Why carry out this study?
|
Mirogabalin, a potent selective ligand of the α2δ subunit of voltage-gated Ca2+ channels, has been approved for use in Japan, Korea, and Taiwan. |
The efficacy of mirogabalin in improving peripheral neuropathic pain in patients with lumbar spinal stenosis (LSS) has been previously reported, but the number of studied cases is limited, and its efficacy and safety have not been fully investigated. |
We conducted a multicenter, randomized, open-label, parallel group, interventional study to assess the efficacy and safety of mirogabalin as an add-on in LSS patients taking non-steroidal anti-inflammatory drugs (NSAIDs) compared with those taking NSAIDs alone. |
What was learned from the study?
|
Mirogabalin as an add-on to NSAIDs led to clinically meaningful improvement in pain intensity (visual analog scale score) and quality of life (EuroQol five-dimensional descriptive system and Patient Global Impression of Change questionnaire) with greater improvements than with NSAIDs alone in LSS patients. |
Mirogabalin as an add-on in LSS patients treated with NSAIDs was generally well tolerated. |
Mirogabalin as an add-on to NSAIDs may be an option for LSS patients who cannot achieve adequate pain control with NSAIDs only. |
Introduction
Methods
Trial Design
Patients
Endpoints
Subgroup Analysis
Statistical Analysis
Sample Size
Results
Patients
Characteristics | Mirogabalin and NSAIDs (n = 110) | NSAIDs (n = 104) |
---|---|---|
Age, years ≥ 65 years | 67.8 ± 11.3 74 (67.3) | 70.9 ± 9.2 78 (75.0) |
Sex | ||
Male | 50 (45.5) | 53 (51.0) |
Female | 60 (54.5) | 51 (49.0) |
Body weight, kg < 60 | 63.9 ± 14.1 44 (40.0) | 62.0 ± 12.9 42 (40.4) |
VAS score at enrollment, mm < 60 ≥ 60 | 63.8 ± 13.4 51 (46.4) 59 (53.6) | 62.8 ± 13.9 49 (47.1) 55 (52.9) |
SPDQ score < 0 ≥ 0 | 6.8 ± 9.3a 20 (18.5)a 88 (81.5)a | 7.8 ± 9.8 19 (18.3) 85 (81.7) |
SF-SPDQ score < 0 ≥ 0 | 10.2 ± 9.0b 12 (11.0)b 97 (89.0)b | 11.2 ± 10.0 13 (12.5) 91 (87.5) |
CrCL at enrollment, mL/minc ≥ 60 30 to < 60 | 81.5 ± 35.3 80 (72.7) 30 (27.3) | 70.7 ± 23.3 69 (66.3) 35 (33.7) |
Duration of radicular type of LSS, months Median (Q1, Q3) ≥ 6 | 23.1 ± 30.8 9.0 (4.0, 28.0) 76 (69.1) | 27.1 ± 38.9 11.0 (5.0, 30.5) 71 (68.3) |
Duration of leg pain, months Median (Q1, Q3) | 28.3 ± 34.3 12.0 (7.0, 35.0) | 28.5 ± 40.0 13.0 (5.0, 33.0) |
Symptoms of radicular type of LSS | ||
Pain | 19 (17.3) | 21 (20.2) |
Numbness | 0 (0.0) | 0 (0.0) |
Pain and numbness | 91 (82.7) | 83 (79.8) |
Concomitantly restricted drugsd Rimaprost alphadex (oral) Ketoprofen (topical) Loxoprofen sodium hydrate (topical) | 62 (56.4) 25 (22.7) 14 (12.7) 11 (10.0) | 52 (50.0) 21 (20.2) 9 (8.7) 18 (17.3) |
Rescue medication (acetaminophen) | 66 (60.0) | 82 (78.8) |
NSAIDs (oral) | ||
Celecoxib Loxoprofen sodium hydrate Etodolac Diclofenac sodium Meloxicam Thiaramide hydrochloride Zaltoprofen Lornoxicam | ||
62 (56.4) 36 (32.7) 4 (3.6) 4 (3.6) 1 (0.9) 1 (0.9) 1 (0.9) 1 (0.9) | 60 (57.7) 35 (33.7) 4 (3.8) 1 (1.0) 4 (3.8) 0 (0.0) 0 (0.0) 0 (0.0) | |
Past medical history Cervical spondylosis Ossification of the posterior longitudinal ligament Intervertebral disc herniation Lumbar spinal canal stenosis Spondylolysis/spondylolisthesis Osteoporotic compression fracture Scoliosis Spinal cord tumors | 9 (8.2) 3 (2.7) 0 (0.0) 4 (3.6) 2 (1.8) 1 (0.9) 2 (1.8) 0 (0.0) 0 (0.0) | 18 (17.3) 4 (3.8) 2 (1.9) 5 (4.8) 4 (3.8) 1 (1.0) 3 (2.9) 2 (1.9) 2 (1.9) |
