Safety and efficacy of CT-P13 in Japanese patients with rheumatoid arthritis in an extension phase or after switching from infliximab

Figures & data

Figure 1. Patient disposition in the phase I/II study and the extension study.

Table 1. Baseline patient demographics and disease characteristics—safety analysis set.

Characteristics	CT-P13 throughout study (n = 38)		Switched from IFX to CT-P13 (n = 33)
	Phase I/II*	Extension†	Phase I/II*	Extension†
Age (years), mean ± SD‡	53.4 ± 12.4	54.5 ± 12.4	56.1 ± 10.7	57.2 ± 10.7
Gender (male/female), n (%)‡	8 (21.1)/30 (78.9)		7 (21.2)/26 (78.8)
Body weight (kg), mean ± SD	57.3 ± 10.2	59.2 ± 10.6	53.9 ± 9.3	54.7 ± 9.8
Duration of disease (years), mean ± SD‡	7.6 ± 8.0	8.8 ± 8.0	9.0 ± 7.8	10.1 ± 7.8
CRP (mg/dL), mean ± SD	2.18 ± 1.74	1.04 ± 2.00	1.90 ± 2.38	0.79 ± 1.45
≤2 mg/dL, n (%)	22 (57.9)	32 (84.2)	22 (66.7)	30 (90.9)
>2 mg/dL, n (%)	16 (42.1)	6 (15.8)	11 (33.3)	3 (9.1)
ESR (mm/h), mean ± SD	55.7 ± 28.0	31.7 ± 26.4	51.4 ± 19.5	33.0 ± 20.5
Steinbrocker class
Class I, n (%)	3 (7.9)	12 (31.6)	4 (12.1)	9 (27.3)
Class II, n (%)	29 (76.3)	24 (63.2)	26 (78.8)	22 (66.7)
Class III, n (%)	6 (15.8)	2 (5.3)	3 (9.1)	2 (6.1)
Class IV, n (%)	0	0	0	0
Tender joint count (0–68), mean ± SD	14.3 ± 10.6	2.5 ± 5.0	14.8 ± 10.1	3.8 ± 5.4
Swollen joint count (0–66), mean ± SD	12.5 ± 7.8	4.0 ± 5.0	12.8 ± 7.7	4.1 ± 5.2
Patient’s assessment of pain (VAS, 0–100), mean ± SD	52.7 ± 24.5	18.4 ± 18.7	45.4 ± 22.7	27.8 ± 22.7
Patient’s global assessment of disease activity (VAS, 0–100), mean ± SD	56.9 ± 23.5	19.6 ± 19.0	47.2 ± 23.5	27.0 ± 21.9
Physician’s global assessment of disease activity (VAS, 0–100), mean ± SD	53.0 ± 19.0	19.1 ± 16.0	49.5 ± 18.0	23.2 ± 20.4
DAS28 (ESR), mean ± SD	5.967 ± 1.062	3.267 ± 1.343	5.881 ± 0.799	3.801 ± 1.454
DAS28 (CRP), mean ± SD	5.226 ± 1.071	2.574 ± 1.230	5.034 ± 0.883	2.986 ± 1.432
SDAI, mean ± SD	31.62 ± 13.91	9.45 ± 9.49	31.17 ± 10.61	12.46 ± 11.61
CDAI, mean ± SD	29.44 ± 13.20	8.42 ± 8.16	29.27 ± 10.09	11.68 ± 11.07
HAQ-DI, mean ± SD	1.05 ± 0.63	0.36 ± 0.34	0.92 ± 0.50	0.56 ± 0.54
ADA positive, n (%)		12 (31.6)		16 (48.5)

ADA, anti-drug antibodies; CDAI, clinical disease activity index; CRP, C reactive protein; DAS28 (CRP), disease activity score using a 28-joint count and CRP level; DAS28 (ESR), disease activity score using a 28-joint count and ESR; ESR, erythrocyte sedimentation rate; FAS, full analysis set; HAQ-DI, Health Assessment Questionnaire disability index; IFX, innovator infliximab; SDAI, simplified disease activity index; VAS, visual analog scale.

*Baseline value in Phase I/II study; †value at 62W (0xW) as baseline in extension study; ‡baseline value in Phase I/II study expressed.

Table 2. Summary of safety—safety analysis set.

	CT-P13 throughout study (n = 38)		Switched from IFX to CT-P13 (n = 33)
	Phase I/II, n (%)	Extension, n (%)	Phase I/II, n (%)	Extension, n (%)
Any AE	33 (86.8)	34 (89.5)	29 (87.9)	29 (87.9)
Any ADR	32 (84.2)	34 (89.5)	27 (81.8)	26 (78.8)
Serious AE	1 (2.6)	2 (5.3)	3 (9.1)	4 (12.1)
AE leading to study discontinuation	NA	4 (10.5)	NA	8 (24.2)
Any infectious disease	21 (55.3)	21 (55.3)	16 (48.5)	17 (51.5)
Infusion-related reaction*	4 (10.5)	2 (5.3)	5 (15.2)	4 (12.1)
Administration postponed	6 (15.8)	3 (7.9)	4 (12.1)	1 (3.0)
Intermittence of drop infusion	1 (2.6)	3 (7.9)	1 (3.0)	3 (9.1)

AE, adverse event; ADR, adverse drug reaction; IFX, innovator infliximab; NA, not applicable.

