Efficacy and safety of celecoxib on the incidence of recurrent colorectal adenomas: a systematic review and meta-analysis

Figures & data

Table 1 RCTs reporting incidence of recurrent colorectal adenomas

Reference year	Study name	Design	Treatment duration (years)	Follow-up colonoscopy	Subjects	Study group (n originally randomized)	Efficacy outcomes (n/N)		Safety outcomes (n/N)					High CV risk, n (%)a
							Advanced adenomas	Any adenomas	CRC	Mortality (any causes)	Serious adverse events	Renal-hypertensive disorders	Serious CV eventsa
Arber et al, 2006^Citation23	PreSAP	Multicenter, double-blind, placebo-controlled, RCT, parallel two-arm	3	At year 1, year 3, or both	Median age 61; 66% males	Celecoxib 400 mg once daily (n=933)	42/840	270/840	6/933	11/933	186/933	193/933	23/933	575 (37)
						Placebo (n=628)	56/557	264/557	1/628	7/628	106/628	96/628	12/628
Bertagnolli et al, 2006^Citation24	APC	Multicenter, double-blind, placebo-controlled, RCT, parallel three-arm	3	At year 1, year 3, or both	Median age 59; 68% males	Celecoxib 200 mg twice daily (n=685)	44/613	252/613	0/685	8/685	139/685	164/685	20/685	962 (47)
						Celecoxib 400 mg twice daily (n=671)	35/601	213/601	4/671	10/671	154/671	141/671	27/671
						Placebo (n=679)	99/608	354/608	3/679	6/679	127/679	130/679	8/679
Thompson et al, 2016^Citation41	Sel/Cel	Multicenter, double-blind, placebo-controlled, RCT, 2×2 factorial	1b	Within 1 year of discontinuing interventionc	Mean age 63; 68% males	Celecoxib 400 mg once daily (n=414)	3/119d	34/123	NA	NA	104/414	55/414	35/414	418 (51)
						Placebo (n=410)	12/119d	50/121	NA	NA	93/410	43/410	38/410

Notes:

a Adjudicated data from Solomon et al.;¹⁹

b Study reported the median time for taking placebo and intervention, respectively, was 13.6 and 14.2 months;

c Efficacy outcomes at different time intervals were reported after discontinuing intervention; as per our protocol, we have used data from subjects undergoing colonoscopy within 1 year of discontinuing intervention;

d Advanced status uncertain for six participants. n= number of events; N= number of participants.

Abbreviations: APC, Adenoma Prevention with Celecoxib trial; CRC, colorectal cancer; CV, cardiovascular; PreSAP, Prevention of Colorectal Sporadic Adenomatous Polyps Study; RCT, randomized controlled trial; Sel/Cel, Selenium and Celecoxib (Sel/Cel) Trial; NA, not available.

Table 2 Studies reporting posttreatment effect of celecoxib on incidence of recurrent colorectal adenomas after 2 years of off-treatment

Reference, year	Study name	Design	Subjects	Treatment duration (years)	Follow-up colonoscopy	Duration of off-treatment (years)	Study group (N, originally randomized)	Subjects completed follow-up colonoscopy, n	Efficacy outcomesa (n/N)
									Any adenomas	Advanced adenomas
Arber et al, 2011^Citation30	5-year analysis of PreSAP	Follow-up of double-blind, placebo-controlled RCT; multicenter; parallel two-arm	Mean age 60; 66% males	3	5	2	Celecoxib 400 mg/day (n=933)	508	186/508	NA
							Placebo (n=628)	347	86/347	NA
Bertagnolli et al, 2009^Citation31	5-year analysis of APC	Follow-up of double-blind, placebo-controlled RCT; multicenter; parallel three-arm	Median age 59; 71% males	3	5	2	Celecoxib 400 mg/day (n=685)	207	83/207	13/207
							Celecoxib 800 mg/day (n=671)	218	90/218	22/219
							Placebo (n=679)	214	79/214	11/214
Thompson et al, 2016^Citation41	Sel/Cel	Follow-up of double-blind, placebo-controlled RCT; multicenter; 2×2 factorial	Median age 59; 71% males	1b	5.5c	~4	Celecoxib 400 mg/day (n=414)	329	124/329	28/319d
							Placebo (n=410)	336	135/336	32/332d

Notes:

a Arber et al, 2011³⁰ – efficacy outcomes from 855 subjects who had colonoscopy at year 5, even if they had one or more new adenomas detected at any time after baseline; Bertagnolli et al, 2009³¹ – efficacy outcomes from 639 subjects in the extension study with any adenoma detected at the year 5 colonoscopy; Thompson et al, 2016⁴¹ – efficacy outcomes from 447 subjects with a follow-up colonoscopy within 3.5 years of qualifying colonoscopy.

b Study reported that the median time for taking placebo and intervention, respectively, was 13.6 and 14.2 months.

c Reported efficacy outcomes from follow-up colonoscopy within 5.5 years.

d Number of advanced adenomas uncertain for some participants.

Abbreviations: APC, Adenoma Prevention with Celecoxib trial; PreSAP, Prevention of Colorectal Sporadic Adenomatous Polyps Study; RCTs, randomized controlled trials; Sel/Cel, Selenium and Celecoxib (Sel/Cel) Trial; NA, not available.

Figure 1 Effects on the primary efficacy outcomes.

Notes: Efficacy outcomes measured cumulatively from baseline, on postrandomization colonoscopy performed within 1 year of discontinuing intervention. Celecoxib at any dose: 400–800 mg/day.

Abbreviations: APC, Adenoma Prevention with Celecoxib trial; PreSAP, Prevention of Colorectal Sporadic Adenomatous Polyps study; Sel/Cel, Selenium and Celecoxib (Sel/Cel) Trial.

Figure 2 Effects of celecoxib at any dose on the safety outcomes.

Abbreviations: APC, Adenoma Prevention with Celecoxib trial; CRC, colorectal cancer; CV, cardiovascular; PreSAP, Prevention of Colorectal Sporadic Adenomatous Polyps Study; Sel/Cel, Selenium and Celecoxib (Sel/Cel) Trial.

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