Table 3.
Summary of AEs of interest reported for PBO-controlled and CZP-treated patients (all doses) in the RCT period
| Overall | RA | axSpA | PsA | PSO | CD | ||||||||
| RCT PBO (n=3092; 1184 PY) |
RCT CZP (n=6467; 3017 PY) |
RCT PBO (n=1759; 775 PY) |
RCT CZP (n=4248; 2260 PY) |
RCT PBO (n=107; 39 PY) |
RCT CZP (n=218; 99 PY) |
RCT PBO (n=136; 51 PY) |
RCT CZP (n=273; 122 PY) |
RCT PBO (n=215; 59 PY) |
RCT CZP (n=809; 237 PY) |
RCT PBO (n=875; 262 PY) |
RCT CZP (n=919; 299 PY) |
||
| Mean exposure (years) | 0.38 | 0.47 | 0.44 | 0.53 | 0.36 | 0.45 | 0.37 | 0.45 | 0.27 | 0.29 | 0.30 | 0.33 | |
| Median exposure (years) | 0.31 | 0.38 | 0.31 | 0.46 | 0.31 | 0.46 | 0.32 | 0.46 | 0.31 | 0.31 | 0.23 | 0.31 | |
| IR/100 PY[n(%)] | |||||||||||||
| SIEs | 2.46 [29 (0.9)] |
4.83 [144 (2.2)] |
2.08 [16 (0.9)] |
4.88 [109 (2.6)] |
0 | 2.03 [2 (0.9)] |
1.98 [1 (0.7)] |
3.30 [4 (1.5)] |
0 | 2.11 [5 (0.6)] |
4.63 [12 (1.4)] |
8.15 [24 (2.6)] |
|
| OIs including TB disease | 0.08 [1 (0.0)] |
0.76 [23 (0.4)] |
0.13 [1 (0.1)] |
0.89 [20 (0.5)] |
0 | 0 | 0 | 0.82 [1 (0.4)] |
0 | 0.42 [1 (0.1)] |
0 | 0.34 [1 (0.1)] |
|
| All TB disease | 0 | 0.46 [14 (0.2)] |
0 | 0.53 [12 (0.3)] |
0 | 0 | 0 | 0 | 0 | 0.42 [1 (0.1)] |
0 | 0.34 [1 (0.1)] |
|
| TB disease by date of treatment initiation* | Pre-2007 | 0 | 0.86 [11 (0.4)] |
0 | 0.91 [9 (0.5)] |
N/A | N/A | N/A | N/A | 0 | 3.81 [1 (0.9)] |
0 | 0.39 [1 (0.1)] |
| 2007 onwards | 0 | 0.17 [3 (0.1)] |
0 | 0.24 [3 (0.1)] |
0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Herpes zoster | 0 | 0.13 [4 (0.1)] |
0 | 0.13 [3 (0.1)] |
0 | 0 | 0 | 0.82 [1 (0.4)] |
0 | 0 | 0 | 0 | |
| All malignancies | 0.76 [9 (0.3)] |
0.63 [19 (0.3)] |
0.65 [5 (0.3)] |
0.71 [16 (0.4)] |
0 | 0 | 1.98 [1 (0.7)] |
0 | 0 | 0.42 [1 (0.1)] |
1.15 [3 (0.3)] |
0.67 [2 (0.2)] |
|
| All malignancies excluding NMSC | 0.68 [8 (0.3)] |
0.46 [14 (0.2)] |
0.52 [4 (0.2)] |
0.58 [13 (0.3)] |
0 | 0 | 1.98 [1 (0.7)] |
0 | 0 | 0 | 1.15 [3 (0.3)] |
0.33 [1 (0.1)] |
|
| Melanoma | 0.08 [1 (0.0)] |
0.03 [1 (0.0)] |
0.13 [1 (0.1)] |
0.04 [1 (0.0)] |
0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Lymphoma, including Hodgkin’s disease† | 0.08 [1 (0.0)] |
0.07 [2 (0.0)] |
0 | 0.09 [2 (0.0)] |
0 | 0 | 0 | 0 | 0 | 0 | 0.38 [1 (0.1)] |
0 | |
| NMSC | 0.08 [1 (0.0)] |
0.17 [5 (0.1)] |
0.13 [1 (0.1)] |
0.13 [3 (0.1)] |
0 | 0 | 0 | 0 | 0 | 0.42 [1 (0.1)] |
0 | 0.34 [1 (0.1)] |
|
| MACE | 0.34 [4 (0.1)] |
0.76 [23 (0.4)] |
0.52 [4 (0.2)] |
0.84 [19 (0.4)] |
0 | 0 | 0 | 2.47 [3 (1.1)] |
0 | 0.42 [1 (0.1)] |
0 | 0 | |
| GI perforations | 0.08 [1 (0.0)] |
0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.38 [1 (0.1)] |
0 | |
| New onset or worsening psoriasis‡ | 0 | 0.03 [1 (0.0)] |
0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.42 [1 (0.1)] |
0 | 0 | |
| Venous thromboembolism§ | 0.42 [5 (0.2)] |
0.30 [9 (0.1)] |
0.52 [4 (0.2)] |
0.35 [8 (0.2)] |
0 | 0 | 0 | 0 | 1.71 [1 (0.5)] |
0 | 0 | 0.33 [1 (0.1)] |
|
| Pulmonary embolism (SAEs only) | 0.25 [3 (0.1)] |
0.10 [3 (0.0)] |
0.39 [3 (0.2)] |
0.09 [2 (0.0)] |
0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.33 [1 (0.1)] |
|
n (%) refers to the number of patients with events; zeros indicate that there were no cases. NMSC includes serious and non-serious cases.
*Before 2007, a positive TB result on the PPD tuberculin skin test varied (from ≥5 to ≥20 mm) according to geographic region. Since 2007, CZP recommendations internationally mandate that all patients with PPD ≥5 mm receive treatment for latent TB infection. There were no patients with axSpA or PsA enrolled prior to 2007.
†Lymphoma cases include one case of Hodgkin’s disease in a CZP-treated CD patient.
‡Worsening psoriasis defined as psoriasis reported as an adverse event in a patient enrolled in a PSO study; new-onset psoriasis defined as psoriasis in a patient enrolled in a non-PSO study.
§Includes serious and non-serious deep vein thrombosis and pulmonary embolism events.
AE, adverse events; axSpA, axial spondyloarthritis; CD, Crohn’s disease; CZP, certolizumab pegol; GI, gastrointestinal;IR, incidence rate (the number of new cases per 100 PY, with the denominator being the exposure duration up to the first occurrence of a particular AE);MACE, major adverse cardiovascular events;NMSC, non-melanoma skin cancer;OI, opportunistic infection;OLE, open-label extension;PBO, placebo; PPD, purified protein derivative; PsA, psoriatic arthritis; PSO, psoriasis; PY, patient-years; RA, rheumatoid arthritis;RCT, randomised controlled trial;SAE, serious adverse event;SIE, serious infectious event;TB, tuberculosis.