Are All Oral COX-2 Selective Inhibitors the Same? A Consideration of Celecoxib, Etoricoxib, and Diclofenac

Table 3

GI safety of celecoxib and etoricoxib compared with diclofenac in patients with OA and RA.

Study	Reference	Celecoxib	Diclofenac	Etoricoxib
Retrospective pooled analyses
Discontinuations due to any GI AEs, n (%)	NIculescu et al, 2009 [41]	613 (4.2)	284 (5.0)
Discontinuations due to GI intolerability AEs, n (%)	NIculescu et al, 2009 [41]	510 (3.5)	235 (4.2)
Discontinuations due to GI AEs, n (%)	Mallen et al, 2011 [40]	283 (4.8)	115 (4.9)
Discontinuations due to GI intolerability AEs, n (%)	Mallen et al, 2011[40]	235 (4.0)	97 (4.2)
EDGE
Discontinuations due to GI AEs, per 100 PY	Baraf et al, 2007 [36]		19.2	9.4
HR (95% Cl)			0.50 (0.43–0.58)
EDGE II
Discontinuations due to GI AEs, per 100 PY	Krueger et al, 2008 [37]		8.5	5.2
HR (95% Cl)			0.62 (0.47–0.81)
MEDAL study (etoricoxib 60 mg OA cohort)
Discontinuations due to any clinical GI AEs, n (%)	Combe et al, 2009 [38]		369 (5.5)	213 (3.1)
Discontinuations due to any laboratory GI/liver AEs, n (%)	Combe et al, 2009 [38]		96 (1.4)	9 (0.1)
MEDAL program
Upper GI clinical events, per 100 PY (95% CI)	Cannon et al, 2006 [57]		0.97 (0.85–1.10)	0.67 (0.57–0.77)
HR (95% Cl)			0.69 (0.57–0.83)
Complicated upper GI clinical events, per 100 PY	Lane et al, 2007 [39]		0.32	0.30
n (%)			82 (0.47)	78 (0.45)
HR (95% Cl)			0.91 (0.67–1.24)
Uncomplicated upper GI clinical events, per 100 PY	Lane et al, 2007 [39]		0.65	0.37
n (%)			164 (0.95)	98 (0.56)
HR (95% Cl)			0.57 (0.45–0.74)
Lower GI clinical events, per 100 PY (95% Cl)	Lane et al, 2008 [45]		0.38 (0.31–0.46)	0.32 (0.25–0.39)
HR (95% Cl)			0.84 (0.63–1.13)
CONDOR
Clinically significant events throughout the GI tract, n (%)	Chan et al, 2010 [43]	20 (0.9)	81 (3.8)
HR (95% Cl)		4.3 (2.6–7.0)
Discontinued due to GI AEs, n (%)	Chan et al, 2010 [43]	114 (6.0)	167 (8.0)

In addition to GI safety, data from parts of the MEDAL clinical trial programs and the CLASS study demonstrated a significantly higher incidence of hepatic AEs with diclofenac than with either coxib comparator (celecoxib versus diclofenac: 0.6% and 2.3%, respectively, p ≤ 0.05; etoricoxib versus diclofenac: 4.3% and 9.4%, respectively, p ≤ 0.05) (Silverstein et al. 2000, Krueger et al. 2008).
GI intolerability AEs: abdominal pain, diarrhea, dyspepsia, flatulence, and nausea.
Celecoxib combined doses of 200 mg daily dose and 400 mg daily dose.
GI intolerability AEs: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, and nausea.
Clinical and laboratory GI AEs.
Bleeding from the esophagus, stomach, or duodenum; perforation or obstruction from a nonmalignant gastric or duodenal ulcer; or an ulcer documented on clinically indicated workup.
The MEDAL program consists of data from the MEDAL, EDGE I, and EDGE II trials.
Perforation, obstruction, and witnessed ulcer or significant bleeding.
Uncomplicated ulcer or bleeding.
Bleeding, perforation, obstruction.
Gastroduodenal, small-bowel, or large-bowel hemorrhage, gastric-outlet obstruction; gastroduodenal, small-bowel, or large-bowel perforation; clinically significant anemia of defined GI or presumed occult GI origin; acute GI hemorrhage of unknown origin.
p ≤ 0.05.
GI, gastrointestinal; OA, osteoarthritis; RA, rheumatoid arthritis; AEs, adverse events; PY, patient-years; HR, hazard ratio.