WARNING: RISK OF SERIOUS INFECTIONS
See full Prescribing Information for complete Boxed Warning.
*Actemra is represented by EU-approved tocilizumab in the study.
†The most commonly reported ARs in RA controlled studies up to 24 weeks (occurring in at least 5% of patients treated with tocilizumab-IV monotherapy or in combination with DMARDs).
For a detailed listing of ARs, please see Section 6 of Prescribing Information.
ALT=alanine aminotransferase.
For complete Warnings and Precautions, see full Prescribing Information.
Parameter | TOFIDENCE (N=45) |
EU-rTCZ (N=42) | US-rTCZ (N=42) |
P value† | TOFIDENCE/EU-rTCZ GMR (90% CI) |
TOFIDENCE/US-rTCZ GMR (90% CI) |
US-rTCZ/EU-rTCZ GMR (90% CI) |
---|---|---|---|---|---|---|---|
AUC0-∞ (μg*h/mL) | 10,840 (16.6) | 11,080 (19.5) | 10,690 (15.4) | 0.73 | 98.06 (92.10–104.41) |
100.82 (95.76–106.15) |
97.26 (91.75–103.10) |
AUC0-t (μg*h/mL) | 10,260 (17.8) | 10,580 (21.5) | 10,390 (16.4) | 0.78 | 97.39 (91.01–104.20) |
98.18 (92.89–103.78) |
99.19 (93.22–105.53) |
Cmax (μg/mL) | 88.28 (14.5) | 96.28 (17.6) | 91.29 (16.4) | 0.03 | 91.71 (86.90–96.79) |
96.25 (91.70–101.03) |
95.28 (90.04–100.82) |
Adapted from: Zhang et al. 2021.
*GeoMean (CV%)
†Bioequivalence by ANOVA if the 90% confidence intervals (CIs) for the ratio of geometric means (GMRs) of the treatments compared were contained within the pre-defined equivalence margin (80-125%).
ANOVA=analysis of variance; AUC0-t=area under the curve from zero to the final quantifiable concentration; AUC0–∞=area under the curve from zero to infinity; Cmax=maximum observable serum concentration; GMR=geometric mean ratio.
Summary of common TEAEs Number (%) of subjects |
|||||
---|---|---|---|---|---|
TOFIDENCE
(n=45) |
EU-Actemra
(n=42) |
US-Actemra
(n=42) |
Overall
(N=129) |
p* | |
Number of participants with treatment-related TEAEs | 27 (60.0) | 34 (81.0) | 32 (76.2) | 93 (72.1) | 0.07 |
Investigations | 21 (46.7) | 26 (61.9) | 27 (64.3) | 74 (57.4) | 0.19 |
Neutrophil count decreased | 12 (26.7) | 20 (47.6) | 25 (59.5) | 57 (44.2) | 0.007 |
White blood cell count decreased | 7 (15.6) | 12 (28.6) | 16 (38.1) | 35 (27.1) | 0.06 |
Alanine aminotransferase increased | 6 (13.3) | 10 (23.8) | 7 (16.7) | 23 (17.8) | 0.43 |
Aspartate aminotransferase increased | 7 (15.6) | 8 (19.0) | 3 (7.1) | 18 (14.0) | 0.26 |
Blood bilirubin increased | 0 (0.0) | 5 (11.9) | 4 (9.5) | 9 (7.0) | 0.07 |
Metabolism and nutrition disorders | 11 (24.4) | 15 (35.7) | 8 (19.0) | 34 (26.4) | 0.20 |
Hypertriglyceridemia | 9 (20.0) | 11 (26.2) | 6 (14.3) | 26 (20.2) | 0.39 | Hyperuricemia | 3 (6.7) | 4 (9.5) | 4 (9.5) | 11 (8.5) | 0.85 | Blood and lymphatic system disorders | 2 (4.4) | 3 (7.1) | 0 (0.0) | 5 (3.9) | 0.23 | Cardiac disorders | 0 (0.0) | 4 (9.5) | 1 (2.4) | 5 (3.9) | 0.06 | Infections and infestations | 1 (2.2) | 3 (7.1) | 1 (2.4) | 5 (3.9) | 0.40 |
Adapted from: Zhang et al. 2021.
p*, the number (%) of subjects with common TEAEs were compared among the three groups. Neutrophil count (p*=0.007). Other treatment-related emergent adverse events (p*>0.05).
