. 2015 Jul 17;2015(7):CD010952. doi: 10.1002/14651858.CD010952.pub2

2. Characteristics of included post‐hoc studies.

Gossec 2005
Original study: Post hoc analysis of van der Heijde 2005. Comparison: Active drug (etoricoxib 90, etoricoxib 120 and naproxen 500) vs placebo. Analysis: Subgroup analysis in patients with and without chronic peripheral arthritis (defined as painful or swollen peripheral arthritis of > 4 weeks' duration, or a history of peripheral arthritis (anamnestic and based on medical chart), provided that the spine was the primary source of pain). Outcomes: BASDAI question on spine pain, patient global assessment of disease activity (BASFI), BASDAI question on peripheral pain, BASDAI questions on stiffness, BASDAI question on enthesopathy, ASAS 20 responders.
Baseline characteristics
Characteristic			Peripheral arthritis ‐ Yes					Peripheral arthritis ‐ No
Number of participants			115					186
Age (mean (SD))			43.8 (13.9)					43.5 (10.4)
"The two groups appeared to be well balanced, except for a higher percentage of concomitant DMARD and prior corticosteroid use in the group with peripheral arthritis."
Results
Outcome	Peripheral arthritis?		Treatment (N)	Baseline (mean (SD))			Change from BL (mean (95% CI))			P value
Spine pain (VAS, 0 to 100, higher is worse)	Yes Yes No No		Placebo (37) Active drug (117) Placebo (56) Active drug (175)	78.7 (17.3) 77.6 (15.4) 76.2 (13.8) 77.7 (14.5)			‐17.5 (‐24.7 to ‐10.3) ‐34.5 (‐38.6 to ‐30.4)* ‐10.0 (‐15.9 to ‐4.1) ‐42.5 (‐45.8 to ‐39.2)*			*P < 0.05 vs placebo
Peripheral pain (BASDAI) (VAS, 0 to 100, higher is worse)	Yes Yes No No		Placebo (37) Active drug (117) Placebo (56) Active drug (175)	61.8 (27.0) 61.2 (27.5) 45.4 (31.9) 43.5 (31.5)			0.9 (‐5.9 to 7.6) ‐16.4 (‐20.3 to ‐12.6)* ‐5.5 (‐11.0 to ‐0.1) ‐26.6 (‐29.7 to ‐23.5)*			*P < 0.05 vs placebo
Patient global (VAS, to 100, higher is worse)	Yes Yes No No		Placebo (37) Active drug (117) Placebo (56) Active drug (175)	66.5 (21.8) 64.8 (23.3) 62.8 (20.5) 63.4 (20.3)			‐3.3 (‐10.0 to 3.5) ‐22.0 (‐25.7 to ‐18.2)* ‐4.3 (‐9.7 to 1.2) ‐28.0 (‐31.1 to ‐24.9)*			*P < 0.05 vs placebo
BASFI (VAS, 0 to 100, higher is worse)	Yes Yes No No		Placebo (37) Active drug (117) Placebo (56) Active drug (175)	55.2 (29.8) 58.3 (23.8) 53.4 (25.2) 53.7 (23.3)			‐3.5 (‐9.2 to 2.3) ‐14.9 (‐18.2 to ‐11.7)* ‐5.1 (‐9.8 to ‐0.4) ‐20.3 (‐22.9 to ‐17.6)*			*P < 0.05 vs placebo
Morning stiffness (duration + severity) (VAS, 0 to 100, higher is worse)	Yes Yes No No		Placebo (37) Active drug (117) Placebo (56) Active drug (175)	61.8 (26.0) 61.8 (25.4) 65.0 (21.4) 62.6 (23.7)			‐5.7 (‐12.4 to 1.0) ‐24.4 (‐28.1 to ‐20.6)* ‐6.2 (‐11.6 to ‐0.7) ‐28.7 (‐31.8 to ‐25.6)*			*P < 0.05 vs placebo
Outcome	Peripheral arthritis?		Treatment (N)				% reaching ASAS 20			Difference significant?
ASAS 20	Yes Yes No No		Placebo (37) Active drug (117) Placebo (56) Active drug (175)				25% 61%* 25% 71%*			P = 0.001 vs placebo P < 0.001 vs placebo
Discussion: "the combined active drug group provided significant clinical efficacy in AS patients with and without peripheral arthritis. The treatment responses that the authors observed…compared with placebo are in agreement with those seen in other trials...However, the magnitude of these responses was greater in patients without chronic peripheral arthritis or a history of peripheral arthritis. Although a significant difference in treatment effect among those with compared with those without peripheral arthritis was only seen for the primary end point of spinal pain, other end points demonstrated qualitatively similar differences, suggesting an overall difference in response between the two patient subgroups."

