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/100PY[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)]
TB disease by date of treatment initiation*	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.