Parameter | Time (day) |
TOFIDENCE (n=45) |
EU-Actemra (n=42) |
US-Actemra (n=42) |
Overall (n=129) |
p* |
---|---|---|---|---|---|---|
ADA | 0 | 2 (4.4) | 0.0 | 0.0 | 2 (1.6) | 0.15 |
15 | 3 (6.7) | 3 (7.1) | 3 (7.1) | 9 (7.0) | 0.99 | |
43 | 11 (24.4) | 9 (21.4) | 9 (21.4) | 29 (22.5) | 0.92 | |
57 | 19 (42.2) | 10 (23.8) | 12 (28.6) | 41 (31.8) | 0.15 | |
NAb | 0 | 1 (2.2) | 0.0 | 0.0 | 1 (0.8) | 0.39 |
15 | 3 (6.7) | 3 (7.1) | 3 (7.1) | 9 (7.0) | 0.99 | |
43 | 10 (22.2) | 6 (14.3) | 8 (19.0) | 24 (18.6) | 0.63 | |
57 | 14 (31.1) | 9 (21.4) | 12 (28.6) | 35 (27.1) | 0.57 |
Adapted from: Zhang et al. 2021.
The positive rates of ADA and NAb were compared among the three groups.
ADA=antidrug antibody; NAb=neutralizing antibody.
Weeks 0-24 (Treatment Period 1)3 | Weeks 24-48 (Treatment Period 2) and up to Week 52 (Safety Set)4 | ||||
---|---|---|---|---|---|
n (%) | TOFIDENCE
(n=312) |
Actemra*
(n=309) |
TOFIDENCE
(n=290) |
Actemra*
TOFIDENCE (n=142 |
Actemra*
(n=145) |
TEAE | 201 (64) | 196 (63) | 162 (56) | 92 (65) | 90 (62) |
Treatment-related TEAE | 148 (47) | 151 (49) | 112 (39) | 64 (45) | 59 (41) |
Serious TEAE | 11 (4) | 13 (4) | 8 (3) | 5 (4) | 4 (3) |
Treatment-related serious TEAE | 2 (1) | 7 (2) | 2 (<1) | 1 (<1) | 1 (<1) |
Fatal TEAE | 3 (1) | 1 (<1) | 0 | 0 | 0 |
ADA-positive | 64 (21) | 42 (14) | 61 (21) | 23 (16) | 27 (19) |
NAb-positive | 64 (21) | 42 (14) | 61 (21) | 23 (16) | 26 (18) |
Adapted from: Zhang et al. 2021.
*Actemra is represented by EU-approved tocilizumab in the study.
TEAE=treatment-emergent adverse event.
Safety set included all randomly assigned patients that had received study drug in Treatment Period 1 or Treatment Period 2, respectively.
Adapted from: Leng, et al. 2024
*Actemra is represented by EU-approved tocilizumab in the study.
Nonserious TEAEs with an occurrence below 5% in either group are not reported here.
Total reports of any adverse event were comparable between TOFIDENCE 66% (n=206) and Actemra 65% (n=201)3
The occurrence of all TEAEs was 64% (n=201) for TOFIDENCE and 63% (n=196) for Actemra3
Adapted from: Zhang et al. 2024.
*Actemra is represented by EU-approved tocilizumab in the study.
Nonserious TEAEs with an occurrence below 5% in either group are not reported here.
†None of the individual reported serious TEAEs (or treatment-related serious TEAEs) had an incidence higher than 0.5% across all enrolled participants that had received study drug.
ALT=alanine aminotransferase; DMARD=disease-modifying anti-rheumatic drug; NAb=neutralizing antibody; TEAE=treatment-emergent adverse event.