Table 2.
Summary of AEs of interest reported for CZP-treated patients (all doses) in the combined RCT and OLE periods (RCT+OLE)
| Overall (n=11 317; 21 695 PY) |
RA (n=6927; 13 542 PY) |
axSpA (n=315; 978 PY) |
PsA (n=393; 1316 PY) |
PSO (n=1112; 1481 PY) |
CD (n=2570; 4378 PY) |
||
| Mean exposure (years) | 1.92 | 1.95 | 3.10 | 3.35 | 1.33 | 1.70 | |
| Median exposure (years) | 1.15 | 1.13 | 3.75 | 3.99 | 1.51 | 0.86 | |
| IR/100 PY [n (%)] | |||||||
| SIEs* | 3.62 [757 (6.7)] |
3.44 [450 (6.5)] |
1.67 [16 (5.1)] |
1.64 [21 (5.3)] |
1.50 [22 (2.0)] |
5.97 [248 (9.6)] |
|
| OIs including TB disease | 0.39 [85 (0.8)] |
0.51 [69 (1.0)] |
0.10 [1 (0.3)] |
0.08 [1 (0.3)] |
0.14 [2 (0.2)] |
0.27 [12 (0.5)] |
|
| All TB disease | 0.29 [62 (0.5)] |
0.38 [51 (0.7)] |
0.10 [1 (0.3)] |
0 | 0.14 [2 (0.2)] |
0.18 [8 (0.3)] |
|
| TB disease by date of treatment initiation† | Pre-2007 | 0.42 [50 (1.1)] |
0.52 [42 (1.8)] |
N/A | N/A | 1.46 [1 (0.9)] |
0.19 [7 (0.3)] |
| 2007 onwards | 0.12 [12 (0.2)] |
0.17 [9 (0.2)] |
0.10 [1 (0.3)] |
0 | 0.07 [1 (0.1)] |
0.13 [1 (0.2)] |
|
| Herpes zoster | 0.06 [14 (0.1)] |
0.07 [10 (0.1)] |
0.10 [1 (0.3)] |
0.08 [1 (0.3)] |
0 | 0.05 [2 (0.1)] |
|
| All malignancies | 0.82 [178 (1.6)] |
0.93 [125 (1.8)] |
0.51 [5 (1.6)] |
0.46 [6 (1.5)] |
0.68 [10 (0.9)] |
0.73 [32 (1.2)] |
|
| All malignancies excluding NMSC | 0.66 [144 (1.3)] |
0.77 [104 (1.5)] |
0.41 [4 (1.3)] |
0.46 [6 (1.5)] |
0.47 [7 (0.6)] |
0.53 [23 (0.9)] |
|
| Melanoma | 0.06 [12 (0.1)] |
0.06 [8 (0.1)] |
0 | 0 | 0 | 0.09 [4 (0.2)] |
|
| Lymphoma, including Hodgkin’s disease‡ | 0.06 [13 (0.1)] |
0.07 [10 (0.1)] |
0 | 0.08 [1 (0.3)] |
0.07 [1 (0.1)] |
0.02 [1 (0.0)] |
|
| NMSC | 0.17 [37 (0.3)] |
0.16 [22 (0.3)] |
0.10 [1 (0.3)] |
0 | 0.20 [3 (0.3)] |
0.25 [11 (0.4)] |
|
| MACE | 0.47 [101 (0.9)] |
0.62 [84 (1.2)] |
0.10 [1 (0.3)] |
0.54 [7 (1.8)] |
0.27 [4 (0.4)] |
0.11 [5 (0.2)] |
|
| GI perforations | 0.08 [17 (0.2)] |
0.04 [5 (0.1)] |
0 | 0 | 0 | 0.27 [12 (0.5)] |
|
| New onset or worsening psoriasis§ | 0.03 [6 (0.1)] |
0 | 0.10 [1 (0.3)] |
0 | 0.27 [4 (0.4)] |
0.02 [1 (0.0)] |
|
| Venous thromboembolism¶ | 0.23 [49 (0.4)] |
0.27 [37 (0.5)] |
0 | 0.31 [4 (1.0)] |
0.14 [2 (0.2)] |
0.14 [6 (0.2)] |
|
| Pulmonary embolism (SAEs only) | 0.09 [20 (0.2)] |
0.11 [15 (0.2)] |
0 | 0.23 [3 (0.8)] |
0.07 [1 (0.1)] |
0.02 [1 (0.0)] |
|
n (%) refers to the number of patients with events; zeros indicate that there were no cases. NMSC includes serious and non-serious cases.
*Including the five appendicitis events confirmed as SIEs during the previous safety update in RA.18
†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 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 two cases of Hodgkin’s disease, one in RA and one in PSO.
§Worsening psoriasis defined as psoriasis reported as an AE 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 event; 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; 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.