Complications Complications of orthopedic diseasese Diabetes Stroke Hypertension Hyperlipidemia Cervical spondylosis Posterior longitudinal ligament ossification Rheumatoid arthritis Herniated intervertebral disc Spondylolysis/spondylolisthesis Osteoporotic compression fracture Scoliosis | 82 (74.5) 37 (33.6) 17 (15.5) 3 (2.7) 55 (50.0) 42 (38.2) 5 (4.5) 1 (0.9) 4 (3.6) 13 (11.8) 14 (12.7) 1 (0.9) 7 (6.4) | 79 (76.0) 26 (25.0) 24 (23.1) 2 (1.9) 59 (56.7) 33 (31.7) 3 (2.9) 0 (0.0) 4 (3.8) 8 (7.7) 12 (11.5) 0 (0.0) 2 (1.9) |
History of spine surgery Cervical vertebrae Thoracic vertebrae | 2 (1.8) 2 (1.8) 0 (0.0) | 4 (3.8) 3 (2.9) 1 (1.0) |
Compliance with the package insert | ||
Compliant Non-compliant | 82 (74.5) 28 (25.5) | 100 (96.2) 4 (3.8) |
Efficacy
Parameter | Mirogabalin and NSAIDs (n = 85) | NSAIDs (n = 75) |
---|---|---|
Change in VAS score from baseline, mm | ||
LS mean ± SE | − 24.1 ± 2.8 | − 14.2 ± 3.0 |
95% CI | − 29.6, − 18.6 | − 20.2, − 8.3 |
P value vs. baselinea | < 0.0001 | < 0.0001 |
Difference in LS mean change in VAS score, mm | ||
LS mean ± SE | − 9.9 ± 4.1 | – |
95% CI | − 18.0, − 1.8 | – |
P value vs. NSAIDsa | 0.0174 | – |
Parameter | Mirogabalin and NSAIDs (n = 85) | NSAIDs (n = 75) | ||
---|---|---|---|---|
Baseline | Week 12 | Baseline | Week 12 | |
EQ-5D-5L scorea | ||||
Mean ± SD | 0.6525 ± 0.1555 | 0.7312 ± 0.1587 | 0.7008 ± 0.1534 | 0.7267 ± 0.1660 |
Median (Q1, Q3) | 0.6848 (0.5571, 0.7589) | 0.7589 (0.6361, 0.8307) | 0.7315 (0.5925, 0.8228) | 0.7566 (0.6412, 0.8479) |
Min, Max | 0.269, 1.000 | 0.209, 1.000 | 0.245, 1.000 | 0.208, 1.000 |
Change in EQ-5D-5L scorea | ||||
Mean ± SD | – | 0.0787 ± 0.1641 | – | 0.0259 ± 0.1497 |
Mean difference (95% CI)a | – | 0.0529 (0.0036, 0.1022) | – | – |
P value vs. NSAIDsb | – | 0.0357 | – | – |
Mirogabalin and NSAIDs (n = 84) | NSAIDs (n = 74) | |
---|---|---|
1. Very much improved | 9 (10.7) | 4 (5.4) |
2. Much improved | 31 (36.9) | 20 (27.0) |
3. Minimally improved | 24 (28.6) | 13 (17.6) |
4. No change | 13 (15.5) | 27 (36.5) |
5. Minimally worse | 3 (3.6) | 8 (10.8) |
6. Much worse | 4 (4.8) | 2 (2.7) |
7. Very much worse | 0 (0.0) | 0 (0.0) |
PGIC (score ≤ 3) | 64 (76.2) | 37 (50.0) |
Difference | 26.2 | – |
95% CI | 11.6, 40.8 | – |
P value vs. NSAIDsa | 0.0006 | – |
PGIC (score ≤ 2) | 40 (47.6) | 24 (32.4) |
Difference | 15.2 | – |
95% CI | 0.1, 30.3 | – |
P value vs. NSAIDsa | 0.0523 | – |
Safety
Safety analysis set | Mirogabalin and NSAIDs (n = 110) | NSAIDs (n = 106) |
---|---|---|
Overall TEAEs | 67 (60.9) | 15 (14.2) |
Somnolence | 33 (30.0) | 0 (0.0) |
Dizziness | 28 (25.5) | 1 (0.9) |
Oedema peripheral | 6 (5.5) | 0 (0.0) |
Constipation | 6 (5.5) | 0 (0.0) |
Unpleasant sensation in the abdomen | 2 (1.8) | 4 (3.8) |
Serious TEAEs | 0 (0.0) | 1 (0.9) |
Discontinuation due to TEAEs | 9 (8.2) | 0 (0.0) |
Overall ADRs | 63 (57.3) | 4 (3.8) |
Somnolence | 33 (30.0) | 0 (0.0) |
Dizziness | 28 (25.5) | 1 (0.9) |
Oedema peripheral | 6 (5.5) | 0 (0.0) |
Constipation | 6 (5.5) | 0 (0.0) |
Serious ADRs | 0 (0.0) | 0 (0.0) |
Discontinuation due to ADRs | 9 (8.2) | 0 (0.0) |