J. 2017; 1138-1150.

3 Takeuchi, et al. Mod Rheumatol. 2009; 478-487.

4 Mori S. Mod Rheumatol. 2007; 83-91.

5 Papamichael, et al. Inflamm. Bowel Dis. 2015; 182–197.

6 Vaughn, et al. Inflamm. Bowel Dis. 2015; 1435-42.


Disclosure: D. H. Yoo, research support, 2, 5, 6; R. Westhovens, research support, 2, 6,Consultant, 5; S. Ben-Horin, consultancy, 5, 6,research support, 2; W. Reinisch, research funding, 2, 6, 8; S. Schreiber, consultancies and lecture fees, 5, 8; B. D. Ye, consultant, 6; S. J. Lee, employee, 3; J. H. Suh, employee, 3; M. R. Kim, employee, 3.

To cite this abstract in AMA style:

Yoo DH, Westhovens R, Ben-Horin S, Reinisch W, Schreiber S, Ye BD, Lee SJ, Suh JH, Kim MR. Development of a Subcutaneous Formulation of CT-P13 (Infliximab): Maintenance Subcutaneous Administration May Elicit Lower Immunogenicity Compared to Intravenous Treatment [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/development-of-a-subcutaneous-formulation-of-ct-p13-infliximab-maintenance-subcutaneous-administration-may-elicit-lower-immunogenicity-compared-to-intravenous-treatment/. Accessed May 17, 2022.
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