Effectiveness of pregabalin for treatment of chronic cervical radiculopathy with upper limb radiating pain: an 8-week, multicenter prospective observational study in Japanese primary care settings

Figures & data

Figure 1 Patient disposition.

Abbreviations: AE, adverse event; NSAIDs, non-steroidal anti-inflammatory drugs.

Table 1 Baseline demographic and clinical characteristics

Characteristic	Pregabalin (n=145)	Usual care^a (n=224)	P-value^b
Sex, n (%)			<0.001
Male	77 (53.1)	68 (30.4)
Female	68 (46.9)	156 (69.6)
Age group, years, n (%)			<0.001
<65	95 (65.5)	83 (37.1)
65–74	19 (13.1)	52 (23.2)
≥75	31 (21.4)	89 (39.7)
Age, years			<0.001
Mean±SD	58.3±15.9	66.4±15.8
Median (min, max)	59.0 (22, 88)	70.0 (20, 90)
Primary diagnosis of pain			0.177
Cervical spondylotic myelopathy	7 (4.8)	7 (3.1)
Cervical spondylotic radiculopathy	85 (58.6)	111 (49.6)
Cervical disk herniation	14 (9.7)	27 (12.1)
Ossification of posterior longitudinal ligament	0	0
Cervical spondylosis	1 (0.7)	0
Others	38 (26.2)	79 (35.3)
Duration of pain (months)			0.098
Mean±SD	28.8±38.6	37.1±50.9
Median (min, max)	12.0 (2, 183)	16.5 (3, 395)
PRSIS			0.021
Mean±SD	3.3±2.4	2.8±2.0
Median (min, max)	2.0 (1, 10)	2.0 (1, 9)
Pain NRS			0.005
Mean±SD	6.1±1.2	5.8±1.1
Median (min, max)	6.0 (5, 10)	5.0 (5, 10)
NDI			0.728
Mean±SD	30.9±14.6	31.4±13.1
Median (min, max)	28.0 (0, 76)	29.0 (0, 78)
EQ-5D-5L
QoL Score			0.539
Mean±SD	0.7±0.2	0.7±0.1
Median (min, max)	0.7 (0.1, 0.9)	0.7 (0.2, 1.0)
VAS			0.789
Mean±SD	52.8±17.6	52.4±13.3
Median (min, max)	50.0 (0, 90)	50.0 (10, 95)
Pain treatment prior to study start, n (%)
Any drug	145 (100)	224 (100)	-
NSAIDs	135 (93.1)	200 (89.3)	0.216
Antidepressants^c	8 (5.5)	6 (2.7)	0.163
Weak opioids^d	6 (4.1)	10 (4.5)	0.880
Other antiepileptics^c	1 (0.7)	0	0.213
Potent opioids^d	0	0	-
Other drug^e	49 (33.8)	63 (28.1)	0.247

Notes: Scales are defined in full in the methods. ^a“Usual care” with conventional analgesic care or other treatment(s) was based on physician’s best clinical judgment. ^bt-test and chi-square test for continuous and categorical data, respectively. ^cUsed for chronic cervical pain. ^dWeak opioids were tramadol, tramadol/acetaminophen, buprenorphine, pentazocine and codeine; potent opioids were morphine, oxycodone and fentanyl. ^eAcetaminophen taken alone is included within “other” drugs.

Abbreviations: EQ-5D-5L, EuroQol five dimensions five level; NDI, Neck Disability Index; NRS, numerical rating scale; NSAIDs, non-steroidal anti-inflammatory drugs; PRSIS, Pain-Related Sleep Interference Scale; QoL, quality of life; SD, standard deviation; VAS, visual analog scale.

Figure 2 Change from baseline in weekly PRSIS at weeks 4 and 8.

Abbreviations: LS, least squares; PRSIS, Pain-Related Sleep Interference Scale; SE, standard error.

Figure 3 Change from baseline in weekly NRS for pain at weeks 4 and 8 (A), and proportions of patients at week 8 reporting clinically relevant improvements in pain (LOCF) (B).

Abbreviations: LOCF, last observation carried forward; LS, least squares; NRS, numerical rating scale; SE, standard error.

Figure 4 Global impression of change at week 8 from the perspectives of (A) the clinician, assessed using the CGIC, and (B) the patient, assessed using the PGIC.

Abbreviations: CGIC, Clinical Global Impression of Change; PGIC, Patient Global Impression of Change.

Table 2 Neck Disability Index and EuroQoL five dimensions five levels

Week	Treatment	n^a	LS		Treatment comparison (pregabalin vs usual care)
			mean change	SE	Difference	95% CI	P–value
NDI
4	Pregabalin	131	–5.652	0.744	–4.702	(–6.574, –2.830)	<0.001
	Usual care^b	207	–0.949	0.593
8/Endpoint	Pregabalin	121	–8.484	0.809	–5.974	(–8.004, –3.943)	<0.001
	Usual care^b	194	–2.510	0.641
EQ-5D-5L QoL Score
4	Pregabalin	131	0.048	0.009	0.037	(0.015, 0.059)	0.001
	Usual care^b	207	0.011	0.007
8/Endpoint	Pregabalin	121	0.078	0.009	0.039	(0.016, 0.061)	0.001
	Usual care^b	193	0.040	0.007
EQ-5D-5L VAS
4	Pregabalin	127	5.822	1.148	4.461	(1.584, 7.337)	0.002
	Usual care^b	205	1.361	0.905
8/Endpoint	Pregabalin	117	10.780	1.338	8.269	(4.923, 11.615)	<0.001
	Usual care^b	191	2.512	1.050

Notes: ^aOf the patients in the Full Analysis Set, only evaluable patients of this endpoint, for which definition was prespecified in the study protocol, were contributed. ^b“Usual care” with conventional analgesic care or other treatment(s) was based on physician’s best clinical judgment.

