Spine Treatment Appraisal Report (STAR): Does Riluzole Improve Outcomes in Patients Undergoing Decompression Surgery for Degenerative Cervical Myelopathy?

Abstract

Fehlings MG, Badhiwala JH, Ahn H, et al. Safety and efficacy of riluzole in patients undergoing decompressive surgery for degenerative cervical myelopathy (CSM-Protect): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial. Lancet Neurol. 2020.

Study Type

Study Quality:

Overall Risk of Bias Rating

Visual Abstract

Why Is This Study an Important Topic?

Degenerative cervical myelopathy represents a non-traumatic form of spinal cord injury for which surgical decompression is often indicated. Many patients end up with substantial residual postoperative disability. Therefore, examining pharmacological therapies that could be combined with surgery to improve long-term patient outcomes is warranted.

What Was the Primary Clinical Question?

In patients who undergo decompression surgery for degenerative cervical myelopathy, does riluzole improve postoperative outcomes?

Study Characteristics

Population:	Included: Adults 18-80 years with symptomatic moderate to severe (mJOA 8-14) degenerative cervical myelopathy scheduled for elective surgery Excluded: Prior surgery for cervical myelopathy; concomitant symptomatic lumbar spinal stenosis; symptoms from spine trauma, neoplasm or infection; pregnant or nursing; hepatic or renal impairment; hx of substance abuse; active malignancy; systemic infection
Treatment:	50 mg riluzole orally 2x/d for 14 days prior to surgery and 28 days after surgery (n = 141, mean age = 59 years, 54% male)
Control:	Placebo taken on the same schedule as the active treatment (n = 149, mean age = 57 years, 57% male)
Outcomes:	Primary: Change in mJOA from baseline to 6-month post op (↓score = ↑ disability/impairment) Secondary: Function via Nurick, NDI; QoL; neck and upper extremity pain; ASIA motor and sensory scores; grip strength
Time:	6 and 12 months.

Results

Result 1. Change in mJOA from baseline.

Result 2. Change in function from baseline.

Result 3. Change in QoL from baseline.

Result 4. Change in neck pain from baseline.

Result 5. Change in ASIA from baseline.

Result 6. Adverse Events. Adverse Events

	Riluzole (n = 147)	Placebo (n = 153)
Death	0	1 (1%)
Pseudarthrosis	3 (2%)	1 (1%)
Hardware failure	3 (2%)	2 (1%)
Worsening myelopathy	13 (9%)	21 (14%)
C5 palsy	9 (6%)	7 (5%)
Neck pain	18 (12%)	29 (19%)
Arm or shoulder pain	17 (12%)	29 (19%)
Arm paresthesia	21 (14%)	18 (12%)
Adjacent segment degeneration	1 (1%)	0
Dural tear	3 (2%)	8 (5%)
Hematoma	3 (2%)	3 (2%)
Deep wound infection	2 (1%)	1 (1%)
Superficial wound infection	5 (3%)	3 (2%)
Dysphagia	18 (12%)	20 (13%)
Hoarseness	4 (3%)	4 (3%)
Arrhythmia	7 (5%)	1 (1%)
Venous thromboembolism	3 (2%)	1 (1%)
Elevated liver enzymes	5 (3%)	3 (2%)
Nausea	10 (7%)	13 (8%)
Dizziness	7 (5%)	6 (4%)
Diarrhea	5 (3%)	3 (2%)
Abdominal pain	2 (1%)	4 (3%)
Pneumonia	0	2 (1%)
Serious adverse events	33 (22%)	29 (19%)

How Will This Affect the Care of My Patients?

Riluzole does not provide an additional benefit to surgical decompression with respect to functional outcomes, QoL, and neurological status. The potential effect of riluzole on pain outcomes warrants further investigation.