*Includes a patient who experienced anaphylactic shock during the infusion of the study drug.

Table 3. SAEs and AEs leading to study discontinuation occurred in extension phase—safety analysis set.

Adverse events	CT-P13 throughout study (n = 38), n (%)	Switched from IFX to CT-P13 (n = 33), n (%)
Serious AE	2 (5.3)	4 (12.1)
Enterocolitis		1 (3.0)
Tendon rupture		1* (3.0)
Infusion-related reaction	1 (2.6)
Weight decreased	1* (2.6)
Colon cancer		1 (3.0)
Interstitial lung disease		1 (3.0)
AE leading to study discontinuation	4 (10.5)	8 (24.2)
Pancytopenia		1* (3.0)
Anaphylactic shock	1 (2.6)
Anti-neutrophil cytoplasmic  antibody positive vasculitis	1 (2.6)
Pneumonia		1 (3.0)
Infusion-related reaction	1 (2.6)	3 (9.1)
Interferon-γ release assays positive	1 (2.6)
Rheumatoid arthritis		1* (3.0)
Colon cancer		1 (3.0)
Interstitial lung disease		1 (3.0)

AE, adverse event; IFX, innovator infliximab.

*Not related to study drug.

Table 4. Adverse events reported in at least 5% of patients in either of the treatment groups—safety analysis set.

	CT-P13 throughout study (n = 38)				Switched from IFX to CT-P13 (n = 33)
	Severity				Severity
Adverse events	Total n (%)	Mild	Moderate	Severe	Total n (%)	Mild	Moderate	Severe
Chronic gastritis					2 (6.1)	2
Constipation	2 (5.3)	2			2 (6.1)	2
Gastrooesophageal reflux disease	3 (7.9)	3			1 (3.0)	1
Nausea	3 (7.9)	3			1 (3.0)	1
Stomatitis	2 (5.3)	2
Pyrexia	2 (5.3)	2
Hepatic function abnormal	3 (7.9)	3
Bronchitis	3 (7.9)	2	1		1 (3.0)	1
Conjunctivitis	2 (5.3)	2
Gastroenteritis	2 (5.3)	2			1 (3.0)		1
Herpes zoster	4 (10.5)	2	2		1 (3.0)	1
Influenza	3 (7.9)	3
Nasopharyngitis	10 (26.3)	10			9 (27.3)	9
Otitis media	2 (5.3)	2
Paronychia	1 (2.6)	1			2 (6.1)	2
Pharyngitis	2 (5.3)	2			2 (6.1)	2
Pneumonia	2 (5.3)	2			2 (6.1)	1	1
Sinusitis	2 (5.3)	2
Enteritis infectious					2 (6.1)	2
Oral herpes	2 (5.3)	2
Tendon rupture					2 (6.1)		2
Infusion-related reaction	1 (2.6)			1	4 (12.1)	3	1
ALT increased	3 (7.9)	3			1 (3.0)	1
AST increased	2 (5.3)	2			2 (6.1)	2
Gamma GTP increased					2 (6.1)	2
WBC decreased	2 (5.3)	2
Double stranded DNA antibody positive	2 (5.3)	2			2 (6.1)	2
Osteoporosis	1 (2.6)	1			4 (12.1)	3	1
Rheumatoid arthritis					3 (9.1)	1	2
Spinal osteoarthritis					2 (6.1)	1		1
Headache	3 (7.9)	3			1 (3.0)	1
Upper respiratory tract inflammation	8 (21.1)	7	1		2 (6.1)	2
Oropharyngeal pain	2 (5.3)	2			1 (3.0)	1
Eczema	3 (7.9)	3			1 (3.0)	1
Rash	4 (10.5)	4			1 (3.0)	1
Asteatosis	2 (5.3)	2
Hypertension	2 (5.3)	2

IFX, innovator infliximab.

Figure 2. Changes in ADA status at baseline and Week 110 (48×) and the relationship between ADA status and dose of CT-P13 in patients who maintained the CT-P13 treatment throughout study (n = 38) and patients who switched from IFX to CT-P13 (n = 33) in the safety analysis set.

Figure 3. Changes after dose-increase in DAS28 for patients who maintained the CT-P13 treatment throughout the study (solid circle; n = 23) and patients who switched from IFX to CT-P13 (open circle, n = 16). (A) DAS28 (ESR) in the FAS without LOCF and NRI. (B) DAS28 (ESR) in the FAS with the missing data imputed by the LOCF and NRI method. (C) DAS28 (CRP) in the FAS without LOCF and NRI. (D) DAS28 (CRP) in the FAS with the missing data imputed by the LOCF and NRI method. “0*” denotes the time of dose-increase.