EBQ:LESS

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Study: Friedly et al.. A randomized trial of epidural glucocorticoid injections for spinal stenosis. The New England journal of medicine 2014. 371:11-21. PMID: 24988555. DOI.

Clinical Question

Among patients with lumbar spinal stenosis and associated pain, does an epidural injection of a glucocorticoid plus lidocaine reduce disability and leg pain at six weeks when compared to an injection of lidocaine alone?

Bottom Line

Among patients with lumbar spinal stenosis and associated pain, epidural injection of a glucocorticoid plus lidocaine is not associated with improvement in disability scores or leg pain at six weeks when compared to injection of lidocaine alone.

Major Points

Epidural administration of glucocorticoids is widely used for symptomatic relief in patients with spinal stenosis though the therapy has not been evaluated in a large, randomized trial. A 2013 Cochrane review classified the existing evidence for epidural injections in this disease as "very low quality" and identified an urgent need for clinical trials.^[1]

The 2014 ARHQ-funded Lumbar Epidural Steroid Injections for Spinal Stenosis (LESS) trial randomized 400 adults ≥50 years old with lumbar spinal stenosis and associated symptoms to epidural administration of lidocaine or a glucocorticoid+lidocaine in a double-blinded fashion. Patients were excluded if they required surgery for spinal instability or if they had significant neurologic or hip pathology. Groups were balanced except for longer symptom duration in glucocorticoid+lidocaine. Both therapies were associated with significant symptom improvement in both primary outcomes at six weeks (which were change on a validated function score and average leg pain in the prior week) though there was no between-group difference for either outcome. The glucocorticoid+lidocaine group experienced improvement in both components of the primary endpoint at three weeks, though the authors note that this was clinically insignificant. When adjusting for duration of pain, the glucocorticoid+lidocaine group experienced a small improvement over the lidocaine group in disability scores at six weeks. As this analysis was post-hoc and the effect was small, it is of dubious clinical significance.

The glucocorticoid+lidocaine group experienced more adverse events, though they were relatively minor and transient.^[2] This group also had greater AM cortisol suppression, suggesting that despite the localized administration of the glucocorticoid, its effects are systemic. The glucocorticoid+lidocaine group had improvement in depressive symptoms and higher satisfaction with treatment than the lidocaine group, which may be related to an unintended effect of the glucocorticoid unrelated to its effects on spinal pathology.^[2]

Though the study was not designed to detect a difference in technique, the glucocorticoid+lidocaine group experienced greater improvement in both components of the primary outcome at three weeks with an interlaminar approach. There was no difference with either approach at six weeks.

While there was no sham group to evaluate for clinical benefit of lidocaine, it is unlikely that this medication provides pain relief or improves disability at a prolonged duration as its half-life is in the scale of hours. As such, the clinical improvement observed from baseline in both groups is likely an effect of regression to the mean and/or efficacy of other unmeasured therapies like PT or non-trial medications.

Design

Multicenter, double-blind, randomized, controlled trial
N=400 (2,224 screened)
- Lidocaine (n=200)
- Glucocorticoid+lidocaine (n=200)
Setting: 16 US centers
Enrollment: 2011-2013
Follow-up: 6 weeks
Analysis: Intention-to-treat
Primary outcomes:
- Roland-Morris Disability Questionnaire
- Average rating of leg pain in prior week

Population

Inclusion Criteria

Age ≥50 years
Pain in low back, buttock and/or lower extremity with standing, walking, and/or spinal extension
- Average pain rating >4 in prior week (out of 10, 10 indicating the worst possible pain)
Roland-Morris Disability Questionnaire (RMDQ) score ≥7 (out of 24, higher score indicates higher physical limitation from back and/or leg pain)
Mild-severe lumbar central canal spinal stenosis by MRI or CT
Lower extremity symptoms of neurogenic claudication
English reading with enough proficiency to complete assessment instruments

Exclusion Criteria

Cognitive impairment preventing informed consent or accurate collection of data
Fibromyalgia
Chronic widespread pain
LE amputation
Parkinson's disease
Head injury
Stroke
"Other neurologic conditions"
Spinal instability requiring surgery
Severe osteoporosis with multiple compression fractures or a fracture at the level of the stenosis
Metastatic cancer
Alcohol or illegal drug abuse
Possible pregnancy or other condition precluding fluoroscopy use
Hip joint pathology or pain with internal hip rotation
Local or systemic infection
Allergy to local anesthetic, steroid, or contrast

Baseline Characteristics

From the lidocaine group. Groups were similar except where specified. Comparisons are lidocaine vs. glucocorticoid+lidocaine.