Kroon 2012
Original study: Post hoc analysis of Wanders 2005. Comparison: Continuous vs on‐demand NSAID treatment (ketoprofen and celecoxib). Analysis: Relevant subgroups were created by splitting ta‐CRP, ta‐ESR, ta‐BASDAI, ta‐AS‐ DAS‐CRP and ta‐ASDAS‐ESR at predefined values considered as elevated (for the acute phase reactants and representing high and low disease activity for the disease activity measures) ('low' vs 'high'). CRP levels > 5 mg/L and ESR > 12 mm/h were considered elevated; BASDAI > 4 and ASDAS > 2.1 were considered high. These subgroups were further split according to NSAID use (comparing continuous use with on‐demand use). Statistical interactions between subgroups of disease activity and mode of NSAID use, as well as their independent contributory effects, on radiographic progression were tested using multiple regression analysis and logistic regression analysis. Outcomes: BASDAI, inflammation (ESR and CRP), mSASSS, ASDAS‐ESR, ASDAS‐CRP.
Baseline characteristics
		All patients				Patients with complete set of x‐rays
Characteristic		Continuous use (N = 111)	On‐demand use (N = 103)			Continuous use (N = 76)		On‐demand use (N = 74)
Age (mean (SD) years)		38.0 (10.7)	40.1 (10.5)			40.9 (9.8)		37.9 (11.9)
Male (%)		67	72			66		70
Disease duration (mean (SD) years)		11.9 (9.3)	11.0 (9.4)			13.0 (10.2)		10.2 (9.3)
HLA‐B27 (pos. %)		86	87			88		88
"Between‐group differences at baseline were small and negligible… About 73% of the patients in both groups used celecoxib during the entire study period."
Results
Time‐averaged determinant			Outcome		Continuous treatment			On‐demand treatment	P value
CRP		High	dmSASSS (SD)*		0.2 (1.6) (N = 52)			1.7 (2.8) (N = 45)	0.003
			N_prog (%)		7 (13%) (N = 52)			17 (38%) (N = 45)	0.011
		Low	dmSASSS (SD)*		0.9 (1.8) (N = 21)			0.8 (1.1) (N = 25)	0.62
			N_prog (%)		5 (24%) (N = 21)			7 (28%) (N = 25)	0.97
ESR		High	dmSASSS (SD)*		0.9 (1.6) (N = 37)			2.0 (2.4) (N = 35)	0.038
			N_prog (%)		8 (22%) (N = 37)			17 (49%) (N = 35)	0.031
		Low	dmSASSS (SD)*		0.1 (1.8) (N = 35)			0.7 (2.2) (N = 35)	0.03
			N_prog (%)		4 (11%) (N = 35)			7 (20%) (N = 35)	0.51
BASDAI		High	dmSASSS (SD)*		0.1 (1.1) (N = 18)			1.1 (1.6) (N = 24)	0.021
			N_prog (%)		1 (6%) (N = 18)			7 (29%) (N = 24)	0.126
		Low	dmSASSS (SD)*		0.5 (1.8) (N = 58)			1.6 (2.8) (N = 50)	0.015
			N_prog (%)		11 (19%) (N = 58)			19 (38%) (N = 50)	0.047
ASDAS‐CRP		High	dmSASSS (SD)*		0.4 (1.2) (N = 36)			1.9 (2.7) (N = 40)	0.005
			N_prog (%)		4 (11%) (N = 36)			15 (38%) (N = 40)	0.017
		Low	dmSASSS (SD)*		0.4 (2.0) (N = 40)			0.9 (2.1) (N = 34)	0.11
			N_prog (%)		8 (20%) (N = 40)			11 (32%) (N = 34)	0.35
ASDAS‐ESR		High	dmSASSS (SD)*		0.4 (1.3) (N = 30)			1.8 (2.5) (N = 37)	0.006
			N_prog (%)		3 (10%) (N = 30)			15 (41%) (N = 37)	0.012
		Low	dmSASSS (SD)*		0.4 (1.9) (N = 46)			1.1 (2.5) (N = 37)	0.097
			N_prog (%)		9 (20%) (N = 46)			11 (30%) (N = 37)	0.41
* Mean (SD) value of δ modified stoke ankylosing spondylitis spine score (dmSASSS) in this (sub) group, defined as the difference between the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) at month 0 and month 24. N_prog is the number (percentage) of participants in this (sub) group with a progression score on the mSASSS of 2 or more.
Discussion: "continued inflammation in this study represented by ESR, CRP or the combined index ASAS‐ESR and ASDAS‐CRP plays an important role in radiographic progression. … this means we would be able to select patients who may benefit more from continuous use of NSAIDs with regards to radiographic progression… continuous use of NSAIDs can almost completely counteract the negative influence of high ESR on structural damage…The application of continuous therapy with NSAIDs in patients with elevated acute phase reactants may lead to an improved benefit to RR of these drugs, although it remains important to weigh the risk and benefit in individual patients".