Abbreviations: CI, confidence interval; EQ-5D-5L, EuroQol five dimensions five level; LS, least squares; NDI, Neck Disability Index; SE, standard error; VAS, visual analog scale.

Table 3 Adverse events (Safety Analysis Set)^a

	Pregabalin (n=145)	Usual care^b (n=224)
All-causality AEs	n (%)	n (%)
Number of AEs	59	65
Patients with AEs	42 (29.0)	48 (21.4)
Patients with SAEs	2 (1.4)	1 (0.4)
Patients discontinued due to AE	7 (4.8)	0
Most common AEs^c
Dizziness	14(9.7)	1 (0.4)
Nasopharyngitis	6 (4.1)	0
Somnolence	6 (4.1)	0
Bronchitis	0	5 (2.2)
Treatment-related AEs
Number of AEs	25	0
Patients with AEs	22 (15.2)	0
Patients with SAEs	0	0
Most common AEs^c
Dizziness	14 (9.7)	0
Somnolence	6 (4.1)	0

Notes: ^aThe Safety Analysis Set includes all patients who received at least one dose of the pregabalin or control treatment(s) and had at least one post-baseline evaluable safety assessment. ^b“Usual care” with conventional analgesic care or other treatment(s) was based on physician’s best clinical judgment. ^cMost common AEs defined as occurring in >2% of the patients in any treatment group.

Abbreviations: AE, adverse event; SAE; serious adverse event.

Table S1 Concomitant medications used through the study period for patients in the pregabalin and usual care treatment arms

	Day −1^a	Day 1^b	Day 8	Day 15	Day 22	Day 29	Day 36	Day 43	Day 50	Day 57	End of Study^c
Pregabalin	n=145	n=145	n=142	n=141	n=140	n=137	n=135	n=135	n=128	n=62	n=145
Patients, n (%)
Any drug except for pregabalin	143 (98.6)	115 (79.3)	110 (77.5)	106 (75.2)	105 (75.0)	104 (75.9)	101 (74.8)	99 (73.3)	92 (71.9)	52 (83.9)	107 (73.8)
NSAIDs	128 (88.3)	102 (70.3)	97 (68.3)	94 (66.7)	93 (66.4)	92 (67.2)	91 (67.4)	88 (65.2)	83 (64.8)	45 (72.6)	96 (66.2)
Antidepressant^d	7 (4.8)	5 (3.4)	5 (3.5)	5 (3.5)	6 (4.3)	5 (3.6)	5 (3.7)	5 (3.7)	4 (3.1)	3 (4.8)	5 (3.4)
Antiepileptic^d	1 (0.7)	1 (0.7)	1 (0.7)	1 (0.7)	1 (0.7)	1 (0.7)	1 (0.7)	1 (0.7)	1 (0.8)	1 (1.6)	1 (0.7)
Weak opioid^e	6 (4.1)	4 (2.8)	4 (2.8)	4 (2.8)	4 (2.9)	3 (2.2)	3 (2.2)	3 (2.2)	3 (2.3)	1 (1.6)	3 (2.1)
Potent opioid^e	0	0	0	0	0	0	0	0	0	0	0
Other drug^f	40 (27.6)	40 (27.6)	35 (24.6)	35 (24.8)	33 (23.6)	35 (25.5)	32 (23.7)	29 (21.5)	28 (21.9)	20 (32.3)	33 (22.8)
Usual Care^g	n=224^a	n=224^b	n=222	n=222	n=219	n=218	n=217	n=215	n=201	n=104	n=224^c
Patients, n (%)
Any drug	223 (99.6)	223 (99.6)	220 (99.1)	220 (99.1)	217 (99.1)	215 (98.6)	214 (98.6)	212 (98.6)	200 (99.5)	103 (99.0)	223 (99.6)
NSAIDs	199 (88.8)	200 (89.3)	198 (89.2)	198 (89.2)	195 (89.0)	193 (88.5)	193 (88.9)	192 (89.3)	181 (90.0)	88 (84.6)	200 (89.3)
Antidepressant^d	6 (2.7)	6 (2.7)	6 (2.7)	6 (2.7)	6 (2.7)	6 (2.8)	6 (2.8)	6 (2.8)	6 (3.0)	5 (4.8)	6 (2.7)
Antiepileptic^d	0	0	0	0	0	0	0	0	0	0	0
Weak opioid^e	9 (4.0)	11 (4.9)	11 (5.0)	11 (5.0)	11 (5.0)	11 (5.0)	10 (4.6)	10 (4.7)	9 (4.5)	4 (3.8)	10 (4.5)
Potent opioid^e	0	0	0	0	0	0	0	0	0	0	0
Other drug^f	57 (25.4)	75 (33.5)	71 (32.0)	74 (33.3)	72 (32.9)	75 (34.4)	72 (33.2)	70 (32.6)	69 (34.3)	35 (33.7)	75 (33.5)

Notes: ^aDay –1 was defined as the day before “Day 1”. ^bDay 1 for pregabalin was the first day of treatment, for usual care Day 1 was the day of first PRSIS assessment (as usual care could be present before joining the study). ^cLast day of study medication. ^dUsed for chronic cervical pain. ^eWeak opioids were tramadol, tramadol/acetaminophen, buprenorphine, pentazocine and codeine; potent opioids were morphine, oxycodone and fentanyl. ^fAcetaminophen taken alone is included within “other” drugs. ^g“Usual care” with conventional analgesic care or other treatment(s) was based on physician’s best clinical judgment.

Abbreviation: NSAIDs, non-steroidal anti-inflammatory drugs.