Demographics: Age 68 years, female 52%, married or living with partner 56%
- Race/ethnicity: White 69%, Black 26%, other 4.5%, Hispanic 3%
- Educational: High school or less 33%, some college 28%, undergraduate completed 16%, professional/graduate completed 23%
- Employment: Full or part time 36%, retired but not disabled 44%, retired and disabled 12%, other 9%
PMH: Current smoker 16%, diabetes on insulin 7.5%
Baseline health data: 30 kg/m²
Lumbar stenosis-specifics:
- Physician rating of severity: Mild 22%, moderate 48%, severe 30%
Back pain-specifics:
- Duration (P=0.02):
  - <3 months: 20.1% vs. 12.0%
  - 3-12 months: 31.2% vs. 29.5%
  - 1-5 years: 21.1% vs. 33.5%
  - >5 years: 27.6% vs. 25.0%
- Rating of pain relief expectation: 7.8 (out of 10, with 10 indicating that the epidural injection would be extremely helpful in resolving the pain)
- RMDQ score: 16
- Numerical pain score: 7.2

Interventions

Patients were randomly assigned to a group:
- Lidocaine
- Glucocorticoid+lidocaine
Injections were either interlaminar or transforaminal and were fluoroscopically-guided

Outcomes

Presented as lidocaine vs. glucocorticoid+lidocaine.

Primary Outcomes

Roland-Morris Disability Questionnaire (RMDQ) at 6 weeks: Out of 24, higher score indicates higher physical limitation from back and/or leg pain.; 12.5 vs. 11.8; Change from baseline: -3.1 vs. -4.2 (adjusted difference -1.0; 95% CI -2.1 to 0.1; P=0.07)

Average rating of leg pain in prior week at 6 weeks: Out of 10, 10 indicating worst pain possible.; 4.6 vs. 4.4; Change from baseline: -2.6 vs. -2.8 (adjusted difference -0.2; 95% CI -0.8 to 0.4; P=0.48)

Secondary Outcomes

RMDQ at 3 weeks: 13.1 vs. 11.7; Change from baseline: -2.6 vs. -4.4 (adjusted difference -1.8; 95% CI -2.8 to -0.9; P<0.001)

Average rating of leg pain in prior week at 3 weeks: 5.0 vs. 4.4; Change from baseline: -2.2 vs. -2.9 (adjusted difference -0.6; 95% CI -1.2 vs. -0.1; P=0.02)

Questionnaires at 6 weeks

BPI: No difference

SSSQ:

Symptoms and physical function: No difference

Satisfaction with treatment: 54% vs. 67% (P=0.01)

EQ-5D: No difference

GAD-7: No difference

PHQ-8: More improvement in depression symptoms with glucocorticoid+lidocaine (average treatment effect -1.0; P=0.007)

Additional Analyses

Post-hoc analysis of the primary outcomes at 6 weeks, adjusted for duration of pain, change since baseline: RMDQ: Greater reduction in glucocorticoid+lidocaine (adjusted difference -1.2; 95% CI -2.3 to -0.1; P=0.03); Average rating of leg pain in prior week: No difference (adjusted difference -0.3; 95% CI -0.9 to 0.3; P=0.32)

Morning cortisol level

At 3 weeks

<3 ug/dL: 0.7% vs. 9.8% (P<0.001)

<10 ug/dL: 42.4% vs. 60.1% (P=0.001)

At 6 weeks

<3 ug/dL: 0% vs. 3.3% (P=0.06)

<10 ug/dL: 37.8% vs. 53.3% (P=0.01)

Glucocorticoids used: Celestone: 30.0% vs. 31.0%; Depomedrol: 29.0% vs. 30.5%; Dexamethasone: 17.0% vs. 17.0%; Kenalog: 24.0% vs. 21.5%

Transforaminal approach: 30.5% vs. 28.5%; Bilateral injections: 50.8% vs. 42.1%; Multilevel injections: 31.1% vs. 24.6%

Subgroup Analysis

For subgroup analyses, the authors defined statistical significance as <0.025.

Change in RMDQ score by approach

Interlaminar

Week 3: -2.9 vs. -5.4 (adjusted difference -2.5; 95% CI -3.7 to -1.3; P<0.001)

Week 6: -3.3 vs. -4.8 (adjusted difference -1.4; 95% CI -2.8 to -0.1; P=0.04)

Transforaminal

Week 3: -1.8 vs. -1.8 (adjusted difference -0.1; 95% CI -1.7 to 1.6; P=0.94)

Week 6: -2.6 vs. -2.4 (adjusted difference -0.3; 95% CI -1.9 to 1.8; P=0.95)

Change in average leg pain in prior week

Interlaminar

Week 3: -2.4 vs. -3.2 (adjusted difference -0.9; 95% CI -1.5 to -0.3; P=0.005)

Week 6: -2.8 vs. -3.1 (adjusted difference -0.3; 95% CI -1.0 to 0.4; P=0.37)