Buprenorphine transdermal system compared with placebo reduces interference in functioning for chronic low back pain

Figures & data

Figure 1. Consort flow diagram. Abbreviation: BTDS = buprenorphine transdermal system.

Table I. Patient characteristics at baseline.

Variable	All Patients (N = 541)^a
Age, mean ± SD	49.4 ± 13.0
Sex, number (percentage)
Female	298 (55.1)
Male	243 (44.9)
Average pain NRS, mean ± SD	7.2 ± 1.2
BPI score, mean ± SD
Worst pain	7.7 ± 1.3
Least pain	5.5 ± 2.1
Average pain	6.7 ± 1.4
Pain right now	6.7 ± 1.9
Severity subscale	6.7 ± 1.4
General activity	6.2 ± 2.1
Mood	5.9 ± 2.5
Walking ability	6.0 ± 2.3
Normal work	6.6 ± 2.1
Relations with others	4.8 ± 2.8
Sleeping	6.4 ± 2.4
Enjoyment of life	6.2 ± 2.5
Interference subscale	6.0 ± 2.0

^aSample size varies slightly across variables due to missing data.

Abbreviations: BPI = Brief pain inventory; NRS = Numerical rating scale.

Table II. Comparison of estimated means for BPI Item and subscale scores between BTDS and placebo treatment arms at study end point (Week 12).

BPI Measure	BTDS			Placebo			Mean Difference	Hommel’s Adjusted P^a	Effect Size (d)
	N	Estimated Mean	SE	N	Estimated Mean	SE
Worst pain	166	3.2	0.18	193	4.2	0.17	–1.0	<0.001	0.45
Least pain	166	1.8	0.14	194	2.7	0.13	–0.9	<0.001	0.48
Average pain	164	2.5	0.15	194	3.6	0.14	–1.1	<0.001	0.57
Pain right now	165	2.1	0.17	191	3.2	0.16	–1.1	<0.001	0.53
Severity subscale	165	2.4	0.15	194	3.4	0.14	–1.0	<0.001	0.53
General activity	166	2.2	0.16	194	3.1	0.15	–0.9	<0.001	0.42
Mood	166	1.7	0.16	194	2.7	0.15	–0.9	<0.001	0.46
Walking ability	166	2.2	0.16	193	3.1	0.15	–1.0	<0.001	0.46
Normal work	164	2.3	0.17	194	3.2	0.15	–0.9	<0.001	0.40
Relations with others	166	1.4	0.15	194	2.2	0.14	–0.9	<0.001	0.45
Sleeping	166	2.2	0.17	194	3.1	0.16	–0.9	<0.001	0.43
Enjoyment of life	166	1.8	0.16	194	2.6	0.14	–0.8	<0.001	0.41
Interference subscale	165	2.0	0.14	194	2.8	0.13	–0.9	<0.001	0.47

^aP values are based on ANCOVA models for end-point score with treatment arm as an independent variable and scores from pre-randomization (screening and post–run-in) visits as covariates.

Abbreviations: BPI = Brief Pain Inventory; BTDS = Buprenorphine transdermal system; SE = Standard error around the estimated mean.

Figure 2. Observed means (screening and post–run-in visits) and estimated means (week 4, 8, and 12 visits) from repeated-measures mixed models of Severity (top) and Interference (bottom) subscale scores by treatment arm and visit. Error bars reflect 95% CIs around the mean.

Table III. Comparison of the percentage of patients indicating mild or no interference (ie, Score ≤ 4) on interference subscale items at study end point, controlling for the percentage at screening, between BTDS and placebo treatment arms^a

Interference Item	BTDS		Placebo		Treatment Arm parameter estimate (SE)	OR^b	Hommel’s Adjusted P	95% CI of OR
	Screening (n = 257)	End point (n = 167)	Screening (n = 282)	End point (n = 196)
General activity	21.0%	85.6%	18.4%	71.9%	0.82 (0.28)	2.3	0.0263	1.3–3.9
Mood	25.7%	88.6%	25.2%	77.6%	0.83 (0.30)	2.3	0.0263	1.3–4.2
Walking ability	21.4%	83.2%	25.9%	70.3%	0.77 (0.27)	2.3	0.0263	1.3–3.7
Normal work	13.6%	80.7%	15.6%	69.4%	0.65 (0.25)	1.9	0.0406	1.2–3.1
Relations with others	41.6%	91.0%	41.3%	84.2%	0.71 (0.34)	2.0	0.0991	1.0–4.0
Sleeping	19.5%	82.6%	20.6%	72.4%	0.60 (0.27)	1.8	0.0716	1.1–3.1
Enjoyment of life	22.2%	88.6%	19.1%	76.0%	0.85 (0.30)	2.3	0.0263	1.3–4.2

^aAll models had overall fit of P < 0.001.

^bORs estimated as exp (arm parameter estimate).

Abbreviations: BTDS = Buprenorphine transdermal system; OR = Odds ratio; SE = Standard error around the treatment arm parameter estimate.

Table IV. Comparison between the BTDS and placebo treatment arms of the percentage of treatment responders, based on 30%, 50%, 2-point, or 4-point improvement from screening to end point.

BPI Measure	30% Improvement			50% Improvement			2-Point improvement^a			4-Point improvement^b
	BTDS	Placebo	P^a	BTDS	Placebo	P^c	BTDS	Placebo	P^c	BTDS	Placebo	P^a
Worst pain	80.8%	62.1%	0.001	61.7%	47.2%	0.024	87.4%	70.8%	0.005
Least pain	83.2%	67.2%	0.005	76.6%	55.9%	<0.001	82.6%	66.2%	0.005
Average pain	81.9%	66.2%	0.006	71.7%	47.7%	<0.001	86.1%	71.8%	0.010
Current pain	83.8%	65.8%	0.001	76.0%	53.9%	<0.001	85.6%	71.5%	0.010
Severity subscale	84.3%	65.6%	0.001	69.9%	48.2%	<0.001	83.1%	66.0%	0.005
General activity	79.0%	70.8%	0.269	68.9%	55.4%	0.032				56.9%	40.5%	0.009
Mood	86.8%	74.4%	0.018	80.8%	65.1%	0.007				56.3%	45.1%	0.109
Walking ability	80.2%	68.6%	0.054	71.3%	56.2%	0.018				55.1%	38.1%	0.007
Normal work	80.1%	72.3%	0.288	69.3%	58.5%	0.115				62.0%	47.7%	0.026
Relations with others	82.6%	76.4%	0.462	76.6%	67.2%	0.148				47.9%	30.3%	0.003
Sleeping	82.6%	70.8%	0.042	72.5%	57.9%	0.018				56.3%	44.6%	0.092
Enjoyment of life	88.0%	75.9%	0.018	79.0%	64.1%	0.012				61.1%	48.2%	0.054
Interference subscale	81.9%	71.8%	0.098	71.1%	56.4%	0.018				51.8%	32.6%	0.002

^aMCID for Severity items/subscale.

^bMCID for Interference items/subscale.

^cHommel’s adjusted P values based on X² tests of association.